A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC) (IMmotion151)

• ClinicalTrials.gov Identifier: NCT02420821
• Recruitment Status: Completed
• First Posted: April 20, 2015
• Results First Posted: October 3, 2018
• Last Update Posted: January 30, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Renal Cell Carcinoma	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Bevacizumab; Drug: Sunitinib	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 915 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: May 20, 2015
• Actual Primary Completion Date: February 14, 2020
• Actual Study Completion Date: December 13, 2021

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: 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.; Other Name: Tecentriq, MPDL3280A; Drug: 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.; Other Name: Avastin
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.	Drug: 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.; Other Name: Sutent

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Baseline 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.
2. Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected Population [ Time Frame: Baseline 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.
3. Percentage of Participants Who Died of Any Cause in ITT Population [ Time Frame: Baseline 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.
4. Overall Survival (OS) in ITT Population [ Time Frame: Baseline 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 :

1. Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population [ Time Frame: Baseline 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.
2. OS in PD-L1-Selected Population [ Time Frame: Baseline 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.
3. 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 [ Time Frame: Baseline 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.
4. PFS as Determined by an IRC According to RECIST v1.1 in ITT Population [ Time Frame: Baseline 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.
5. 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 [ Time Frame: Baseline 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.
6. PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected Population [ Time Frame: Baseline 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.
7. 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 [ Time Frame: Baseline 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.
8. Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable Population [ Time Frame: Baseline 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.
9. 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 [ Time Frame: Baseline 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.
10. DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable Population [ Time Frame: Baseline 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.
11. Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT Population [ Time Frame: Baseline 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.
12. PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT Population [ Time Frame: Baseline 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.
13. 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 [ Time Frame: Baseline 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.
14. DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable Population [ Time Frame: Baseline 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.
15. Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT Population [ Time Frame: Baseline 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.
16. PFS as Determined by the Investigator According to RECIST v1.1 in ITT Population [ Time Frame: Baseline 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.
17. 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 [ Time Frame: Baseline 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.
18. PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid Histology [ Time Frame: Baseline 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.
19. Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid Histology [ Time Frame: Baseline 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.
20. OS in Participants With Sarcomatoid Histology [ Time Frame: Baseline 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.
21. Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II Score [ Time Frame: 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 ]
    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.
22. Change From Baseline in Symptom Severity as Determined by MDASI Part I Score [ Time Frame: Baseline; 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.
23. Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale Score [ Time Frame: 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 ]
    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.
24. Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue Item [ Time Frame: 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 ]
    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.
25. 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 [ Time Frame: Day 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.
26. Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab [ Time Frame: 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) ]
    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.
27. Number of Participants With ATAs Against Bevacizumab [ Time Frame: 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) ]
    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.
28. Maximum Observed Serum Concentration (Cmax) for Atezolizumab [ Time Frame: 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) ]
    Cmax for atezolizumab was estimated from plasma concentration versus time data.
29. Minimum Observed Serum Concentration (Cmin) for Atezolizumab [ Time Frame: Predose (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.
30. Cmax for Bevacizumab [ Time Frame: 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) ]
    Cmax for bevacizumab was estimated from plasma concentration versus time data.
31. Cmin for Bevacizumab [ Time Frame: Pre-dose (Hour 0) on Day 1 of Cycle 3 (Cycle length = 42 days) ]
    Cmin for bevacizumab was estimated from plasma concentration versus time data.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Arizona

University of Arizona Cancer Center

Tucson, Arizona, United States, 85719

United States, California

University of California at Irvine Medical Center; Department of Oncology

Orange, California, United States, 92868

University of California

San Francisco, California, United States, 94158

United States, Colorado

University of Colorado; Anschutz Cancer Pavilion

Aurora, Colorado, United States, 80045

Rocky Mountain Cancer Center; Medical Oncology

Boulder, Colorado, United States, 80303

United States, District of Columbia

Georgetown U; Lombardi Comp Can

Washington, District of Columbia, United States, 20016-1468

United States, Florida

Lynn Cancer Institute/Boca Raton Regional Hospital

Boca Raton, Florida, United States, 33486

Florida Cancer Specialists - Port Charlotte

Port Charlotte, Florida, United States, 33980

Florida Cancer Specialist, North Region

Saint Petersburg, Florida, United States, 33705

United States, Georgia

Piedmont Cancer Institute, PC

Atlanta, Georgia, United States, 30318

United States, Illinois

The University of Chicago

Chicago, Illinois, United States, 60637

United States, Kentucky

Norton Cancer Institute

Louisville, Kentucky, United States, 40202

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Dana Farber Cancer Inst.

