A Study of Atezolizumab in Combination With Carboplatin Plus (+) Paclitaxel With or Without Bevacizumab Compared With Carboplatin+Paclitaxel+Bevacizumab in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population

Time frame: Baseline until death (up approximately 53 months)

Population: ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population

Time frame: Baseline until death until data cut-off on 22 January 2018 (up to approximately 34 months)

Population: ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Progression Free Survival (PFS), as Determined by the Investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.

Time frame: Baseline until disease progression or death, whichever occurs first until data cut-off on 15 September 2017 (up to approximately 29 months)

Population: Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

The SILC (Symptoms in Lung Cancer) scale was used to assess patient-reported severity of lung cancer symptoms (chest pain, dyspnea, and cough). The SILC scale is a 9-item content validated self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a symptom severity score. The SILC questionnaire comprises three individual symptoms (dyspnea, cough, chest pain) and are scored at the individual symptom level, thus have a dyspnea score, chest pain score, and cough score. Each individual symptom score is calculated as the average of responses for the symptom items \[e.g. Chest Pain Score=mean (item 1; item 2)\]. An increase in score is suggestive of a worsening in symptomology (i.e. frequency or severity). A score change of ≥0.3 points for the dyspnea and cough symptom scores is considered to be clinically significant; whereas a score change of ≥0.5 points for the chest pain score is considered to be clinically significant.

Time frame: Baseline up to approximately 29 months

Population: No participants were analyzed due to psychometric properties within the NSCLC population are still being determined. Due to quality issues data not analyzed.

Time frame: Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length=21 days)

Population: The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 21 (Cycle length=21 days)

Population: The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

DOR, as determined by investigator according to RECIST v1.1 in Arm B versus Arm C in the Teff high-WT population and the ITT-WT population.

Time frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Population: Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes.

Time frame: Day 1 of Cycle 1 and 3 (Cycle length=21 days)

Population: The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

Time frame: Day 21 of Cycles 1, 2 3, and 7 (Cycle length=21 days)

Population: The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

Time frame: Baseline until death (up approximately 53 months)

Population: Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

OS in Arm A Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)

Time frame: Baseline until death (up approximately 53 months)

Population: PD-L1 WT populations are defined as the PD-L1 populations (TC2/3 or IC2/3 population or TC1/2/3 or IC1/2/3 population) excluding patients with an activating EGFR mutation or ALK translocation.

Time frame: Baseline until death (up approximately 53 months)

Population: Teff-high WT population, defined as Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. Teff-high population, defined as patients in the ITT population with Teff signature expression \>=-1.91. ITT population is defined as all randomized patients, regardless of receipt of the assigned treatment.

OS in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)

Time frame: Baseline until death (up to approximately 34 months)

Population: The PD-L1-selected WT populations are defined as the PD-L1-selected populations (TC2/3 or IC2/3 population or TC1/2/3 or IC1/2/3 population) excluding patients with a sensitizing EGFR mutation or ALK translocation.

Time frame: Baseline until death (up to approximately 34 months)

Population: Teff-high WT population, defined as the Teff-high population excluding patients with activating EGFR mutation or ALK translocation. Teff-high population, defined as participants in the ITT population with Teff signature expression \>=-1.91. ITT population, defined as all randomized patients, regardless of receipt of the assigned treatment.

OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.

Time frame: Baseline to 2 years or death, whichever occurs first.

Population: Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.

Time frame: Baseline to 2 years or death, whichever occurs first.

Population: Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Percentage of participants with at least one adverse event.

Time frame: Baseline up to data cutoff date 7 December 2020 (up to approximately 68 months)

Population: Safety population included all treated patients, defined as randomized patients who received any amount of any component of study treatment.

Percentage of Participants With an Objective Response (OR) (Complete Response \[CR\] or Partial Response \[PR\]) as Determined by the Investigator using RECIST v1.1 in the Teff-High-WT population and ITT-WT population.

Time frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Population: Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Time frame: Baseline up to approximately 29 months

Population: The baseline ADA-evaluable population for each study treatment included patients who had a baseline ADA result. The post-baseline ADA-evaluable population for each study treatment included patients who had at least one post-baseline ADA result and had received at least on dose of that study treatment.

PFS, as determined by the independent review facility (IRF) Using RECIST v1.1 in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.

Time frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Population: Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

PFS, as determined by the investigator according to RECIST v1.1, in Arm A versus B in the Teff high-WT population and ITT-WT population.

Time frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Population: Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

PFS as Determined by the Investigator according to RECIST v1.1, in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)

Time frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Population: The PD-L1-selected WT populations are defined as the PD-L1-selected populations (TC2/3 or IC2/3 population or TC1/2/3 or IC1/2/3 population) excluding patients with a sensitizing EGFR mutation or ALK translocation.

PFS, as determined by the investigator according to RECIST v1.1, in Arm B versus C in the Teff high population and ITT population.

Time frame: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Population: Teff-high population is defined as the patients in the ITT population with Teff signature expression \>=-1.91. ITT population is defined as all randomized patients, regardless of receipt of the assigned treatment.

Time frame: Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 h after carboplatin infusion (infusion duration=15 to 30 minutes) on D1 of Cy1,3 (Cycle length=21 days)

Population: The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

Time frame: Predose (same day of treatment administration), 5-10 minutes before end of paclitaxel infusion, 1 h after paclitaxel infusion (infusion duration=3 h) on D1 of Cy1,3 (Cycle length=21 days)

Population: The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

EORTC QLQ-C30 is a validated & reliable self-report measure (Aaronson et al.1993;Fitzsimmons et al.1999) that consists of 30 questions that assess 5 aspects of patient functioning (physical,emotional,role, cognitive,and social), 3 symptom scales (fatigue,nausea & vomiting, pain),global health/quality of life,and six single items (dyspnea,insomnia, appetite loss,constipation,diarrhea, and financial difficulties). EORTC QLQ-C30 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life);however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al.1998).

Time frame: Baseline up to approximately 29 months

Population: Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

QLQ-LC13 Quality-of-Life Questionnaire Lung Cancer Module incorporates one multiple-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998).

Time frame: Baseline up to approximately 29 months

Population: Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.