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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
305
Atezolizumab will be administered by IV infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Placebo matching to atezolizumab will be administered by IV infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.
Paclitaxel will be administered by IV infusion at a dose of 175 mg/m2.
Pemetrexed will be administered by IV infusion at a dose of 500 mg/m2.
Carboplatin will be administered by IV infusion to achieve an initial target AUC of 6 mg/mL/min.
Peking Union Medical College Hospital
Beijing, China
Beijing Cancer Hospital
Beijing, China
Beijing Chest Hospital; Oncology Department
Beijing, China
the First Hospital of Jilin University
Changchun, China
Jilin Cancer Hospital
Changchun, China
West China Hospital, Sichuan University
Chengdu, China
The 900th Hospital of PLA joint service support force
Fuzhou, China
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, China
Sir Run Run Shaw Hospital
Hangzhou, China
Harbin Medical University Cancer Hospital
Harbin, China
...and 13 more locations
Progression Free Survival (PFS) in the intent to treat (ITT) population, as determined by the investigator
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
Time frame: Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)
Overall Survival (OS) in the ITT population
OS after randomization, defined as the time from randomization to death from any cause.
Time frame: Randomization to death from any cause (up to approximately 33 months)
PFS in the ITT population, as determined by IRF
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
Time frame: Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)
PFS in subgroup of participants with PD-L1 Expression, as determined by the investigator
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.
Time frame: Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)
PFS in the subgroup of participants with genomic alterations in EGFR or ALK gene, as determined by the investigator
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.
Time frame: Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months)
Objective Response Rate (ORR) in the ITT population
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.
Time frame: Randomization until disease progression or death, which ever occurs first (up to approximately 33 months)
Duration of response (DOR) in the ITT population
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.
Time frame: 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)
Time to Confirmed Deterioration (TTCD) in physical functioning in the ITT population
(TTCD) 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 an initial clinically meaningful decrease above baseline followed by death within three weeks.
Time frame: Randomization up until approximately 33 months
Percentage of Participants With Adverse Events
Time frame: Randomization up to approximately 33 months
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