Boston, Massachusetts, United States, 02115

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

United States, Nevada

Comprehensive Cancer Centers of Nevada - Eastern Avenue

Las Vegas, Nevada, United States, 89169

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

New York Oncology Hematology,P.C.-Albany

Albany, New York, United States, 12208

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

United States, Ohio

Oncology Hematology Care Inc

Cincinnati, Ohio, United States, 45242

Cleveland Clinic Foundation; Taussig Cancer Center

Cleveland, Ohio, United States, 44195

United States, Oregon

Northwest Cancer Specialists, P.C.

Tigard, Oregon, United States, 97223

United States, Tennessee

SCRI Tennessee Oncology Chattanooga

Chattanooga, Tennessee, United States, 37404

Sarah Cannon Cancer Center and Research Institute

Nashville, Tennessee, United States, 37203

Vanderbilt Univ Medical Ctr

Nashville, Tennessee, United States, 37232

United States, Texas

Texas Oncology-Baylor Sammons Cancer Center

Dallas, Texas, United States, 75246

United States, Virginia

Oncology and Hematology Associates of SW Virginia-Raonoke

Roanoke, Virginia, United States, 24014

United States, Washington

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109

Australia, New South Wales

Lifehouse

Camperdown, New South Wales, Australia, 2050

Macquarie University Hospital

Macquarie Park, New South Wales, Australia, 2109

Calvary Mater Newcastle; Medical Oncology

Waratah, New South Wales, Australia, 2298

Australia, Queensland

Icon Cancer Foundation

South Brisbane, Queensland, Australia, 4101

Australia, South Australia

Ashford Cancer Center Research

Kurralta Park, South Australia, Australia, 5037

Australia, Victoria

Austin Hospital; Medical Oncology

Heidelberg, Victoria, Australia, 3084

Australia, Western Australia

St John of God Hospital

Murdoch, Western Australia, Australia, 6150

Bosnia and Herzegovina

University Clinical Centre of the Republic of Srpska

Banja Luka, Bosnia and Herzegovina, 78000

Brazil

Hospital de Caridade de Ijui; Oncologia

Ijui, RS, Brazil, 98700-000

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, RS, Brazil, 90050-170

Hospital Sao Lucas - PUCRS

Porto Alegre, RS, Brazil, 90610-000

Instituto do Cancer do Estado de Sao Paulo - ICESP

Sao Paulo, SP, Brazil, 01246-000

Canada, Nova Scotia

Queen Elizabeth II Health Sciences Centre; Oncology

Halifax, Nova Scotia, Canada, B3H 2Y9

Canada, Ontario

Royal Victoria Hospital

Barrie, Ontario, Canada, L4M 6M2

Hamilton Health Sciences - Juravinski Cancer Centre

Hamilton, Ontario, Canada, L8V 5C2

London Regional Cancer Centre

London, Ontario, Canada, N6A 4L6

Lakeridge Health Oshawa; Oncology

Oshawa, Ontario, Canada, L1G 2B9

The Ottawa Hospital Cancer Centre; Oncology

Ottawa, Ontario, Canada, K1H 8L6

Sunnybrook Odette Cancer Centre

Toronto, Ontario, Canada, M4N 3M5

Princess Margaret Cancer Center

Toronto, Ontario, Canada, M5G 1Z5

Canada, Quebec

Jewish General Hospital

Montreal, Quebec, Canada, H3T 1E2

CHU de Quebec Hotel-Dieu de Quebec

Quebec City, Quebec, Canada, G1R 2J6

Czechia

Masarykuv onkologicky ustav

Brno, Czechia, 656 53

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, Czechia, 779 00

Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika

Praha 2, Czechia, 128 08

Thomayerova nemocnice

Praha 4 - Krc, Czechia, 140 59

Denmark

Aarhus Universitetshospital; Kræftafdelingen

Aarhus N, Denmark, 8200

Herlev Hospital; Afdeling for Kræftbehandling

Herlev, Denmark, 2730

Odense Universitetshospital, Onkologisk Afdeling R

Odense C, Denmark, 5000

France

ICO Paul Papin; Oncologie Medicale.

