Protocol Index	

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OP RSH PRO00037748 ABDELRAHIM CO44668 BOTH ARMS	

Types:      Research Oncology Treatment
Synonyms:  PRO00037748, ABDELRAHIM, CO44668, LIVER, HEPATIC, ATEZOLIZUMAB, BEVACIZUMAB, TIRAGOLUMAB, IMBRAVE152

Cycle 1	Repeat 1 time	Cycle length: 21 days	C1 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T3	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T4, FREE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	Not applicable for a site that has not been granted approval for RBR sampling. Performed only for participants at participating sites who have provided written informed consent to participate
		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 2	Repeat 1 time	Cycle length: 21 days	C2 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	Not applicable for a site that has not been granted approval for RBR sampling. Performed only for participants at participating sites who have provided written informed consent to participate
		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Baseline
  	ONC NURSING COMMUNICATION 104	Interval: --	Occurrences: --	Comments:	Participants will undergo tumor assessments at baseline, every 6 weeks (± 1 week) for the first 54 weeks following treatment initiation, and every 9 weeks (± 1 weeks) thereafter, regardless of dose delays, except in the case of participants who continue treatment after radiographic disease progression; such participants will undergo tumor assessments every 6 weeks (? 1 week) until loss of clinical benefit as determined by the investigator. Thus, tumor assessments are to continue according to schedule in participants who discontinue treatment for reasons other than loss of clinical benefit, even if they start new non-protocol-specified anti-cancer therapy.
All measurable and/or evaluable lesions identified at baseline should be re-assessed at subsequent tumor evaluations according to the tumor assessment schedule described above (see footnote "o"). Brain metastases identified at baseline that have been treated with radiotherapy or surgery will not be considered measurable or evaluable unless there is suspected disease progression in the brain (i.e., the participant becomes symptomatic). Thus, subsequent head scans are not required unless clinically indicated. The same radiographic procedures used to assess disease sites at screening should be used for subsequent tumor assessments (e.g., the same contrast protocol for CT scans).
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 3	Repeat 1 time	Cycle length: 21 days	C3 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	Not applicable for a site that has not been granted approval for RBR sampling. Performed only for participants at participating sites who have provided written informed consent to participate
		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 4	Repeat 1 time	Cycle length: 21 days	C4 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	Not applicable for a site that has not been granted approval for RBR sampling. Performed only for participants at participating sites who have provided written informed consent to participate
		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Baseline
  	ONC NURSING COMMUNICATION 104	Interval: --	Occurrences: --	Comments:	Participants will undergo tumor assessments at baseline, every 6 weeks (± 1 week) for the first 54 weeks following treatment initiation, and every 9 weeks (± 1 weeks) thereafter, regardless of dose delays, except in the case of participants who continue treatment after radiographic disease progression; such participants will undergo tumor assessments every 6 weeks (? 1 week) until loss of clinical benefit as determined by the investigator. Thus, tumor assessments are to continue according to schedule in participants who discontinue treatment for reasons other than loss of clinical benefit, even if they start new non-protocol-specified anti-cancer therapy.
All measurable and/or evaluable lesions identified at baseline should be re-assessed at subsequent tumor evaluations according to the tumor assessment schedule described above (see footnote "o"). Brain metastases identified at baseline that have been treated with radiotherapy or surgery will not be considered measurable or evaluable unless there is suspected disease progression in the brain (i.e., the participant becomes symptomatic). Thus, subsequent head scans are not required unless clinically indicated. The same radiographic procedures used to assess disease sites at screening should be used for subsequent tumor assessments (e.g., the same contrast protocol for CT scans).
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 5	Repeat 1 time	Cycle length: 21 days	C5D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T3	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T4, FREE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --		  	HEPATITIS B VIRUS (HBV), QUANTITATIVE, DNA (ABBOTT REALTIME)	Interval: --	Occurrences: --	Comments:	Participants without a prior positive HIV test result will undergo an HIV test, unless not permitted per local regulations. Participants will be tested for HbsAg, total HbcAb, and HCV antibody. If a participant has a positive HbsAg test and/or a positive total HbcAb test at screening, quantitative HbsAg and an HBV DNA test should be performed at screening. If local quantitative HbsAg test is not available, a qualitative HbsAg followed by quantitative HBV DNA can be performed as an alternative. Study treatment and procedures may proceed while HBV DNA is being processed, but results should be reviewed by the investigator as soon as they are available. If HBV DNA increases to greater than or equal to  500 IU/mL, consultation with a hepatologist or gastroenterologist with specialty in HBV is recommended. The Medical Monitor is available to advise as needed. If a participant has a positive HCV antibody test, an HCV RNA test must also be performed to determine if the participant has an HCV 
infection. Participants will also be tested for the following: (1) EBV VCA IgM, (2) EBV VCA IgG or EBNA IgG, and (3) EBV PCR (only if clinically indicated).
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA 

