A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) as Monotherapy or in Combination With Bevacizumab (Avastin®) Compared to Sunitinib (Sutent®) in Participants With Untreated Advanced Renal Cell Carcinoma

Renal Cell Carcinoma Clinical Trial

— IMmotion150  

Official title:

A Phase II, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Administered as Monotherapy or in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01984242
• Other study ID #: WO29074
• Secondary ID: 2013-003167-58
• Status: Completed
• Phase: Phase 2
• Start date: January 8, 2014
• Est. completion date: January 8, 2019

Study information

• Verified date: December 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multicenter, randomized, open-label study will evaluate the efficacy, safety and tolerability of atezolizumab as monotherapy or in combination with bevacizumab versus sunitinib in participants with histologically confirmed, inoperable, locally advanced or metastatic renal cell carcinoma who have not received prior systemic therapy either in the adjuvant or metastatic setting.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 305
• Est. completion date: January 8, 2019
• Est. primary completion date: October 17, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Unresectable advanced or metastatic renal cell carcinoma with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agents, including treatment in the adjuvant setting

• Measurable disease, as defined by RECIST v1.1

• Karnofsky performance score greater than or equal to (>/=) 70

• Adequate hematologic and end-organ function as defined by protocol

• Women of childbearing potential and male participants with partners of childbearing potential must agree to use highly effective methods of contraception as defined by protocol

Exclusion Criteria:

Disease-Specific Exclusions:

• Radiotherapy for renal cell carcinoma within 14 days prior to Cycle 1, Day 1 with the exception of single-fraction radiotherapy given for the indication of pain control

• Known active malignancies or metastasis of the brain or spinal cord or leptomeningeal disease, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)

• Uncontrolled hypercalcemia or symptomatic hypercalcemia

• Malignancies other than renal cell carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death, treated with expected curative outcome

General Medical Exclusions:

• Life expectancy of less than (<) 12 weeks

• Pregnant and lactating women

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

• History of autoimmune disease

• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan

• Participants with active or chronic hepatitis B, active hepatitis C, Human Immunodeficiency Virus (HIV) positive test, significant cardiovascular disease

• Prior allogeneic stem cell or solid organ transplant

Exclusion Criteria Related to Medications:

• Prior treatment with Cluster of Differentiation 137 (CD137) agonists, anti-Cytotoxic T-Lymphocyte Antigen-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents

• Treatment with systemic immunostimulatory agents for any reason within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1

• Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1

Bevacizumab- and Sunitinib-Specific Exclusions:

• Inadequately controlled hypertension

• Prior history of hypertensive crisis or hypertensive encephalopathy

• New York Heart Association Class II or greater congestive heart failure

• History of myocardial infarction or unstable angina, stroke or transient ischemic attack within 3 months prior to Cycle 1, Day 1

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.
• Bevacizumab
Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.
• Sunitinib
Sunitinib will be administered according to the dosage schedule mentioned in the arm description.