Angers, France, 49055

Hopital Saint Andre; Oncologie 2

Bordeaux, France, 33075

Centre Francois Baclesse; Urologie Gynecologie

Caen, France, 14076

Centre Oscar Lambret

Lille, France, 59020

Centre Léon Bérard

Lyon, France, 69373

Institut Paoli Calmettes; Oncologie Medicale

Marseille, France, 13273

Centre D'Oncologie de Gentilly; Oncology

Nancy, France, 54100

APHP - Hospital Saint Louis

Paris, France, 75475

Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale

Paris, France, 75908

ICO - Site René Gauducheau

Saint Herblain, France, 44805

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, France, 94805

Germany

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

Dresden, Germany, 01307

Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung

Essen, Germany, 45122

Nationales Centrum für Tumorerkrankungen Heidelberg (NCT); Thoraxklinik Heidelberg

Heidelberg, Germany, 69120

Klinikum d.Universität München Campus Großhadern

München, Germany, 81377

Universitätsklinikum Tübingen; Klinik für Urologie

Tübingen, Germany, 72076

Italy

Az. Osp. Cardarelli; Divisione Di Oncologia

Napoli, Campania, Italy, 80131

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

Meldola, Emilia-Romagna, Italy, 47014

A.O. Universitaria Policlinico Di Modena; Oncologia

Modena, Emilia-Romagna, Italy, 41100

Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica

Roma, Lazio, Italy, 00152

Irccs Ospedale San Raffaele;Oncologia Medica

Milano, Lombardia, Italy, 20132

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

Milano, Lombardia, Italy, 20162

Fondazione IRCCS Policlinico San Matteo, Oncologia

Pavia, Lombardia, Italy, 27100

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

Arezzo, Toscana, Italy, 52100

Japan

Nagoya University Hospital; Urology

Aichi, Japan, 466-8560

Chiba Cancer Center

Chiba, Japan, 260-8717

Kyushu University Hospital

Fukuoka, Japan, 812-8582

Gunma University Hospital

Gunma, Japan, 371-8511

Hokkaido University Hospital

Hokkaido, Japan, 060-8648

University of Tsukuba Hospital; Urology

Ibaraki, Japan, 305-8576

Iwate Medical University Hospital

Iwate, Japan, 028-3695

Yokohama City University Hospital

Kanagawa, Japan, 236-0004

Kitasato University Hospital

Kanagawa, Japan, 252-0375

Kumamoto University Hospital

Kumamoto, Japan, 860-8556

Niigata University Medical & Dental Hospital

Niigata, Japan, 951-8520

Okayama University Hospital

Okayama, Japan, 700-8558

Osaka International Cancer Institute; Urology

Osaka, Japan, 541-8567

Osaka Metropolitan University Hospital

Osaka, Japan, 545-8586

Osaka University Hospital

Osaka, Japan, 565-0871

Kindai University Hospital

Osaka, Japan, 589-8511

Tokushima University Hospital

Tokushima, Japan, 770-8503

Toranomon Hospital

Tokyo, Japan, 105-8470

Tokyo Medical and Dental University Hospital

Tokyo, Japan, 113-8519

Nippon Medical School Hospital

Tokyo, Japan, 113-8603

The Cancer Institute Hospital, JFCR; Urology

Tokyo, Japan, 135-8550

Keio University Hospital

Tokyo, Japan, 160-8582

Tokyo Women's Medical University

Tokyo, Japan, 162-0054

Korea, Republic of

Chungnam National University Hospital

Daejeon, Korea, Republic of, 35015

National Cancer Center

Goyang-si, Korea, Republic of, 10408

Seoul National University Bundang Hospital

Seongnam-si, Korea, Republic of, 13620

Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 003-722

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Asan Medical Center

Seoul, Korea, Republic of, 05505

Samsung Medical Center

Seoul, Korea, Republic of, 135-710

Mexico

Cancerología

Queretaro, Mexico, 76090

Centro Oncologico Estatal ISSEMYM

Toluca, Mexico, 50180

Poland

Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli

Lublin, Poland, 20-090

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

Poznan, Poland, 60-569

Saint Elizabeth's Hospital

Warsaw, Poland, 02-616

MAGODENT Sp. z o.o.

