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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Bevacizumab; Drug: Sunitinib

• Study Type: Interventional
• Enrollment (Actual): 915
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Lifehouse
    • Macquarie Park, New South Wales, Australia, 2109
      • Macquarie University Hospital
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle; Medical Oncology
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Foundation
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Ashford Cancer Center Research
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital; Medical Oncology
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • St John of God Hospital
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • University Clinical Centre of the Republic of Srpska
• Brazil
  • RS
    • Ijui, RS, Brazil, 98700-000
      • Hospital de Caridade de Ijui; Oncologia
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
    • Porto Alegre, RS, Brazil, 90050-170
      • Santa Casa de Misericordia de Porto Alegre
  • SP
    • Sao Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Centre; Oncology
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital
    • Hamilton, Ontario, Canada, L8V 5C2
      • Hamilton Health Sciences - Juravinski Cancer Centre
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Centre
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa; Oncology
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre; Oncology
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Center
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Odette Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHU de Quebec Hotel-Dieu de Quebec
• Czechia
  • Brno, Czechia, 656 53
    • Masarykuv onkologicky ustav
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc; Onkologicka klinika
  • Praha 2, Czechia, 128 08
    • Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika
  • Praha 4 - Krc, Czechia, 140 59
    • Thomayerova nemocnice
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital; Kræftafdelingen
  • Herlev, Denmark, 2730
    • Herlev Hospital; Afdeling for Kræftbehandling
  • Odense C, Denmark, 5000
    • Odense Universitetshospital, Onkologisk Afdeling R
• France
  • Angers, France, 49055
    • ICO Paul Papin; Oncologie Medicale.
  • Bordeaux, France, 33075
    • Hopital Saint Andre; Oncologie 2
  • Caen, France, 14076
    • Centre Francois Baclesse; Urologie Gynecologie
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69373
    • Centre Leon Berard
  • Marseille, France, 13273
    • Institut Paoli Calmettes; Oncologie Medicale
  • Nancy, France, 54100
    • Centre D'Oncologie de Gentilly; Oncology
  • Paris, France, 75475
    • APHP - Hospital Saint Louis
  • Paris, France, 75908
    • Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale
  • Saint Herblain, France, 44805
    • ICO - Site René Gauducheau
  • Villejuif, France, 94805
    • Institut Gustave Roussy; Departement Oncologie Medicale
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie
  • Essen, Germany, 45122
    • Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung
  • Heidelberg, Germany, 69120
    • Nationales Centrum für Tumorerkrankungen Heidelberg (NCT); Thoraxklinik Heidelberg
  • München, Germany, 81377
    • Klinikum d.Universität München Campus Großhadern
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen; Klinik für Urologie
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Az. Osp. Cardarelli; Divisione Di Oncologia
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
    • Modena, Emilia-Romagna, Italy, 41100
      • A.O. Universitaria Policlinico Di Modena; Oncologia
  • Lazio
    • Roma, Lazio, Italy, 00152
      • Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica
  • Lombardia
    • Milano, Lombardia, Italy, 20162
      • Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
    • Milano, Lombardia, Italy, 20132
      • Irccs Ospedale San Raffaele;Oncologia Medica
    • Pavia, Lombardia, Italy, 27100
      • Fondazione IRCCS Policlinico San Matteo, Oncologia
  • Toscana
    • Arezzo, Toscana, Italy, 52100
      • Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia
• Japan
  • Aichi, Japan, 466-8560
    • Nagoya University Hospital; Urology
  • Chiba, Japan, 260-8717
    • Chiba Cancer Center
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Gunma, Japan, 371-8511
    • Gunma University Hospital
  • Hokkaido, Japan, 060-8648
    • Hokkaido University Hospital
  • Ibaraki, Japan, 305-8576
    • University of Tsukuba Hospital; Urology
  • Iwate, Japan, 028-3695
    • Iwate Medical University Hospital
  • Kanagawa, Japan, 252-0375
    • Kitasato University Hospital
  • Kanagawa, Japan, 236-0004
    • Yokohama City University Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Niigata, Japan, 951-8520
    • Niigata University Medical & Dental Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Osaka, Japan, 565-0871
    • Osaka University Hospital
  • Osaka, Japan, 589-8511
    • Kindai University Hospital
  • Osaka, Japan, 545-8586
    • Osaka Metropolitan University Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute; Urology
  • Tokushima, Japan, 770-8503
    • Tokushima University Hospital
  • Tokyo, Japan, 160-8582
    • Keio University Hospital
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital
  • Tokyo, Japan, 113-8519
    • Tokyo Medical and Dental University Hospital
  • Tokyo, Japan, 162-0054
    • Tokyo Women's Medical University
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital, JFCR; Urology
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35015
    • Chungnam National University Hospital
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 003-722
    • Severance Hospital, Yonsei University Health System
• Mexico
  • Queretaro, Mexico, 76090
    • Cancerología
  • Toluca, Mexico, 50180
    • Centro Oncologico Estatal ISSEMYM
• Poland
  • Lublin, Poland, 20-090
    • Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli
  • Poznan, Poland, 60-569
    • Szpital Kliniczny; Przemienienia Panskiego;Uniwersytetu Medyczny im.; Karola Marcinkowskiego w Pozna
  • Warsaw, Poland, 04-125
    • Magodent Sp. Z o.o.
  • Warsaw, Poland, 02-616
    • Saint Elizabeth's Hospital
• Russian Federation
  • Moscow, Russian Federation, 143423
    • City Clinical Oncology Hospital
  • Moscow, Russian Federation, 125284
    • P.A. Herzen Oncological Inst. ; Oncology
  • Altaj
    • Barnaul, Altaj, Russian Federation, 656049
      • ALTAI REGIONAL ONCOLOGICAL CENTER; "Nadezhda" Clinic
  • Niznij Novgorod
    • Nizhni Novgorod, Niznij Novgorod, Russian Federation, 603001
      • GBUZ Nizhegorodskay Region: Clinical Diagnostic Center
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre; Medical Oncology
  • Singapore, Singapore, 117599
    • National University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Barcelona, Spain, 08907
    • Hospital Duran i Reynals; Oncologia
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial; Servicio de Oncología
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
  • Barcelona