Participants without a prior positive HIV test result will undergo an HIV test, unless not permitted per local regulations. Participants will be tested for HbsAg, total HbcAb, and HCV antibody. If a participant has a positive HbsAg test and/or a positive total HbcAb test at screening, quantitative HbsAg and an HBV DNA test should be performed at screening. If local quantitative HbsAg test is not available, a qualitative HbsAg followed by quantitative HBV DNA can be performed as an alternative. Study treatment and procedures may proceed while HBV DNA is being processed, but results should be reviewed by the investigator as soon as they are available. If HBV DNA increases to greater than or equal to 500 IU/mL, consultation with a hepatologist or gastroenterologist with specialty in HBV is recommended. The Medical Monitor is available to advise as needed. If a participant has a positive HCV antibody test, an HCV RNA test must also be performed to determine if the participant has an HCV 
infection. Participants will also be tested for the following: (1) EBV VCA IgM, (2) EBV VCA IgG or EBNA IgG, and (3) EBV PCR (only if clinically indicated).
			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 6	Repeat 1 time	Cycle length: 21 days	C6 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Baseline
  	ONC NURSING COMMUNICATION 104	Interval: --	Occurrences: --	Comments:	Participants will undergo tumor assessments at baseline, every 6 weeks (± 1 week) for the first 54 weeks following treatment initiation, and every 9 weeks (± 1 weeks) thereafter, regardless of dose delays, except in the case of participants who continue treatment after radiographic disease progression; such participants will undergo tumor assessments every 6 weeks (? 1 week) until loss of clinical benefit as determined by the investigator. Thus, tumor assessments are to continue according to schedule in participants who discontinue treatment for reasons other than loss of clinical benefit, even if they start new non-protocol-specified anti-cancer therapy.
All measurable and/or evaluable lesions identified at baseline should be re-assessed at subsequent tumor evaluations according to the tumor assessment schedule described above (see footnote "o"). Brain metastases identified at baseline that have been treated with radiotherapy or surgery will not be considered measurable or evaluable unless there is suspected disease progression in the brain (i.e., the participant becomes symptomatic). Thus, subsequent head scans are not required unless clinically indicated. The same radiographic procedures used to assess disease sites at screening should be used for subsequent tumor assessments (e.g., the same contrast protocol for CT scans).
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 7	Repeat 1 time	Cycle length: 21 days	C7 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 8	Repeat 1 time	Cycle length: 21 days	C8 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	Not applicable for a site that has not been granted approval for RBR sampling. Performed only for participants at participating sites who have provided written informed consent to participate
		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Baseline
  	ONC NURSING COMMUNICATION 104	Interval: --	Occurrences: --	Comments:	Participants will undergo tumor assessments at baseline, every 6 weeks (± 1 week) for the first 54 weeks following treatment initiation, and every 9 weeks (± 1 weeks) thereafter, regardless of dose delays, except in the case of participants who continue treatment after radiographic disease progression; such participants will undergo tumor assessments every 6 weeks (? 1 week) until loss of clinical benefit as determined by the investigator. Thus, tumor assessments are to continue according to schedule in participants who discontinue treatment for reasons other than loss of clinical benefit, even if they start new non-protocol-specified anti-cancer therapy.
All measurable and/or evaluable lesions identified at baseline should be re-assessed at subsequent tumor evaluations according to the tumor assessment schedule described above (see footnote "o"). Brain metastases identified at baseline that have been treated with radiotherapy or surgery will not be considered measurable or evaluable unless there is suspected disease progression in the brain (i.e., the participant becomes symptomatic). Thus, subsequent head scans are not required unless clinically indicated. The same radiographic procedures used to assess disease sites at screening should be used for subsequent tumor assessments (e.g., the same contrast protocol for CT scans).
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 9	Repeat 1 time	Cycle length: 21 days	C9 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T3	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T4, FREE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --		  	HEPATITIS B VIRUS (HBV), QUANTITATIVE, DNA (ABBOTT REALTIME)	Interval: --	Occurrences: --	Comments:	Participants without a prior positive HIV test result will undergo an HIV test, unless not permitted per local regulations. Participants will be tested for HbsAg, total HbcAb, and HCV antibody. If a participant has a positive HbsAg test and/or a positive total HbcAb test at screening, quantitative HbsAg and an HBV DNA test should be performed at screening. If local quantitative HbsAg test is not available, a qualitative HbsAg followed by quantitative HBV DNA can be performed as an alternative. Study treatment and procedures may proceed while HBV DNA is being processed, but results should be reviewed by the investigator as soon as they are available. If HBV DNA increases to greater than or equal to  500 IU/mL, consultation with a hepatologist or gastroenterologist with specialty in HBV is recommended. The Medical Monitor is available to advise as needed. If a participant has a positive HCV antibody test, an HCV RNA test must also be performed to determine if the participant has an HCV 
infection. Participants will also be tested for the following: (1) EBV VCA IgM, (2) EBV VCA IgG or EBNA IgG, and (3) EBV PCR (only if clinically indicated).
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA 