Warsaw, Poland, 04-125

Russian Federation

ALTAI REGIONAL ONCOLOGICAL CENTER; "Nadezhda" Clinic

Barnaul, Altaj, Russian Federation, 656049

GBUZ Nizhegorodskay Region: Clinical Diagnostic Center

Nizhni Novgorod, Niznij Novgorod, Russian Federation, 603001

P.A. Herzen Oncological Inst. ; Oncology

Moscow, Russian Federation, 125284

City Clinical Oncology Hospital

Moscow, Russian Federation, 143423

Singapore

National University Hospital

Singapore, Singapore, 117599

National Cancer Centre; Medical Oncology

Singapore, Singapore, 169610

Spain

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, Spain, 8208

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, Spain, 14004

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, Spain, 08035

Hospital Clínic i Provincial; Servicio de Oncología

Barcelona, Spain, 08036

Hospital Duran i Reynals; Oncologia

Barcelona, Spain, 08907

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, Spain, 28007

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, Spain, 28034

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, Spain, 28041

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Sevilla, Spain, 41013

Taiwan

Taichung Veterans General Hospital; Division of Urology

Taichung, Taiwan, 407

National Taiwan Uni Hospital; Dept of Oncology

Taipei, Taiwan, 100

Chang Gung Medical Foundation-Linkou, Urinary Oncology

Taoyuan, Taiwan, 333

Thailand

Chulalongkorn Hospital; Medical Oncology

Bangkok, Thailand, 10330

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

Bangkok, Thailand, 10400

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

Bangkok, Thailand, 10700

Maharaj Nakorn Chiangmai Hospital; Department of Surgery/ Urology unit

Chiangmai, Thailand, 50200

Songklanagarind Hospital; Department of Oncology

Songkhla, Thailand, 90110

Turkey

Hacettepe University Medical Faculty

Ankara, Turkey, 06100

Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department

Edirne, Turkey, 22770

Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology

Istanbul, Turkey, 34300

United Kingdom

Clatterbridge Cancer Centre

Bebington, United Kingdom, CH63 4JY

Queen Elizabeth Hospital

Birmingham, United Kingdom, B15 2TH

Royal Blackburn Hospital

Blackburn, United Kingdom, BB2 3HH

Addenbrookes Nhs Trust; Oncology Clinical Trials Unit

Cambridge, United Kingdom, CB2 0QQ

Barts Health NHS Trust - St Bartholomew's Hospital

London, United Kingdom, EC1A 7BE

Royal Free Hospital; Dept of Oncology

London, United Kingdom, NW3 2QG

Christie Hospital Nhs Trust; Medical Oncology

Manchester, United Kingdom, M2O 4BX

Churchill Hospital; Oxford Cancer and Haematology Centre

Oxford, United Kingdom, OX3 7LJ

Southampton General Hospital; Medical Oncology

Southampton, United Kingdom, SO16 6YD

Royal Marsden Hospital; Dept of Medical Oncology

Sutton, United Kingdom, SM2 5PT

Singleton Hospital; Pharmacy Department

Swansea, United Kingdom, SA2 8QA

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:

Study Protocol and Statistical Analysis Plan  [PDF] April 3, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Motzer RJ, Powles T, Atkins MB, Escudier B, McDermott DF, Alekseev BY, Lee JL, Suarez C, Stroyakovskiy D, De Giorgi U, Donskov F, Mellado B, Banchereau R, Hamidi H, Khan O, Craine V, Huseni M, Flinn N, Dubey S, Rini BI. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2022 Feb 1;8(2):275-280. doi: 10.1001/jamaoncol.2021.5981.

Atkins MB, Rini BI, Motzer RJ, Powles T, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Gurney H, Oudard S, Uemura M, Lam ET, Grullich C, Quach C, Carroll S, Ding B, Zhu QC, Piault-Louis E, Schiff C, Escudier B. Patient-Reported Outcomes from the Phase III Randomized IMmotion151 Trial: Atezolizumab + Bevacizumab versus Sunitinib in Treatment-Naive Metastatic Renal Cell Carcinoma. Clin Cancer Res. 2020 Jun 1;26(11):2506-2514. doi: 10.1158/1078-0432.CCR-19-2838. Epub 2020 Mar 3.

Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ; IMmotion151 Study Group. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019 Jun 15;393(10189):2404-2415. doi: 10.1016/S0140-6736(19)30723-8. Epub 2019 May 9.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02420821
• Other Study ID Numbers: WO29637; 2014-004684-20 ( EudraCT Number )
• First Posted: April 20, 2015
• Results First Posted: October 3, 2018
• Last Update Posted: January 30, 2023
• Last Verified: January 2023

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Bevacizumab; Atezolizumab; Sunitinib; Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Immunologic Factors; Immune Checkpoint Inhibitors