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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02420821




Registration number
NCT02420821
Ethics application status
Date submitted
15/04/2015
Date registered
20/04/2015
Date last updated
29/07/2021

Titles & IDs
Public title
A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC)
Scientific title
A Phase III, Open-Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
Secondary ID [1] 0 0
2014-004684-20
Secondary ID [2] 0 0
WO29637
Universal Trial Number (UTN)
Trial acronym
IMmotion151
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Sunitinib

Experimental: Atezolizumab + Bevacizumab - Participants 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.

Active Comparator: Sunitinib - Participants 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.


Treatment: Drugs: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Days 1 and 22 of each 42-day cycle.

Treatment: Drugs: Bevacizumab
Bevacizumab will be administered at a dose of 15 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 22 of each 42-day cycle.

Treatment: Drugs: Sunitinib
Sunitinib will be administered at a dose of 50 mg once daily, orally via capsule, on Day 1 through Day 28 of each 42-day cycle.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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 Population - 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.
Timepoint [1] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Primary outcome [2] 0 0
Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected Population - 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.
Timepoint [2] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Primary outcome [3] 0 0
Percentage of Participants Who Died of Any Cause in ITT Population - Percentage of participants who died of any cause was reported.
Timepoint [3] 0 0
Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Primary outcome [4] 0 0
Overall Survival (OS) in ITT Population - 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.
Timepoint [4] 0 0
Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Secondary outcome [1] 0 0
Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population - Percentage of participants who died of any cause was reported.
Timepoint [1] 0 0
Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Secondary outcome [2] 0 0
OS in PD-L1-Selected Population - 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.
Timepoint [2] 0 0
Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Secondary outcome [3] 0 0
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 Population - 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.
Timepoint [3] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [4] 0 0
PFS as Determined by an IRC According to RECIST v1.1 in ITT Population - 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.
Timepoint [4] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [5] 0 0
Percentage of Participants With PD as Determined by an IRC According to RECIST v1.1 or Death From Any Cause in PD-L1-Selected Population - 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.
Timepoint [5] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [6] 0 0
PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected Population - 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.
Timepoint [6] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [7] 0 0
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 Population - 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.
Timepoint [7] 0 0
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [8] 0 0
Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable Population - 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.
Timepoint [8] 0 0
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [9] 0 0
Percentage of Participants With an Objective Response of CR or PR as Determined by an IRC According to RECIST v1.1 in ORR-Evaluable Population - 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.
Timepoint [9] 0 0
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [10] 0 0
DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable Population - 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.
Timepoint [10] 0 0
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [11] 0 0
Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT Population - 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.
Timepoint [11] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [12] 0 0
PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT Population - 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.
Timepoint [12] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [13] 0 0
Percentage of Participants With an Objective Response of CR or PR as Determined by the Investigator According to Immune-Modified RECIST in ORR-Evaluable Population - 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.