Participants without a prior positive HIV test result will undergo an HIV test, unless not permitted per local regulations. Participants will be tested for HbsAg, total HbcAb, and HCV antibody. If a participant has a positive HbsAg test and/or a positive total HbcAb test at screening, quantitative HbsAg and an HBV DNA test should be performed at screening. If local quantitative HbsAg test is not available, a qualitative HbsAg followed by quantitative HBV DNA can be performed as an alternative. Study treatment and procedures may proceed while HBV DNA is being processed, but results should be reviewed by the investigator as soon as they are available. If HBV DNA increases to greater than or equal to 500 IU/mL, consultation with a hepatologist or gastroenterologist with specialty in HBV is recommended. The Medical Monitor is available to advise as needed. If a participant has a positive HCV antibody test, an HCV RNA test must also be performed to determine if the participant has an HCV 
infection. Participants will also be tested for the following: (1) EBV VCA IgM, (2) EBV VCA IgG or EBNA IgG, and (3) EBV PCR (only if clinically indicated).
			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 10	Repeat 1 time	Cycle length: 21 days	C10 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Baseline
  	ONC NURSING COMMUNICATION 104	Interval: --	Occurrences: --	Comments:	Participants will undergo tumor assessments at baseline, every 6 weeks (± 1 week) for the first 54 weeks following treatment initiation, and every 9 weeks (± 1 weeks) thereafter, regardless of dose delays, except in the case of participants who continue treatment after radiographic disease progression; such participants will undergo tumor assessments every 6 weeks (? 1 week) until loss of clinical benefit as determined by the investigator. Thus, tumor assessments are to continue according to schedule in participants who discontinue treatment for reasons other than loss of clinical benefit, even if they start new non-protocol-specified anti-cancer therapy.
All measurable and/or evaluable lesions identified at baseline should be re-assessed at subsequent tumor evaluations according to the tumor assessment schedule described above (see footnote "o"). Brain metastases identified at baseline that have been treated with radiotherapy or surgery will not be considered measurable or evaluable unless there is suspected disease progression in the brain (i.e., the participant becomes symptomatic). Thus, subsequent head scans are not required unless clinically indicated. The same radiographic procedures used to assess disease sites at screening should be used for subsequent tumor assessments (e.g., the same contrast protocol for CT scans).
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 11	Repeat 1 time	Cycle length: 21 days	C11 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 12	Repeat 1 time	Cycle length: 21 days	C12 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	Not applicable for a site that has not been granted approval for RBR sampling. Performed only for participants at participating sites who have provided written informed consent to participate
		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Baseline
  	ONC NURSING COMMUNICATION 104	Interval: --	Occurrences: --	Comments:	Participants will undergo tumor assessments at baseline, every 6 weeks (± 1 week) for the first 54 weeks following treatment initiation, and every 9 weeks (± 1 weeks) thereafter, regardless of dose delays, except in the case of participants who continue treatment after radiographic disease progression; such participants will undergo tumor assessments every 6 weeks (? 1 week) until loss of clinical benefit as determined by the investigator. Thus, tumor assessments are to continue according to schedule in participants who discontinue treatment for reasons other than loss of clinical benefit, even if they start new non-protocol-specified anti-cancer therapy.
All measurable and/or evaluable lesions identified at baseline should be re-assessed at subsequent tumor evaluations according to the tumor assessment schedule described above (see footnote "o"). Brain metastases identified at baseline that have been treated with radiotherapy or surgery will not be considered measurable or evaluable unless there is suspected disease progression in the brain (i.e., the participant becomes symptomatic). Thus, subsequent head scans are not required unless clinically indicated. The same radiographic procedures used to assess disease sites at screening should be used for subsequent tumor assessments (e.g., the same contrast protocol for CT scans).