    • Sabadell, Barcelona, Spain, 8208
      • Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
  • Cordoba
    • Córdoba, Cordoba, Spain, 14004
      • Hospital Universitario Reina Sofia; Servicio de Oncologia
• Taiwan
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital; Division of Urology
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital; Dept of Oncology
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation-Linkou, Urinary Oncology
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn Hospital; Medical Oncology
  • Bangkok, Thailand, 10700
    • Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
  • Chiangmai, Thailand, 50200
    • Maharaj Nakorn Chiangmai Hospital; Department of Surgery/ Urology unit
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital; Department of Oncology
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty
  • Edirne, Turkey, 22770
    • Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
  • Istanbul, Turkey, 34300
    • Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology
• United Kingdom
  • Bebington, United Kingdom, CH63 4JY
    • Clatterbridge Cancer Centre
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Blackburn, United Kingdom, BB2 3HH
    • Royal Blackburn Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrookes Nhs Trust; Oncology Clinical Trials Unit
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital; Dept of Oncology
  • London, United Kingdom, EC1A 7BE
    • Barts Health NHS Trust - St Bartholomew's Hospital
  • Manchester, United Kingdom, M2O 4BX
    • Christie Hospital Nhs Trust; Medical Oncology
  • Oxford, United Kingdom, OX3 7LJ
    • Churchill Hospital; Oxford Cancer and Haematology Centre
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital; Medical Oncology
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital; Dept of Medical Oncology
  • Swansea, United Kingdom, SA2 8QA
    • Singleton Hospital; Pharmacy Department
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center
  • California
    • Orange, California, United States, 92868
      • University of California at Irvine Medical Center; Department of Oncology
    • San Francisco, California, United States, 94158
      • University of California
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado; Anschutz Cancer Pavilion
    • Boulder, Colorado, United States, 80303
      • Rocky Mountain Cancer Center; Medical Oncology
  • District of Columbia
    • Washington, District of Columbia, United States, 20016-1468
      • Georgetown U; Lombardi Comp Can
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute/Boca Raton Regional Hospital
    • Port Charlotte, Florida, United States, 33980
      • Florida Cancer Specialists - Port Charlotte
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialist, North Region
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Piedmont Cancer Institute, PC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Inst.
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada - Eastern Avenue
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology,P.C.-Albany
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation; Taussig Cancer Center
  • Oregon
    • Tigard, Oregon, United States, 97223
      • Northwest Cancer Specialists, P.C.
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • SCRI Tennessee Oncology Chattanooga
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center and Research Institute
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Univ Medical Ctr
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Sammons Cancer Center
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Oncology and Hematology Associates of SW Virginia-Raonoke
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: Sutent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Percentage of Participants Who Died of Any Cause in ITT Population	Percentage of participants who died of any cause was reported.	Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)
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.	Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	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 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.	Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	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 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.	Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
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.	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
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.	Baseline; End of Treatment (EoT) visit (up to approximately 27 months)
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.	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
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.	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
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.	Day 1 and 22 of every cycle (Baseline = Day 1 Cycle 1) up to Cycle 19; Cycle length = 42 days
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.	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)
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.	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)
Maximum Observed Serum Concentration (Cmax) for Atezolizumab	Cmax for atezolizumab was estimated from plasma concentration versus time data.	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)
Minimum Observed Serum Concentration (Cmin) for Atezolizumab	Cmin for atezolizumab was estimated from plasma concentration versus time data.	Predose (Hour 0) on Day 22 of Cycle 1; predose (Hour 0) on Day 1 of Cycles 2; Cycle length = 42 days
Cmax for Bevacizumab	Cmax for bevacizumab was estimated from plasma concentration versus time data.	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)
Cmin for Bevacizumab	Cmin for bevacizumab was estimated from plasma concentration versus time data.	Pre-dose (Hour 0) on Day 1 of Cycle 3 (Cycle length = 42 days)
Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population	Percentage of participants who died of any cause was reported.	Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)
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.	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 in Participants With Sarcomatoid Histology	Percentage of participants with sarcomatoid histology who died of any cause was reported.	Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)
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.	Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2015
• Primary Completion (Actual): February 14, 2020
• Study Completion (Actual): December 13, 2021

Study Registration Dates

• First Submitted: April 15, 2015
• First Submitted That Met QC Criteria: April 15, 2015
• First Posted (Estimate): April 20, 2015

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 4, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Antibodies; Sunitinib; Bevacizumab; Antibodies, Monoclonal; Atezolizumab
• Other Study ID Numbers: WO29637; 2014-004684-20 (EudraCT Number)