MedPath

A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC)

Registration Number
NCT02420821
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This multi-center, randomized, open-label study will evaluate the efficacy and safety of atezolizumab plus bevacizumab versus sunitinib in participants with inoperable, locally advanced, or metastatic RCC who have not received prior systemic active or experimental therapy, either in the adjuvant or metastatic setting.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
915
Inclusion Criteria
  • Definitive diagnosis of unresectable locally advanced or metastatic RCC with clear-cell histology and/or a component of sarcomatoid carcinoma, with no prior treatment in the metastatic setting
  • Evaluable Memorial Sloan Kettering Cancer Center risk score
  • Measurable disease, as defined by RECIST v1.1
  • Karnofsky performance status greater than or equal to 70%
  • Adequate hematologic and end-organ function prior to randomization
Exclusion Criteria

Disease-Specific Exclusions:

  • Radiotherapy for RCC within 14 days prior to treatment
  • Active central nervous system disease
  • Uncontrolled pleural effusion, pericardial effusion, or ascites
  • Uncontrolled hypercalcemia
  • Any other malignancies within 5 years except for low-risk prostate cancer or those with negligible risk of metastasis or death

General Medical Exclusions:

  • Life expectancy less than 12 weeks
  • Participation in another experimental drug study within 4 weeks prior to treatment
  • Pregnant or lactating women
  • Known hypersensitivity to any component of atezolizumab or other study medication
  • History of autoimmune disease except controlled, treated hypothyroidism or type I diabetes mellitus
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis
  • Positive human immunodeficiency virus test
  • Active or chronic hepatitis B or C
  • Severe infections within 4 weeks prior to treatment
  • Exposure to oral or IV antibiotics within 2 weeks prior to treatment
  • Live attenuated vaccines within 4 weeks prior to treatment (for influenza vaccination participants must agree not to receive live, attenuated influenza vaccine within 4 weeks prior to treatment, during treatment or within 5 months following the last dose)
  • Significant cardiovascular disease
  • Prior allogeneic stem cell or solid organ transplantation

Exclusion Criteria Related to Medications:

  • Prior treatment with cluster of differentiation 137 agonists, anti-cytotoxic T-lymphocyte associated protein-4, anti-programmed death (PD)-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
  • Treatment with immunostimulatory agents for non-malignant conditions within 6 weeks or immunosuppressive agents within 2 weeks prior to treatment

Bevacizumab- and Sunitinib-Specific Exclusions:

  • History of hypertensive crisis or hypertensive encephalopathy
  • Baseline electrocardiogram showing corrected QT interval greater than 460 milliseconds

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Atezolizumab + BevacizumabAtezolizumab (MPDL3280A), an engineered anti-PD-L1 antibodyParticipants will receive both atezolizumab and bevacizumab until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.
SunitinibSunitinibParticipants will receive sunitinib until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.
Atezolizumab + BevacizumabBevacizumabParticipants will receive both atezolizumab and bevacizumab until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Disease Progression as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death From Any Cause in Programmed Death-Ligand 1 (PD-L1)-Selected PopulationBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Tumor response was assessed by the investigator according to RECIST v1.1. Disease Progression (PD) was defined as greater than or equal to (\>/=) 20 percent (%) relative increase in the sum of diameters (SoD) of all target lesions (TLs), taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 millimeters (mm); \>/=1 new lesion(s); and/or unequivocal progression of existing non-TLs.

Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected PopulationBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. PD: \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed \>/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% confidence interval (CI) was assessed using the method of Brookmeyer and Crowley.

Percentage of Participants Who Died of Any Cause in ITT PopulationBaseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)

Percentage of participants who died of any cause was reported.

Overall Survival (OS) in ITT PopulationBaseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)

OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Who Died of Any Cause in PD-L1-Selected PopulationBaseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)

Percentage of participants who died of any cause was reported.

OS in PD-L1-Selected PopulationBaseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)

OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

Percentage of Participants With PD as Determined by an Independent Review Committee (IRC) According to RECIST v1.1 or Death From Any Cause in ITT PopulationBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs.

PFS as Determined by an IRC According to RECIST v1.1 in ITT PopulationBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

Percentage of Participants With PD as Determined by an IRC According to RECIST v1.1 or Death From Any Cause in PD-L1-Selected PopulationBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs.

PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected PopulationBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator According to RECIST v1.1 in Objective Response Rate (ORR)-Evaluable PopulationBaseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to less than (\<) 10 mm. PR was defined as \>/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of \>/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.

Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable PopulationBaseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to \<10 mm. PR: \>/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of \>/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.