Timepoint [13] 0 0
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [14] 0 0
DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable Population - 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.
Timepoint [14] 0 0
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [15] 0 0
Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT Population - 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.
Timepoint [15] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [16] 0 0
PFS as Determined by the Investigator According to RECIST v1.1 in ITT Population - 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.
Timepoint [16] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [17] 0 0
Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in Participants With Sarcomatoid Histology - 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.
Timepoint [17] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [18] 0 0
PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid Histology - 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.
Timepoint [18] 0 0
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Secondary outcome [19] 0 0
Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid Histology - Percentage of participants who died of any cause was reported.
Timepoint [19] 0 0
Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Secondary outcome [20] 0 0
OS in Participants With Sarcomatoid Histology - 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.
Timepoint [20] 0 0
Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Secondary outcome [21] 0 0
Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II Score - 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.
Timepoint [21] 0 0
Baseline (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
Secondary outcome [22] 0 0
Change From Baseline in Symptom Severity as Determined by MDASI Part I Score - 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.
Timepoint [22] 0 0
Baseline; End of Treatment (EoT) visit (up to approximately 27 months)
Secondary outcome [23] 0 0
Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale Score - 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.
Timepoint [23] 0 0
Baseline (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
Secondary outcome [24] 0 0
Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue Item - 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.
Timepoint [24] 0 0
Baseline (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
Secondary outcome [25] 0 0
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 Score - 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.
Timepoint [25] 0 0
Day 1 and 22 of every cycle (Baseline = Day 1 Cycle 1) up to Cycle 19; Cycle length = 42 days
Secondary outcome [26] 0 0
Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab - 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.
Timepoint [26] 0 0
Baseline (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)
Secondary outcome [27] 0 0
Number of Participants With ATAs Against Bevacizumab - 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.
Timepoint [27] 0 0
Baseline (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)
Secondary outcome [28] 0 0
Maximum Observed Serum Concentration (Cmax) for Atezolizumab - Cmax for atezolizumab was estimated from plasma concentration versus time data.
Timepoint [28] 0 0
30 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)
Secondary outcome [29] 0 0
Minimum Observed Serum Concentration (Cmin) for Atezolizumab - Cmin for atezolizumab was estimated from plasma concentration versus time data.
Timepoint [29] 0 0
Predose (Hour 0) on Day 22 of Cycle 1; predose (Hour 0) on Day 1 of Cycles 2; Cycle length = 42 days
Secondary outcome [30] 0 0
Cmax for Bevacizumab - Cmax for bevacizumab was estimated from plasma concentration versus time data.
Timepoint [30] 0 0
30 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)
Secondary outcome [31] 0 0
Cmin for Bevacizumab - Cmin for bevacizumab was estimated from plasma concentration versus time data.
Timepoint [31] 0 0
Pre-dose (Hour 0) on Day 1 of Cycle 3 (Cycle length = 42 days)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [3] 0 0
Calvary Mater Newcastle; Medical Oncology - Waratah
Recruitment hospital [4] 0 0
Icon Cancer Foundation - South Brisbane
Recruitment hospital [5] 0 0
Ashford Cancer Center Research - Kurralta Park
Recruitment hospital [6] 0 0
Austin Hospital; Medical Oncology - Heidelberg
Recruitment hospital [7] 0 0
St John of God Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2109 - Macquarie Park
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
WA6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Nevada
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oregon
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
Country [18] 0 0
United States of America
State/province [18] 0 0
Washington
Country [19] 0 0
