This study will evaluate the efficacy and safety of atezolizumab when given in combination with bevacizumab, investigator's choice of either paclitaxel or pemetrexed, and carboplatin compared with placebo given in combination with bevacizumab, paclitaxel or pemetrexed, and carboplatin in patients with chemotherapy-naive, Stage IV non-squamous Non-Small Cell Lung Cancer (NSCLC). The study will be conducted in two phases: Induction Phase and Maintenance Phase.
Name: Atezolizumab
Name: Placebo
Name: Bevacizumab
Name: Paclitaxel
Name: Pemetrexed
Name: Carboplatin
Description: PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
Measure: Progression Free Survival (PFS) in the intent to treat (ITT) population, as determined by the investigator Time: Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)Description: OS after randomization, defined as the time from randomization to death from any cause.
Measure: Overall Survival (OS) in the ITT population Time: Randomization to death from any cause (up to approximately 33 months)Description: PFS after randomizationdefined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the an Independent Review Facility (IRF) according to RECIST v1.1
Measure: PFS in the ITT population, as determined by IRF Time: Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)Description: PFS after randomization as determined by the investigator according to RECIST v1.1 in the subgroup of patients with PD-L1 expression defined by the SP263 immunohistochemistry (IHC) assay.
Measure: PFS in subgroup of participants with PD-L1 Expression, as determined by the investigator Time: Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)Description: PFS after randomization as determined by the investigator according to RECIST v1.1 in the subgroup of patients with genomic alterations in EGFR (i.e., sensitizing EGFR mutations) or ALK gene.
Measure: PFS in the subgroup of participants with genomic alterations in EGFR or ALK gene, as determined by the investigator Time: Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)Description: ORR, defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1.
Measure: Objective Response Rate (ORR) in the ITT population Time: Randomization until disease progression or death, which ever occurs first (up to approximately 33 months)Description: DOR defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
Measure: Duration of response (DOR) in the ITT population Time: Randomization until the first occurence of a documented objective response to disease progression or death from any cause, whichever occures first (up to approximately 33 months)Description: (TTD) in physical functioning, defined as the time from randomization to the first observed >=10-point decrease in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) for cancer linearly transformed physical functioning scale score that is sustained for two consecutive assessments or followed by death while the patient is on study treatment.
Measure: Time to Deterioration (TTD) in physical functioning in the ITT population Time: Randomization up until approximately 33 monthsAllocation: Randomized
Parallel Assignment
There is one SNP
Patients who have progressed on or were intolerant to first- or second-generation EGFR TKIs, such as erlotinib, gefitinib, afatinib, dacomitinib, and who have no evidence of the EGFR T790M mutation in the tumor tissue after TKI therapy are eligible. --- T790M ---
Patients who have progressed on or were intolerant to first- or second-generation EGFR TKIs and who have evidence of the T790M mutation in their tumor tissue must have also progressed on or were intolerant to osimertinib to be eligible. --- T790M ---