Percentage of Participants With an Objective Response of CR or PR as Determined by an IRC According to RECIST v1.1 in ORR-Evaluable PopulationBaseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Tumor response was assessed by an IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to \<10 mm. PR was defined as \>/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of \>/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.

DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable PopulationBaseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

DOR was defined as the time from the first occurrence of CR/PR to PD as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to \<10 mm. PR: \>/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of \>/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.

Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue ItemBaseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days

The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI worst fatigue item assessed the severity of fatigue at its worst in the last 24 hours. The item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Change from baseline in the score at each time point is reported, where a negative value indicates improvement.

Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT PopulationBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Tumor response was assessed by the investigator according to immune-modified RECIST. PD was defined as \>/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm.

PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT PopulationBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

PFS was defined as the time from randomization to PD, as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. PD: \>/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

Percentage of Participants With an Objective Response of CR or PR as Determined by the Investigator According to Immune-Modified RECIST in ORR-Evaluable PopulationBaseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Tumor response was assessed by the investigator according to immune-modified RECIST. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs or reduction in short axis of any pathological lymph nodes to \<10 mm. PR was defined as \>/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.

DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable PopulationBaseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs or reduction in short axis of any pathological lymph nodes to \<10 mm. PR: \>/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. PD: \>/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.

Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT PopulationBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs.

PFS as Determined by the Investigator According to RECIST v1.1 in ITT PopulationBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed \>/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in Participants With Sarcomatoid HistologyBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs.

PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid HistologyBaseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid HistologyBaseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)

Percentage of participants with sarcomatoid histology who died of any cause was reported.

OS in Participants With Sarcomatoid HistologyBaseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)

OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II ScoreBaseline (Day 1 Cycle 1); Day 22 Cycle 1; Day 1 and 22 of every cycle from Cycle 2 up to Cycle 19; Cycle length = 42 days

The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part II, participants were asked to rate how much the symptoms have interfered with 6 areas of function (general activity, walking, work, mood, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely) and total Part II score was calculated as an average of 6-item scores. Repeated measures model-estimated least-squares (LS) mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement. Here, 'Number Analyzed' = number of participants evaluable at specified time point.

Change From Baseline in Symptom Severity as Determined by MDASI Part I ScoreBaseline; End of Treatment (EoT) visit (up to approximately 27 months)

The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part I, participants were asked to rate how severe the symptoms (pain, fatigue, nausea, disturbed sleep, feeling of being distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, feeling sad, vomiting, numbness or tingling, rash/skin changes, headache, mouth/throat sores, and diarrhea) were when "at their worst" in the last 24 hours. Each item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Mixed-effects model-estimated LS mean score for change from baseline at the end-of treatment is reported for each item, where a negative value indicates improvement.

Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale ScoreBaseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days

The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI interference subscale (6 items) assessed the impact of fatigue on global domains (general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely). Change from baseline in the mean score of all 6 items at each timepoint is reported, where a negative value indicates improvement.

Change From Baseline in Treatment Side Effects Burden as Determined by Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-19) General Population 5 (GP5) Item ScoreDay 1 and 22 of every cycle (Baseline = Day 1 Cycle 1) up to Cycle 19; Cycle length = 42 days

The FKSI-19 is a 19-item tool designed to assess the most important symptoms and concerns related to treatment effectiveness in advanced kidney cancer. The FKSI-19 GP5 item (bothered by the side effect of treatment) assessed side effects burden in the past 7 days on a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Repeated measures model-estimated LS mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement.

Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against AtezolizumabBaseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycles 2, 4, and 8, and every eight cycles thereafter up to EoT [up to approximately 27 months] and 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days)

The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against atezolizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result. Here, 'Overall Number of Participants Analyzed' = number of participants with a non-missing baseline ATA sample; 'Number Analyzed' = number of participants with a non-missing ATA sample at indicated timepoint.

Number of Participants With ATAs Against BevacizumabBaseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycle 3, at EoT [up to approximately 27 months] and at 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days)

The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against bevacizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.

Maximum Observed Serum Concentration (Cmax) for Atezolizumab30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days)

Cmax for atezolizumab was estimated from plasma concentration versus time data.

Minimum Observed Serum Concentration (Cmin) for AtezolizumabPredose (Hour 0) on Day 22 of Cycle 1; predose (Hour 0) on Day 1 of Cycles 2; Cycle length = 42 days

Cmin for atezolizumab was estimated from plasma concentration versus time data.

Cmax for Bevacizumab30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days)

Cmax for bevacizumab was estimated from plasma concentration versus time data.