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 13	Repeat 1 time	Cycle length: 21 days	C13 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T3	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T4, FREE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 14	Repeat 1 time	Cycle length: 21 days	C14 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Baseline
  	ONC NURSING COMMUNICATION 104	Interval: --	Occurrences: --	Comments:	Participants will undergo tumor assessments at baseline, every 6 weeks (± 1 week) for the first 54 weeks following treatment initiation, and every 9 weeks (± 1 weeks) thereafter, regardless of dose delays, except in the case of participants who continue treatment after radiographic disease progression; such participants will undergo tumor assessments every 6 weeks (? 1 week) until loss of clinical benefit as determined by the investigator. Thus, tumor assessments are to continue according to schedule in participants who discontinue treatment for reasons other than loss of clinical benefit, even if they start new non-protocol-specified anti-cancer therapy.
All measurable and/or evaluable lesions identified at baseline should be re-assessed at subsequent tumor evaluations according to the tumor assessment schedule described above (see footnote "o"). Brain metastases identified at baseline that have been treated with radiotherapy or surgery will not be considered measurable or evaluable unless there is suspected disease progression in the brain (i.e., the participant becomes symptomatic). Thus, subsequent head scans are not required unless clinically indicated. The same radiographic procedures used to assess disease sites at screening should be used for subsequent tumor assessments (e.g., the same contrast protocol for CT scans).
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 15	Repeat 1 time	Cycle length: 21 days	C15D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 16	Repeat 1 time	Cycle length: 21 days	C16 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	Not applicable for a site that has not been granted approval for RBR sampling. Performed only for participants at participating sites who have provided written informed consent to participate
		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Baseline
  	ONC NURSING COMMUNICATION 104	Interval: --	Occurrences: --	Comments:	Participants will undergo tumor assessments at baseline, every 6 weeks (± 1 week) for the first 54 weeks following treatment initiation, and every 9 weeks (± 1 weeks) thereafter, regardless of dose delays, except in the case of participants who continue treatment after radiographic disease progression; such participants will undergo tumor assessments every 6 weeks (? 1 week) until loss of clinical benefit as determined by the investigator. Thus, tumor assessments are to continue according to schedule in participants who discontinue treatment for reasons other than loss of clinical benefit, even if they start new non-protocol-specified anti-cancer therapy.
All measurable and/or evaluable lesions identified at baseline should be re-assessed at subsequent tumor evaluations according to the tumor assessment schedule described above (see footnote "o"). Brain metastases identified at baseline that have been treated with radiotherapy or surgery will not be considered measurable or evaluable unless there is suspected disease progression in the brain (i.e., the participant becomes symptomatic). Thus, subsequent head scans are not required unless clinically indicated. The same radiographic procedures used to assess disease sites at screening should be used for subsequent tumor assessments (e.g., the same contrast protocol for CT scans).
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 17	Repeat 1 time	Cycle length: 21 days	C17 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T3	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T4, FREE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 18	Repeat 1 time	Cycle length: 21 days	C18 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Baseline
  	ONC NURSING COMMUNICATION 104	Interval: --	Occurrences: --	Comments:	Participants will undergo tumor assessments at baseline, every 6 weeks (± 1 week) for the first 54 weeks following treatment initiation, and every 9 weeks (± 1 weeks) thereafter, regardless of dose delays, except in the case of participants who continue treatment after radiographic disease progression; such participants will undergo tumor assessments every 6 weeks (? 1 week) until loss of clinical benefit as determined by the investigator. Thus, tumor assessments are to continue according to schedule in participants who discontinue treatment for reasons other than loss of clinical benefit, even if they start new non-protocol-specified anti-cancer therapy.
