Back to resultsA 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 (IMmotion150)
Primary Purpose
Renal Cell Carcinoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
Bevacizumab
Sunitinib
Sponsored by
About this trial
This is an interventional treatment trial for Renal Cell Carcinoma
Eligibility Criteria
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
Sites / Locations
- HonorHealth Research Institute - Bisgrove
- City of Hope Comprehensive Cancer Center
- UCLA
- University of California
- Univ Colorado Health Sci Ctr
- Rocky Mountain Cancer Ctr - Denver (Williams)
- Yale Uni School of Medicine; Section of Medical Oncology
- Georgetown U; Lombardi Comp Can
- SCRI Florida Cancer Specialists South
- Mayo Clinic-Jacksonville
- Florida Cancer Specialist, North Region
- The University of Chicago
- Massachusetts General Hospital
- Dana Farber Cancer Inst.
- Beth Israel Deaconess Medical Center
- Karmanos Cancer Institute.
- Comprehensive Cancer Centers of Nevada
- Memorial Sloan-Kettering
- Oncology Hematology Care Inc
- Cleveland Clinic Foundation; Taussig Cancer Center
- Oncology Associates of Oregon, P.C
- Northwest Cancer Specialists, P.C.
- Tennessee Oncology PLLC - Nashville (20th Ave)
- Vanderbilt Medical Center
- Texas Oncology-Baylor Sammons Cancer Center
- Fakultni nemocnice Olomouc
- Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale
- CHU Bordeaux
- Institut Gustave Roussy; Departement Oncologie Medicale
- Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
- Klinikum rechts der Isar der TU München; Klinikapotheke
- Klinikum d.Universität München Campus Großhadern
- Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
- Medical Oncology, Arezzo
- Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
- Centrum Med. Ostrobramska NZOZ Magodent
- Prof. Dr. I. Chiricuta Institute of Oncology
- Medisprof SRL
- Clinica Universitaria de Navarra
- Hospital Universitari Vall d'Hebron
- Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department
- Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal
- Barts and the London NHS Trust.
- Royal Marsden Hospital - London
- Christie Hospital Nhs Trust; Medical Oncology
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Atezolizumab and Bevacizumab
Atezolizumab
Sunitinib
Arm Description
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) will be administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
Atezolizumab 1200 mg will be administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except European Union [EU] participants) can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Sunitinib 50 mg will be administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Percentage of Participants Who Died in ITT Population
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.
Percentage of Participants Who Died in IC1/2/3 Population
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.
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.
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.
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.
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.
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.
Maximum Serum Concentration (Cmax) of Atezolizumab
Minimum Serum Concentration (Cmin) of Atezolizumab
Cmax of Bevacizumab
Cmin of Bevacizumab
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).
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01984242
Brief Title
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
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
January 8, 2014 (Actual)
Primary Completion Date
October 17, 2016 (Actual)
Study Completion Date
January 8, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
305 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Atezolizumab and Bevacizumab
Arm Type
Experimental
Arm Description
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) will be administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
Arm Title
Atezolizumab
Arm Type
Experimental
Arm Description
Atezolizumab 1200 mg will be administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except European Union [EU] participants) can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Arm Title
Sunitinib
Arm Type
Active Comparator
Arm Description
Sunitinib 50 mg will be administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
Other Intervention Name(s)
Tecentriq, MPDL3280A, RO5541267
Intervention Description
Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.
Intervention Type
Drug
Intervention Name(s)
Sunitinib
Other Intervention Name(s)
Sutent
Intervention Description
Sunitinib will be administered according to the dosage schedule mentioned in the arm description.
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
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)
Title
Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population
Description
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.
Time Frame
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)
Title
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
Description
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.
Time Frame
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)
Title
PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
Description
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.
Time Frame
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 Outcome Measure Information:
Title
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
Description
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.
Time Frame
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)
Title
PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
Description
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.
Time Frame
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)
Title
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
Description
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.
Time Frame
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)
Title
PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
Description
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.
Time Frame
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)
Title
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
Description
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.
Time Frame
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)
Title
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
Description
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.
Time Frame
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)
Title
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
Description
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.
Time Frame
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)
Title
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
Description
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.
Time Frame
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)
Title
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population
Description
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.
Time Frame
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)
Title
PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population
Description
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.
Time Frame
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)
Title
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population
Description
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.
Time Frame
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)
Title
PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
Description
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.
Time Frame
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)
Title
Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population
Description
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.
Time Frame
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)
Title
Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
Description
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.
Time Frame
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)
Title
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population
Description
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.
Time Frame
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)
Title
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
Description
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.
Time Frame
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)
Title
Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population
Description
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.
Time Frame
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)
Title
Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
Description
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.
Time Frame
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)
Title
Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population
Description
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.
Time Frame
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)
Title
PFS Per Modified RECIST Via Investigator Assessment in ITT Population
Description
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.
Time Frame
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)
Title
Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population
Description
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.
Time Frame
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)
Title
PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
Description
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.
Time Frame
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)
Title
Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population
Description
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.
Time Frame
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)
Title
DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population
Description
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.
Time Frame
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)
Title
DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
Description
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.
Time Frame
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)
Title
DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
Description
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.