Cmin for BevacizumabPre-dose (Hour 0) on Day 1 of Cycle 3 (Cycle length = 42 days)

Cmin for bevacizumab was estimated from plasma concentration versus time data.

Trial Locations

Locations (154)

Lynn Cancer Institute/Boca Raton Regional Hospital

🇺🇸

Boca Raton, Florida, United States

Florida Cancer Specialists - Port Charlotte

🇺🇸

Port Charlotte, Florida, United States

Texas Oncology-Baylor Sammons Cancer Center

🇺🇸

Dallas, Texas, United States

Piedmont Cancer Institute, PC

🇺🇸

Atlanta, Georgia, United States

Lifehouse

🇦🇺

Camperdown, New South Wales, Australia

St John of God Hospital

🇦🇺

Murdoch, Western Australia, Australia

Sunnybrook Odette Cancer Centre

🇨🇦

Toronto, Ontario, Canada

Cleveland Clinic Foundation; Taussig Cancer Center

🇺🇸

Cleveland, Ohio, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Dana Farber Cancer Inst.

🇺🇸

Boston, Massachusetts, United States

Comprehensive Cancer Centers of Nevada - Eastern Avenue

🇺🇸

Las Vegas, Nevada, United States

Oncology Hematology Care Inc

🇺🇸

Cincinnati, Ohio, United States

Seattle Cancer Care Alliance

🇺🇸

Seattle, Washington, United States

University of Arizona Cancer Center

🇺🇸

Tucson, Arizona, United States

Queen Elizabeth II Health Sciences Centre; Oncology

🇨🇦

Halifax, Nova Scotia, Canada

Instituto do Cancer do Estado de Sao Paulo - ICESP

🇧🇷

Sao Paulo, SP, Brazil

Royal Victoria Hospital

🇨🇦

Barrie, Ontario, Canada

ICO - Site René Gauducheau

🇫🇷

Saint Herblain, France

Institut Gustave Roussy; Departement Oncologie Medicale

🇫🇷

Villejuif, France

A.O. Universitaria Policlinico Di Modena; Oncologia

🇮🇹

Modena, Emilia-Romagna, Italy

Hamilton Health Sciences - Juravinski Cancer Centre

🇨🇦

Hamilton, Ontario, Canada

The Ottawa Hospital Cancer Centre; Oncology

🇨🇦

Ottawa, Ontario, Canada

ICO Paul Papin; Oncologie Medicale.

🇫🇷

Angers, France

Centre Francois Baclesse; Urologie Gynecologie

🇫🇷

Caen, France

Osaka International Cancer Institute; Urology

🇯🇵

Osaka, Japan

National Cancer Center

🇰🇷

Goyang-si, Korea, Republic of

Niigata University Medical & Dental Hospital

🇯🇵

Niigata, Japan

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

🇪🇸

Sevilla, Spain

Hospital Ramon y Cajal; Servicio de Oncologia

🇪🇸

Madrid, Spain

Taichung Veterans General Hospital; Division of Urology

🇨🇳

Taichung, Taiwan

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

🇪🇸

Sabadell, Barcelona, Spain

Royal Marsden Hospital; Dept of Medical Oncology

🇬🇧

Sutton, United Kingdom

ALTAI REGIONAL ONCOLOGICAL CENTER; "Nadezhda" Clinic

🇷🇺

Barnaul, Altaj, Russian Federation

Maharaj Nakorn Chiangmai Hospital; Department of Surgery/ Urology unit

🇹🇭

Chiangmai, Thailand

P.A. Herzen Oncological Inst. ; Oncology

🇷🇺

Moscow, Russian Federation

Centro Oncologico Estatal ISSEMYM

🇲🇽

Toluca, Mexico

Hospital Universitario Reina Sofia; Servicio de Oncologia

🇪🇸

Córdoba, Cordoba, Spain

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Szpital Kliniczny; Przemienienia Panskiego;Uniwersytetu Medyczny im.; Karola Marcinkowskiego w Pozna

🇵🇱

Poznan, Poland

Royal Free Hospital; Dept of Oncology

🇬🇧

London, United Kingdom

University of California

🇺🇸

San Francisco, California, United States

Sarah Cannon Cancer Center and Research Institute

🇺🇸

Nashville, Tennessee, United States

London Regional Cancer Centre

🇨🇦

London, Ontario, Canada

Princess Margaret Cancer Center

🇨🇦

Toronto, Ontario, Canada

Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie

🇩🇪

Dresden, Germany

Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung

🇩🇪

Essen, Germany

Lakeridge Health Oshawa; Oncology

🇨🇦

Oshawa, Ontario, Canada

University of California at Irvine Medical Center; Department of Oncology

🇺🇸

Orange, California, United States

Georgetown U; Lombardi Comp Can

🇺🇸

Washington, District of Columbia, United States

Rocky Mountain Cancer Center; Medical Oncology

🇺🇸

Boulder, Colorado, United States

Florida Cancer Specialist, North Region

🇺🇸

Saint Petersburg, Florida, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

New York Oncology Hematology,P.C.-Albany

🇺🇸

Albany, New York, United States

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Northwest Cancer Specialists, P.C.