Bosnia and Herzegovina
State/province [19] 0 0
Banja Luka
Country [20] 0 0
Brazil
State/province [20] 0 0
RS
Country [21] 0 0
Brazil
State/province [21] 0 0
SP
Country [22] 0 0
Canada
State/province [22] 0 0
Nova Scotia
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
Czechia
State/province [25] 0 0
Brno
Country [26] 0 0
Czechia
State/province [26] 0 0
Olomouc
Country [27] 0 0
Czechia
State/province [27] 0 0
Praha 2
Country [28] 0 0
Czechia
State/province [28] 0 0
Praha 4 - Krc
Country [29] 0 0
Denmark
State/province [29] 0 0
Aarhus N
Country [30] 0 0
Denmark
State/province [30] 0 0
Herlev
Country [31] 0 0
Denmark
State/province [31] 0 0
Odense C
Country [32] 0 0
France
State/province [32] 0 0
Angers
Country [33] 0 0
France
State/province [33] 0 0
Bordeaux
Country [34] 0 0
France
State/province [34] 0 0
Caen
Country [35] 0 0
France
State/province [35] 0 0
Lille
Country [36] 0 0
France
State/province [36] 0 0
Lyon
Country [37] 0 0
France
State/province [37] 0 0
Marseille
Country [38] 0 0
France
State/province [38] 0 0
Nancy
Country [39] 0 0
France
State/province [39] 0 0
Paris
Country [40] 0 0
France
State/province [40] 0 0
Saint Herblain
Country [41] 0 0
France
State/province [41] 0 0
Villejuif
Country [42] 0 0
Germany
State/province [42] 0 0
Dresden
Country [43] 0 0
Germany
State/province [43] 0 0
Essen
Country [44] 0 0
Germany
State/province [44] 0 0
Heidelberg
Country [45] 0 0
Germany
State/province [45] 0 0
München
Country [46] 0 0
Germany
State/province [46] 0 0
Tübingen
Country [47] 0 0
Italy
State/province [47] 0 0
Campania
Country [48] 0 0
Italy
State/province [48] 0 0
Emilia-Romagna
Country [49] 0 0
Italy
State/province [49] 0 0
Lazio
Country [50] 0 0
Italy
State/province [50] 0 0
Lombardia
Country [51] 0 0
Italy
State/province [51] 0 0
Toscana
Country [52] 0 0
Japan
State/province [52] 0 0
Aichi
Country [53] 0 0
Japan
State/province [53] 0 0
Chiba
Country [54] 0 0
Japan
State/province [54] 0 0
Fukuoka
Country [55] 0 0
Japan
State/province [55] 0 0
Gunma
Country [56] 0 0
Japan
State/province [56] 0 0
Hokkaido
Country [57] 0 0
Japan
State/province [57] 0 0
Ibaraki
Country [58] 0 0
Japan
State/province [58] 0 0
Iwate
Country [59] 0 0
Japan
State/province [59] 0 0
Kanagawa
Country [60] 0 0
Japan
State/province [60] 0 0
Kumamoto
Country [61] 0 0
Japan
State/province [61] 0 0
Niigata
Country [62] 0 0
Japan
State/province [62] 0 0
Okayama
Country [63] 0 0
Japan
State/province [63] 0 0
Osaka
Country [64] 0 0
Japan
State/province [64] 0 0
Tokushima
Country [65] 0 0
Japan
State/province [65] 0 0
Tokyo
Country [66] 0 0
Korea, Republic of
State/province [66] 0 0
Daejeon
Country [67] 0 0
Korea, Republic of
State/province [67] 0 0
Goyang-si
Country [68] 0 0
Korea, Republic of
State/province [68] 0 0
Seongnam-si
Country [69] 0 0
Korea, Republic of
State/province [69] 0 0
Seoul
Country [70] 0 0
Mexico
State/province [70] 0 0
Queretaro
Country [71] 0 0
Mexico
State/province [71] 0 0
Toluca
Country [72] 0 0
Poland
State/province [72] 0 0
Lublin
Country [73] 0 0
Poland
State/province [73] 0 0
Poznan
Country [74] 0 0
Poland
State/province [74] 0 0
Warsaw
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Altaj
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Moskovskaja Oblast
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Niznij Novgorod
Country [78] 0 0
Russian Federation
State/province [78] 0 0
Moscow
Country [79] 0 0
Singapore
State/province [79] 0 0
Singapore
Country [80] 0 0
Spain
State/province [80] 0 0
Barcelona
Country [81] 0 0
Spain
State/province [81] 0 0
Cordoba
Country [82] 0 0
Spain
State/province [82] 0 0
Madrid
Country [83] 0 0
Spain
State/province [83] 0 0
Sevilla
Country [84] 0 0
Taiwan
State/province [84] 0 0
Taichung
Country [85] 0 0
Taiwan
State/province [85] 0 0
Taipei
Country [86] 0 0
Taiwan
State/province [86] 0 0
Taoyuan
Country [87] 0 0
Thailand
State/province [87] 0 0
Bangkok
Country [88] 0 0
Thailand
State/province [88] 0 0
Chiangmai
Country [89] 0 0
Thailand
State/province [89] 0 0
Songkhla
Country [90] 0 0
Turkey
State/province [90] 0 0
Ankara
Country [91] 0 0
Turkey
State/province [91] 0 0
Edirne
Country [92] 0 0
Turkey
State/province [92] 0 0
Istanbul
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Bebington
Country [94] 0 0
United Kingdom
State/province [94] 0 0
Birmingham
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Blackburn
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Cambridge
Country [97] 0 0
United Kingdom
State/province [97] 0 0
London
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Manchester
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Oxford
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Southampton
Country [101] 0 0
United Kingdom
State/province [101] 0 0
Sutton
Country [102] 0 0
United Kingdom
State/province [102] 0 0
Swansea

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02420821
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications