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
- Conditions
- Renal Cell Carcinoma
- Interventions
- Registration Number
- NCT01984242
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 305
- 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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody 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. Atezolizumab and Bevacizumab Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody 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. Sunitinib Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody 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. Sunitinib Sunitinib 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. Atezolizumab and Bevacizumab Bevacizumab 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 Bevacizumab 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 Bevacizumab 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.
- Primary Outcome Measures
Name Time Method 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 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) 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.
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 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) 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 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) 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.
PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population 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) 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
Name Time Method PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature 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) 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 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) 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 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) 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.
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 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) 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 Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population 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) 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 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 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) 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.
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population 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) 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.
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 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) 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 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) 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 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) 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 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) 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 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) 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 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) 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 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) 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 Investigator Assessment in ITT Population 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) 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 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) 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 Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population 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) 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.
Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population 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) 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 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) 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.
PFS Per Modified RECIST Via Investigator Assessment in ITT Population 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) 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 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) 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.
Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population 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) 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 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) 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 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) 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 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) 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 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) 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 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) 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 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) 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.
OS 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) 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.
Overall Survival (OS) in ITT Population Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) 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 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) 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.
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) 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) 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) DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population 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) 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 Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population 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) 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.
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) M.D. Anderson Symptom Inventory (MDASI) Interference Score 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) 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).
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) PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population 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) 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 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) This outcome measure was planned to be analyzed in 'Atezolizumab' and 'Atezolizumab and Bevacizumab' arms only.
Brief Fatigue Inventory (BFI) Fatigue Level Score 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) 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).
Trial Locations
- Locations (45)
The University of Chicago
🇺🇸Chicago, Illinois, United States
Texas Oncology-Baylor Sammons Cancer Center
🇺🇸Dallas, Texas, United States
University of California
🇺🇸San Francisco, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Inst.
🇺🇸Boston, Massachusetts, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Oncology Hematology Care Inc
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic Foundation; Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Tennessee Oncology PLLC - Nashville (20th Ave)
🇺🇸Nashville, Tennessee, United States
Vanderbilt Medical Center
🇺🇸Nashville, Tennessee, United States
SCRI Florida Cancer Specialists South
🇺🇸Fort Myers, Florida, United States
Mayo Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
HonorHealth Research Institute - Bisgrove
🇺🇸Scottsdale, Arizona, United States
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Karmanos Cancer Institute.
🇺🇸Detroit, Michigan, United States
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
🇮🇹Milano, Lombardia, Italy
Christie Hospital Nhs Trust; Medical Oncology
🇬🇧Manchester, United Kingdom
Royal Marsden Hospital - London
🇬🇧London, United Kingdom
UCLA
🇺🇸Los Angeles, California, United States
Rocky Mountain Cancer Ctr - Denver (Williams)
🇺🇸Denver, Colorado, United States
Florida Cancer Specialist, North Region
🇺🇸Saint Petersburg, Florida, United States
Univ Colorado Health Sci Ctr
🇺🇸Aurora, Colorado, United States
Yale Uni School of Medicine; Section of Medical Oncology
🇺🇸New Haven, Connecticut, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Memorial Sloan-Kettering
🇺🇸New York, New York, United States
Oncology Associates of Oregon, P.C
🇺🇸Eugene, Oregon, United States
Northwest Cancer Specialists, P.C.
🇺🇸Tigard, Oregon, United States
Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale
🇫🇷Paris, France
CHU Bordeaux
🇫🇷Pessac, France
Institut Gustave Roussy; Departement Oncologie Medicale
🇫🇷Villejuif, France
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, Germany
Medical Oncology, Arezzo
🇮🇹Arezzo, Toscana, Italy
Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
🇮🇹Siena, Toscana, Italy
Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department
🇪🇸Barcelona, Spain
Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal
🇪🇸Madrid, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain
Prof. Dr. I. Chiricuta Institute of Oncology
🇷🇴Cluj Napoca, Romania
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Georgetown U; Lombardi Comp Can
🇺🇸Washington, District of Columbia, United States
Barts and the London NHS Trust.
🇬🇧London, United Kingdom
Centrum Med. Ostrobramska NZOZ Magodent
🇵🇱Warszawa, Poland
Medisprof SRL
🇷🇴Cluj-Napoca, Romania