🇺🇸

Tigard, Oregon, United States

Memorial Sloan-Kettering Cancer Center

🇺🇸

New York, New York, United States

SCRI Tennessee Oncology Chattanooga

🇺🇸

Chattanooga, Tennessee, United States

Oncology and Hematology Associates of SW Virginia-Raonoke

🇺🇸

Roanoke, Virginia, United States

Vanderbilt Univ Medical Ctr

🇺🇸

Nashville, Tennessee, United States

Calvary Mater Newcastle; Medical Oncology

🇦🇺

Waratah, New South Wales, Australia

Macquarie University Hospital

🇦🇺

Macquarie Park, New South Wales, Australia

Ashford Cancer Center Research

🇦🇺

Kurralta Park, South Australia, Australia

Icon Cancer Foundation

🇦🇺

South Brisbane, Queensland, Australia

Austin Hospital; Medical Oncology

🇦🇺

Heidelberg, Victoria, Australia

University Clinical Centre of the Republic of Srpska

🇧🇦

Banja Luka, Bosnia and Herzegovina

Santa Casa de Misericordia de Porto Alegre

🇧🇷

Porto Alegre, RS, Brazil

Hospital de Caridade de Ijui; Oncologia

🇧🇷

Ijui, RS, Brazil

Hospital Sao Lucas - PUCRS

🇧🇷

Porto Alegre, RS, Brazil

CHU de Quebec Hotel-Dieu de Quebec

🇨🇦

Quebec City, Quebec, Canada

Jewish General Hospital

🇨🇦

Montreal, Quebec, Canada

Thomayerova nemocnice

🇨🇿

Praha 4 - Krc, Czechia

Masarykuv onkologicky ustav

🇨🇿

Brno, Czechia

Fakultni nemocnice Olomouc; Onkologicka klinika

🇨🇿

Olomouc, Czechia

Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika

🇨🇿

Praha 2, Czechia

Aarhus Universitetshospital; Kræftafdelingen

🇩🇰

Aarhus N, Denmark

Herlev Hospital; Afdeling for Kræftbehandling

🇩🇰

Herlev, Denmark

Hopital Saint Andre; Oncologie 2

🇫🇷

Bordeaux, France

Centre Oscar Lambret

🇫🇷

Lille, France

Odense Universitetshospital, Onkologisk Afdeling R

🇩🇰

Odense C, Denmark

Centre D'Oncologie de Gentilly; Oncology

🇫🇷

Nancy, France

APHP - Hospital Saint Louis

🇫🇷

Paris, France

Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale

🇫🇷

Paris, France

Centre Léon Bérard

🇫🇷

Lyon, France

Institut Paoli Calmettes; Oncologie Medicale

🇫🇷

Marseille, France

Nationales Centrum für Tumorerkrankungen Heidelberg (NCT); Thoraxklinik Heidelberg