All measurable and/or evaluable lesions identified at baseline should be re-assessed at subsequent tumor evaluations according to the tumor assessment schedule described above (see footnote "o"). Brain metastases identified at baseline that have been treated with radiotherapy or surgery will not be considered measurable or evaluable unless there is suspected disease progression in the brain (i.e., the participant becomes symptomatic). Thus, subsequent head scans are not required unless clinically indicated. The same radiographic procedures used to assess disease sites at screening should be used for subsequent tumor assessments (e.g., the same contrast protocol for CT scans).
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 19	Repeat 1 time	Cycle length: 21 days	C19 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 20	Repeat 1 time	Cycle length: 21 days	C20 D1	Perform every 21 days x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Baseline
  	ONC NURSING COMMUNICATION 104	Interval: --	Occurrences: --	Comments:	Participants will undergo tumor assessments at baseline, every 6 weeks (± 1 week) for the first 54 weeks following treatment initiation, and every 9 weeks (± 1 weeks) thereafter, regardless of dose delays, except in the case of participants who continue treatment after radiographic disease progression; such participants will undergo tumor assessments every 6 weeks (? 1 week) until loss of clinical benefit as determined by the investigator. Thus, tumor assessments are to continue according to schedule in participants who discontinue treatment for reasons other than loss of clinical benefit, even if they start new non-protocol-specified anti-cancer therapy.
All measurable and/or evaluable lesions identified at baseline should be re-assessed at subsequent tumor evaluations according to the tumor assessment schedule described above (see footnote "o"). Brain metastases identified at baseline that have been treated with radiotherapy or surgery will not be considered measurable or evaluable unless there is suspected disease progression in the brain (i.e., the participant becomes symptomatic). Thus, subsequent head scans are not required unless clinically indicated. The same radiographic procedures used to assess disease sites at screening should be used for subsequent tumor assessments (e.g., the same contrast protocol for CT scans).
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
			Line Flush
  	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Nursing Orders
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Chemotherapy
  	INV-atezolizumab (CO44668/Pro00037748/Abdelrahim) 1,200 mg in sodium chloride 0.9% 250 mL IVPB	Dose: 1,200 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Atezolizumab 1200mg in 250mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 minutes for initial infusion, and over 30 minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 6 hours at room temperature (12 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ATEZOLIZUMAB 1,200 MG/20 ML (60 MG/ML) INTRAVENOUS SOL (ML41734PRO00026826/ZHANG)	Medications	1,200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	230 mL	Yes	Yes			  	INV-Bevacizumab (CO44668/Pro00037748/Abdelrahim) 15 mg/kg in sodium chloride 0.9% 100 mL IVPB	Dose: 15 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Bevacizumab 15mg/kg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 90 minutes (+15) for initial infusion, and over 60 (+10)minutes for second infusion if tolerated, then subsequent infusions over 30 (+10) minutes if tolerated per protocol instructions. Stability of prepared dose: infuse immediately or store refrigerated for up to 8 hours. 
Caution: New Drug - Limited by federal (USA) Law to investigational use.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-BEVACIZUMAB 25 MG/ML IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	15 mg/kg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes			  	INV-Tiragolumab/placebo (CO44668/Pro00037748/Abdelrahim) 600 mg in sodium chloride 0.9% 100 mL (6 mg/mL) IVPB	Dose: 600 mg	Route: intravenous	once over 60 Minutes for 1 dose	Start: S			Instructions:	Prepared IV bag contains Tiragolumab or placebo 600mg in 100mL 0.9% NaCl. Administer intravenously using a 0.2 micron inline filter over 60 (+/-15) minutes for initial infusion, and over 30 (+/-10) minutes of subsequent infusions if tolerated per protocol instructions. Stability of prepared dose: 4 hours at room temperature (24 hours refrigerated). 
Caution: New Drug - Limited by federal (USA) Law to investigational use. 

