This is a Phase III, multicenter, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of atezolizumab versus placebo in participants with RCC who are at high risk of disease recurrence following nephrectomy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
778
Atezolizumab 1200 mg IV infusion q3w
Placebo matching to atezolizumab q3w
Investigator-assessed Disease-Free Survival (DFS)
Investigator-assessed DFS, defined as the time from randomization to death from any cause or the first documented recurrence assessed by investigator, whichever occurred first. Recurrence was defined as any of the following: Local recurrence of renal cell carcinoma (RCC), new primary RCC, or distant metastasis of RCC. Investigator-assessed DFS was analyzed similarly to the analysis of IRF-assessed DFS.
Time frame: From baseline up to first occurence of event by investigator assessment (up to approximately 64 months)
Overall Survival (OS)
OS was defined as the time from randomization to death from any cause.
Time frame: From baseline up to death due to any cause (up to approximately 64 months)
Investigator-assessed DFS in Participants With Tumor-Infiltrating Immune Cell (IC) 1/2/3
Investigator assessed DFS for participants with PD-L1 expression of IC1/2/3 vs IC0, defined as the time from randomization to death from any cause or the first documented recurrence assessed by investigator, whichever occurred first. Investigator-assessed DFS was analyzed similarly to the analysis of IRF-assessed DFS. PD-L1 IC0 was defined as \<1% and IC1/2/3 was defined as \>=1% of tumor-infiltrating IC expressing PD-L1 as assessed by immunohistochemistry using SP142 assay. Recurrence was defined as any of the following: Local recurrence of renal cell carcinoma (RCC), new primary RCC, or distant metastasis of RCC.
Time frame: From baseline until first occurrence of DFS event (up to approximately 64 months)
Independent Review Facility (IRF)-Assessed DFS
IRF-assessed DFS was defined as the time from randomization to death from any cause or the first documented recurrence assessed by IRF, whichever occurred first.
Time frame: From baseline until first documented recurrence event (up to approximately 64 months)
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IRF-assessed DFS in Participants With Tumor-Infiltrating IC 1/2/3
IRF-assessed DFS was defined as the time from randomization to death from any cause or the first documented recurrence assessed by IRF, whichever occurred first. PD-L1 IC0 was defined as \<1% and IC1/2/3 was defined as \>=1% of tumor-infiltrating IC expressing PD-L1 as assessed by immunohistochemistry using SP142 assay.
Time frame: From baseline until first occurrence of DFS event (up to approximately 64 months)
IRF-assessed Event-free Survival (EFS)
IRF-assessed EFS was defined as the time from randomization to death from any cause, or the first documented recurrence in participants without baseline disease by IRF or the first documented disease progression in participants identified as having baseline disease by IRF, whichever occurred first. Disease progression was defined as either unequivocal progression of baseline disease or new unequivocal lesions.
Time frame: From baseline until first documented recurrence event (up to approximately 64 months)
Disease-Specific Survival
Disease-specific survival was defined as the time from randomization to death from renal cell carcinoma (RCC).
Time frame: From baseline up to death due to RCC (up to approximately 64 months)
Distant Metastasis-Free Survival
Distant metastasis-free survival, defined as the time from randomization to death from any cause or the date of diagnosis of distant (i.e., non-locoregional) metastases assessed by the investigator, whichever occurred first.
Time frame: From baseline up to date of diagnosis of distant metastases or death due to any cause (up to approximately 64 months)
Percentage of Participants Who Are Alive and IRF-assessed Recurrence Free at Year 1, 2, and 3
IRF-assessed DFS was defined as the percentage of participants being alive and free of recurrence assessed by IRF at Year 1, 2, and 3 after randomization.
Time frame: Up to 3 years
Percentage of Participants Who Are Alive and Investigator-assessed Recurrence Free at Year 1, 2, and 3
Investigator-assessed DFS rate was defined as the percentage of participants being alive and free of recurrence assessed by investigator at Year 1, 2, and 3 after randomization.
Time frame: Up to 3 years
Percentage of Participants With Adverse Events
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unitended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a pharmaceutical product whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as a AEs.
Time frame: From baseline up to death due to any cause (up to approximately 71 months)
Maximum Serum Concentration (Cmax) of Atezolizumab
Time frame: Predose (Hour[hr]0), 0.5 hr after end of infusion (infusion duration=1 hr) on Cycle 1 Day 1; predose (hr 0) on Day 1 of Cycles 2, 3, 4, 8; at treatment discontinuation (up to 1 year); 90-120 days after last dose (last dose = up to 1 year) (Cycle=21 days)
Minimum Serum Concentration (Cmin) of Atezolizumab
Time frame: Predose (Hour[hr]0), 0.5 hr after end of infusion (infusion duration=1 hr) on Cycle 1 Day 1; predose (hr 0) on Day 1 of Cycles 2, 3, 4, 8; at treatment discontinuation (up to 1 year); 90-120 days after last dose (last dose = up to 1 year) (Cycle=21 days)
Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab
Time frame: Predose (hr 0) on Day 1 of Cycles 1, 2, 3, 4, 8; at treatment discontinuation (up to 1 year); 90-120 days after last dose (last dose = up to 1 year) (Cycle=21 days)