🇩🇪

Heidelberg, Germany

Klinikum d.Universität München Campus Großhadern

🇩🇪

München, Germany

Universitätsklinikum Tübingen; Klinik für Urologie

🇩🇪

Tübingen, Germany

Irccs Ospedale San Raffaele;Oncologia Medica

🇮🇹

Milano, Lombardia, Italy

Az. Osp. Cardarelli; Divisione Di Oncologia

🇮🇹

Napoli, Campania, Italy

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

🇮🇹

Milano, Lombardia, Italy

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

🇮🇹

Meldola, Emilia-Romagna, Italy

Fondazione IRCCS Policlinico San Matteo, Oncologia

🇮🇹

Pavia, Lombardia, Italy

Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia

🇮🇹

Arezzo, Toscana, Italy

Nagoya University Hospital; Urology

🇯🇵

Aichi, Japan

Kyushu University Hospital

🇯🇵

Fukuoka, Japan

Chiba Cancer Center

🇯🇵

Chiba, Japan

Gunma University Hospital

🇯🇵

Gunma, Japan

Hokkaido University Hospital

🇯🇵

Hokkaido, Japan

University of Tsukuba Hospital; Urology

🇯🇵

Ibaraki, Japan

Iwate Medical University Hospital

🇯🇵

Iwate, Japan

Yokohama City University Hospital

🇯🇵

Kanagawa, Japan

Kitasato University Hospital

🇯🇵

Kanagawa, Japan

Kumamoto University Hospital

🇯🇵

Kumamoto, Japan

Osaka Metropolitan University Hospital

🇯🇵

Osaka, Japan

Okayama University Hospital

🇯🇵

Okayama, Japan

Kindai University Hospital

🇯🇵

Osaka, Japan

Osaka University Hospital

🇯🇵

Osaka, Japan

Keio University Hospital

🇯🇵

Tokyo, Japan

Tokyo Medical and Dental University Hospital

🇯🇵

Tokyo, Japan

Tokushima University Hospital

🇯🇵

Tokushima, Japan

The Cancer Institute Hospital, JFCR; Urology

🇯🇵

Tokyo, Japan

Nippon Medical School Hospital

🇯🇵

Tokyo, Japan

Toranomon Hospital

🇯🇵

Tokyo, Japan

Tokyo Women's Medical University

🇯🇵

Tokyo, Japan

Chungnam National University Hospital

🇰🇷

Daejeon, Korea, Republic of

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Seoul National University Bundang Hospital

🇰🇷

Seongnam-si, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

GBUZ Nizhegorodskay Region: Clinical Diagnostic Center

🇷🇺

Nizhni Novgorod, Niznij Novgorod, Russian Federation

MAGODENT Sp. z o.o.

🇵🇱

Warsaw, Poland

City Clinical Oncology Hospital

🇷🇺

Moscow, Russian Federation

Hospital Clínic i Provincial; Servicio de Oncología

🇪🇸

Barcelona, Spain

National Cancer Centre; Medical Oncology

🇸🇬

Singapore, Singapore

Hospital Univ Vall d'Hebron; Servicio de Oncologia

🇪🇸

Barcelona, Spain

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

🇪🇸

Madrid, Spain

Hospital Duran i Reynals; Oncologia

🇪🇸

Barcelona, Spain

Hospital Universitario 12 de Octubre; Servicio de Oncologia

🇪🇸

Madrid, Spain

National Taiwan Uni Hospital; Dept of Oncology

🇨🇳

Taipei, Taiwan

Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc

🇹🇭

Bangkok, Thailand

Songklanagarind Hospital; Department of Oncology

🇹🇭

Songkhla, Thailand

Hacettepe University Medical Faculty

🇹🇷

Ankara, Turkey

Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department

🇹🇷

Edirne, Turkey

Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology

🇹🇷

Istanbul, Turkey

Addenbrookes Nhs Trust; Oncology Clinical Trials Unit

🇬🇧

Cambridge, United Kingdom

Queen Elizabeth Hospital

🇬🇧

Birmingham, United Kingdom

Clatterbridge Cancer Centre

🇬🇧

Bebington, United Kingdom

Royal Blackburn Hospital

🇬🇧

Blackburn, United Kingdom

Barts Health NHS Trust - St Bartholomew's Hospital

🇬🇧

London, United Kingdom

Churchill Hospital; Oxford Cancer and Haematology Centre

🇬🇧

Oxford, United Kingdom

Christie Hospital Nhs Trust; Medical Oncology

🇬🇧

Manchester, United Kingdom

Singleton Hospital; Pharmacy Department

🇬🇧

Swansea, United Kingdom

Southampton General Hospital; Medical Oncology

🇬🇧

Southampton, United Kingdom

Norton Cancer Institute

🇺🇸

Louisville, Kentucky, United States

University of Colorado; Anschutz Cancer Pavilion

🇺🇸

Aurora, Colorado, United States

Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology

🇹🇭

Bangkok, Thailand

Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli

🇵🇱

Lublin, Poland

National University Hospital

🇸🇬

Singapore, Singapore

Chulalongkorn Hospital; Medical Oncology

🇹🇭

Bangkok, Thailand

Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica

🇮🇹

Roma, Lazio, Italy

Chang Gung Medical Foundation-Linkou, Urinary Oncology

🇨🇳

Taoyuan, Taiwan

Cancerología

🇲🇽

Queretaro, Mexico

Saint Elizabeth's Hospital

🇵🇱

Warsaw, Poland

The University of Chicago

🇺🇸

Chicago, Illinois, United States

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