The interval between subsequent infusions will be at least 30 minutes if the previous bevacizumab infusion was given without premedication and tolerated without an IRR or at least 60 minutes if the participant experienced an IRR with the previous bevacizumab infusion.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-TIRAGOLUMAB/PLACEBO 600MG IV SOLN (CO44668/PRO00037748/ABDELRAHIM)	Medications	600 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	90 mL	Yes	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only – itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 – MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms – shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Fexofenadine 180 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
DV - Discontinuation Visit	Repeat 1 time	Cycle length: 1 day	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Participants who discontinue study treatment will return to the clinic for a treatment Discontinuation Visit 30 (+7) days after their final dose of study treatment. The visit at which response assessment shows progressive disease may be used as the treatment discontinuation visit.
			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol CO4468 for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines. Protocol Access Hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Refer to Appendix 4 for guidelines for management of Infusion Related Reactions (IRRs).  Protocol Access hyperlink: CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.1 and Table 7 for administration of first and subsequent infusion of ATEZOLIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Nursing Communication: Day 1 of each cycle, Bevacizumab will be administered at least 5 minutes after completion of the atezolizumab infusion. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.2 and Table 8 for administration of first and subsequent infusion of BEVACIZUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Section 6.5 dose modifications are not permitted; Refer to Section 6.1.3 and Table 9 for administration of first and subsequent infusion of TIRAGOLUMAB treatment. Protocol Access Hyperlink:  CO4468_Abdelrahim
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: Once	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of one pulse and three blood pressure measurements (three consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the three blood pressure readings will be recorded on the eCRF.
			Nursing Orders
  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --	Comments:	The dose of bevacizumab will be based on the participant's weight measured = 14 days prior to baseline (i.e., the initiation of study treatment) and will remain the same throughout the study unless there is a weight change of GREATER THAN OR EQUAL TO 10% from baseline. If re-baseline is needed, the latest baseline weight should always be used to calculate percent change in weight for all subsequent doses.
			Nursing Orders
  	ONC NURSING COMMUNICATION 62	Interval: --	Occurrences: --	Comments:	Limited physical examination
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --	Comments:	WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other cells)
		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --	Comments:	bicarbonate or total carbon dioxide (if considered standard
of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total bilirubin, ALP, ALT, AST, urate, and lactate
dehydrogenase
		☑	URIC ACID LEVEL	Interval: --	Occurrences: --	Comments:	Urate
		☑	LDH	Interval: --	Occurrences: --		☑	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		☑	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		☑	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		☑	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	Baseline urinalysis to be performed only if screening urinalysis is not performed within 7 days prior to initiation of study treatment. Participants with = 2+ protein on dipstick urinalysis must undergo a 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) and demonstrate < 1.0 g of protein in 24 hours. Urinalysis may be performed up to 72 hours prior to Day 1 of each cycle, as results must be available prior to treatment administration. 24-hour urine collection (or protein: creatinine ratio as an alternative per local practice) should be done prior to bevacizumab administration according to the guidelines in Table A4-1
			Labs
  	ALPHA FETOPROTEIN	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T3	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
		  	T4, FREE	Interval: --	Occurrences: --	Comments:	TSH, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycle 1 and every four cycles thereafter (i.e., Cycles 5, 9, 13, etc.).
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --		  	HEPATITIS B VIRUS (HBV), QUANTITATIVE, DNA (ABBOTT REALTIME)	Interval: --	Occurrences: --	Comments:	Participants without a prior positive HIV test result will undergo an HIV test, unless not permitted per local regulations. Participants will be tested for HbsAg, total HbcAb, and HCV antibody. If a participant has a positive HbsAg test and/or a positive total HbcAb test at screening, quantitative HbsAg and an HBV DNA test should be performed at screening. If local quantitative HbsAg test is not available, a qualitative HbsAg followed by quantitative HBV DNA can be performed as an alternative. Study treatment and procedures may proceed while HBV DNA is being processed, but results should be reviewed by the investigator as soon as they are available. If HBV DNA increases to greater than or equal to  500 IU/mL, consultation with a hepatologist or gastroenterologist with specialty in HBV is recommended. The Medical Monitor is available to advise as needed. If a participant has a positive HCV antibody test, an HCV RNA test must also be performed to determine if the participant has an HCV 
infection. Participants will also be tested for the following: (1) EBV VCA IgM, (2) EBV VCA IgG or EBNA IgG, and (3) EBV PCR (only if clinically indicated).
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA 