Locations

Country	Name	City	State
Czechia	Fakultni nemocnice Olomouc	Olomouc
France	Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale	Paris
France	CHU Bordeaux	Pessac
France	Institut Gustave Roussy; Departement Oncologie Medicale	Villejuif
Germany	Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie	Hannover
Germany	Klinikum rechts der Isar der TU München; Klinikapotheke	Muenchen
Germany	Klinikum d.Universität München Campus Großhadern	München
Italy	Medical Oncology, Arezzo	Arezzo	Toscana
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2	Milano	Lombardia
Italy	Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica	Siena	Toscana
Poland	Centrum Med. Ostrobramska NZOZ Magodent	Warszawa
Romania	Prof. Dr. I. Chiricuta Institute of Oncology	Cluj Napoca
Romania	Medisprof SRL	Cluj-Napoca
Spain	Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
United Kingdom	Barts and the London NHS Trust.	London
United Kingdom	Royal Marsden Hospital - London	London
United Kingdom	Christie Hospital Nhs Trust; Medical Oncology	Manchester
United States	Univ Colorado Health Sci Ctr	Aurora	Colorado
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Inst.	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of Chicago	Chicago	Illinois
United States	Oncology Hematology Care Inc	Cincinnati	Ohio
United States	Cleveland Clinic Foundation; Taussig Cancer Center	Cleveland	Ohio
United States	Texas Oncology-Baylor Sammons Cancer Center	Dallas	Texas
United States	Rocky Mountain Cancer Ctr - Denver (Williams)	Denver	Colorado
United States	Karmanos Cancer Institute.	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Oncology Associates of Oregon, P.C	Eugene	Oregon
United States	SCRI Florida Cancer Specialists South	Fort Myers	Florida
United States	Mayo Clinic-Jacksonville	Jacksonville	Florida
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	UCLA	Los Angeles	California
United States	Tennessee Oncology PLLC - Nashville (20th Ave)	Nashville	Tennessee
United States	Vanderbilt Medical Center	Nashville	Tennessee
United States	Yale Uni School of Medicine; Section of Medical Oncology	New Haven	Connecticut
United States	Memorial Sloan-Kettering	New York	New York
United States	Florida Cancer Specialist, North Region	Saint Petersburg	Florida
United States	University of California	San Francisco	California
United States	HonorHealth Research Institute - Bisgrove	Scottsdale	Arizona
United States	Northwest Cancer Specialists, P.C.	Tigard	Oregon
United States	Georgetown U; Lombardi Comp Can	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Czechia,  France,  Germany,  Italy,  Poland,  Romania,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	EuroQoL 5 Dimension (EQ-5D) Questionnaire Score	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.	Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)
Primary	Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population	Progressive Disease (PD): at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm); appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Primary	Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Primary	Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Primary	PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to less than (<) 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population	PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	PFS Per Modified RECIST Via Investigator Assessment in ITT Population	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population	PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	DOR Per Modified RECIST Via Investigator Assessment in ITT Population	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants Who Died in ITT Population		Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Overall Survival (OS) in ITT Population	OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.	Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants Who Died in IC1/2/3 Population		Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	OS in IC1/2/3 Population	OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.	Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.	From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.	From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.	From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.	From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Secondary	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab	This outcome measure was planned to be analyzed in 'Atezolizumab' and 'Atezolizumab and Bevacizumab' arms only.	Cycle 1 Day 1 until treatment discontinuation (until data cut-off date 17 October 2016, up to approximately 2.75 years) (1 cycle=6 weeks)
Secondary	Maximum Serum Concentration (Cmax) of Atezolizumab		30 minutes after end of infusion on Cycle 1 Day 1 (1 cycle=6 weeks) (infusion length for first dose=60 minutes)
Secondary	Minimum Serum Concentration (Cmin) of Atezolizumab		Pre-infusion (0 hour) on Day 1 of Cycles 2 and 4; Day 22 of Cycles 1, 2, and 4 (1 cycle=6 weeks) (infusion length=30-60 minutes)
Secondary	Cmax of Bevacizumab		30 minutes after end of infusion on Day 1 of Cycles 1 and 2 (1 cycle=6 weeks) (infusion length=30-90 minutes)
Secondary	Cmin of Bevacizumab		For Atezolizumab and Bevacizumab Arm: at First-line treatment discontinuation (up to approximately 2.75 years); For Crossover Arms: pre-infusion (0 hour) on Day 1 of Cycle 2 (1 cycle=6 weeks) (infusion length=30-90 minutes)
Secondary	M.D. Anderson Symptom Inventory (MDASI) Interference Score	MDASI questionnaire comprises of 2 parts: symptoms (16 items), interference with daily life (6 items). Participants were asked to rate how much their symptoms interfered with general activity, mood, work, relations with other people, walking, and enjoyment of life during the last 24 hours. Each item in the interference score was answered on a scale of 0 (did not interfere) to 10 (interfered completely). The mean score of all 6 items was reported on the scale of 0 (did not interfere) to 10 (interfered completely).	Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)
Secondary	Brief Fatigue Inventory (BFI) Fatigue Level Score	BFI questionnaire comprises of 2 parts: fatigue level (3 items), interference with daily life (1 item with 6 sub-items). Each items in the fatigue level score was answered on a scale of 0 (no fatigue) to 10 (as bad as you can imagine). The mean score of all 3 items was reported on the scale of 0 (no fatigue) to 10 (as bad as you can imagine).	Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)