Time Frame
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)
Title
DOR Per Modified RECIST Via Investigator Assessment in ITT Population
Description
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.
Time Frame
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)
Title
DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
Description
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.
Time Frame
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)
Title
Percentage of Participants Who Died in ITT Population
Time Frame
Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Title
Overall Survival (OS) in ITT Population
Description
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.
Time Frame
Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Title
Percentage of Participants Who Died in IC1/2/3 Population
Time Frame
Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Title
OS in IC1/2/3 Population
Description
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.
Time Frame
Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Title
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population
Description
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.
Time Frame
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)
Title
DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population
Description
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.
Time Frame
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)
Title
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population
Description
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.
Time Frame
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)
Title
PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population
Description
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.
Time Frame
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)
Title
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab
Description
This outcome measure was planned to be analyzed in 'Atezolizumab' and 'Atezolizumab and Bevacizumab' arms only.
Time Frame
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)
Title
Maximum Serum Concentration (Cmax) of Atezolizumab
Time Frame
30 minutes after end of infusion on Cycle 1 Day 1 (1 cycle=6 weeks) (infusion length for first dose=60 minutes)
Title
Minimum Serum Concentration (Cmin) of Atezolizumab
Time Frame
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)
Title
Cmax of Bevacizumab
Time Frame
30 minutes after end of infusion on Day 1 of Cycles 1 and 2 (1 cycle=6 weeks) (infusion length=30-90 minutes)
Title
Cmin of Bevacizumab
Time Frame
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)
Title
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Description
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).
Time Frame
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)
Title
Brief Fatigue Inventory (BFI) Fatigue Level Score
Description
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).
Time Frame
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)
Other Pre-specified Outcome Measures:
Title
EuroQoL 5 Dimension (EQ-5D) Questionnaire Score
Description
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.
Time Frame
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
HonorHealth Research Institute - Bisgrove
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
University of California
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Univ Colorado Health Sci Ctr
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rocky Mountain Cancer Ctr - Denver (Williams)
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Yale Uni School of Medicine; Section of Medical Oncology
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510-3289
Country
United States
Facility Name
Georgetown U; Lombardi Comp Can
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20016-1468
Country
United States
Facility Name
SCRI Florida Cancer Specialists South
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33916
Country
United States
Facility Name
Mayo Clinic-Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Florida Cancer Specialist, North Region
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33705
Country
United States
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Inst.
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Karmanos Cancer Institute.
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
Memorial Sloan-Kettering
City
New York
State/Province
New York
Country
United States
Facility Name
Oncology Hematology Care Inc
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
Cleveland Clinic Foundation; Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Oncology Associates of Oregon, P.C
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Northwest Cancer Specialists, P.C.
City
Tigard
State/Province
Oregon
ZIP/Postal Code
97223
Country
United States
Facility Name
Tennessee Oncology PLLC - Nashville (20th Ave)
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Vanderbilt Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-7610
Country
United States
Facility Name
Texas Oncology-Baylor Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Fakultni nemocnice Olomouc
City
Olomouc
ZIP/Postal Code
775 20
Country
Czechia
Facility Name
Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale
City
Paris
ZIP/Postal Code
75908
Country
France
Facility Name
CHU Bordeaux
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Institut Gustave Roussy; Departement Oncologie Medicale
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Klinikum rechts der Isar der TU München; Klinikapotheke
City
Muenchen
ZIP/Postal Code
81675
Country
Germany
Facility Name
Klinikum d.Universität München Campus Großhadern
City
München
ZIP/Postal Code
81377
Country
Germany
Facility Name
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
Facility Name
Medical Oncology, Arezzo
City
Arezzo
State/Province
Toscana
ZIP/Postal Code
52100
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
City
Siena
State/Province
Toscana
ZIP/Postal Code
53100
Country
Italy
Facility Name
Centrum Med. Ostrobramska NZOZ Magodent
City
Warszawa
ZIP/Postal Code
04-125
Country
Poland
Facility Name
Prof. Dr. I. Chiricuta Institute of Oncology
City
Cluj Napoca
ZIP/Postal Code
400015
Country
Romania
Facility Name
Medisprof SRL
City
Cluj-Napoca
ZIP/Postal Code
400058
Country
Romania
Facility Name
Clinica Universitaria de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Barts and the London NHS Trust.
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Name
Royal Marsden Hospital - London
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
Christie Hospital Nhs Trust; Medical Oncology
City
Manchester
ZIP/Postal Code
M2O 4BX
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
32233107
Citation
Pal SK, McDermott DF, Atkins MB, Escudier B, Rini BI, Motzer RJ, Fong L, Joseph RW, Oudard S, Ravaud A, Bracarda S, Suarez C, Lam ET, Choueiri TK, Ding B, Quach C, Hashimoto K, Schiff C, Piault-Louis E, Powles T. Patient-reported outcomes in a phase 2 study comparing atezolizumab alone or with bevacizumab vs sunitinib in previously untreated metastatic renal cell carcinoma. BJU Int. 2020 Jul;126(1):73-82. doi: 10.1111/bju.15058. Epub 2020 Apr 24.
Results Reference
derived
Learn more about this trial
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
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