Participants without a prior positive HIV test result will undergo an HIV test, unless not permitted per local regulations. Participants will be tested for HbsAg, total HbcAb, and HCV antibody. If a participant has a positive HbsAg test and/or a positive total HbcAb test at screening, quantitative HbsAg and an HBV DNA test should be performed at screening. If local quantitative HbsAg test is not available, a qualitative HbsAg followed by quantitative HBV DNA can be performed as an alternative. Study treatment and procedures may proceed while HBV DNA is being processed, but results should be reviewed by the investigator as soon as they are available. If HBV DNA increases to greater than or equal to 500 IU/mL, consultation with a hepatologist or gastroenterologist with specialty in HBV is recommended. The Medical Monitor is available to advise as needed. If a participant has a positive HCV antibody test, an HCV RNA test must also be performed to determine if the participant has an HCV 
infection. Participants will also be tested for the following: (1) EBV VCA IgM, (2) EBV VCA IgG or EBNA IgG, and (3) EBV PCR (only if clinically indicated).
			Labs
  	SOLUBLE LIVER ANTIGEN (SLA) AUTOANTIBODY	Interval: --	Occurrences: --	Comments:	Serum autoantibody analysis 

Autoantibody analysis should be repeated for participants who develop signs or symptoms suggestive of autoimmune disease (e.g., lupus erythematosus) as clinically indicated.
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	Not applicable for a site that has not been granted approval for RBR sampling. Performed only for participants at participating sites who have provided written informed consent to participate
		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Procedures
  	BIOPSY	Interval: --	Occurrences: --	Comments:	Bevacizumab must be administered greater than or equal to 3 days after any biopsy, but only after adequate wound healing has been demonstrated. The biopsy should not be performed in an anatomic location at risk for excessive bleeding, as determined by the investigator.

Participants who consent to optional biopsies may undergo tumor biopsy sample collection at any time after treatment initiation, if deemed clinically feasible and at the investigator's discretion.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medication.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first. Adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, all deaths, regardless of cause, should be reported. In addition, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior exposure to study treatment. The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or trial-related procedures until a final outcome can be reported.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC IL46 

See Table 3 for at Home timepoints
					
LTFU 	Repeat 1 time	Cycle length: 84 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Survival follow-up and anti-cancer treatment 

After treatment discontinuation, information on survival follow-up and new anti-cancer therapy (including targeted therapy and immunotherapy) will be collected via telephone calls, participant medical records, and/or clinic visits approximately every 3 months until death (unless the participant withdraws consent, or the Sponsor terminates the study). If a participant requests to be withdrawn from follow-up, this request must be documented in the source documents and signed by the investigator. If the participant withdraws from the study, the study staff may use a public information source (e.g., county records) to obtain information about survival status only.
			Nursing Orders
  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	EORTC QLQ-C30,  EORTC QLQ-HCC18,   EQ-5D-5L,  PRO-CTCAE 

See Table 3 for at Home timepoints