A Study to Evaluate Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients with Metastatic Non-Small Cell Lung Cancer (Morpheus-Lung)

INTERVENTION: Product Name: Atezolizumab Product Code: RO5541267 Pharmaceutical Form: Solution for infusion INN or Proposed INN: ATEZOLIZUMAB Current Sponsor code: RO5541267/F03 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 60‐ Product Name: Cobimetinib (GDC‐0973) Product Code: RO5514041/F04 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Cobimetinib CAS Number: 934660‐93‐2 Current Sponsor code: RO5514041/F04 Other descriptive name: COBIMETINIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Product Name: Cobimetinib (GDC‐0973) Product Code: RO5514041/F09 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Cobimetinib CAS Number: 934660‐93‐ Current Sponsor code: RO5514041/F09 Other descriptive name: COBIMETINIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Product Name: CEA‐TCB Product Code: RO6958688 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: CEA‐TCB CAS Number: NA Current Sponsor code: RO6958688/F03 Other descriptive name: CEA‐TCB Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 20‐ Product Name: BL‐8040 Product Code: RO7200024 Pharmaceutical Form: Lyophilisate for solution for injection INN or Proposed INN: BL‐8040 Current Sponsor code: RO7200024 Other descriptive name: BL‐8040 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 73‐ Product Name: Tazemetostat Product Code: RO7116575 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: TAZEMETOSTAT CAS Number: 1467052‐75‐0 Current Sponsor code: RO7116575 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Product Name: CPI‐444 Product Code: RO7235239 Pharmaceutical Form: Capsule INN or Proposed INN: NA CAS Number: 1202402‐40‐1 Current Sponsor code: RO7235239 Other descriptive name: V81444, BIIB034, VER‐81444 CONDITION: Non‐small cell lung cancer (NSCLC) ; MedDRA version: 20.0 Level: PT Classification code 10029522 Term: Non‐small cell lung cancer stage IV System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: Stage 1:; To evaluate the efficacy of immunotherapy‐based treatment combinations based on objective response Primary end point(s): 1. Objective response rate Secondary Objective: Stage 1:; To evaluate the efficacy of immunotherapy‐based treatment combinations based on progression free survival (PFS), overall survival (OS) after randomization and at specific time points, duration of response (DOR) and disease control; ; Stage 1 and 2:; •To evaluate the safety of immunotherapy‐based treatment combinations; •To characterize the pharmacokinetic profile of drugs that are administered as part of an immunotherapy‐based treatment combinations; •To evaluate the immune response to drugs that are administered as part of an immunotherapy‐based treatment combinations Timepoint(s) of evaluation of this end point: 1. Complete response or partial response on two consecutive occasions SECONDARY OUTCOME: Secondary end point(s): Stage 1; 1. PFS; 2. OS; 3. DOR; 4. Disease control rate; 5. OS at specific time points; Stage 1 and 2; 6. Incidence, nature, and severity of adverse events and laboratory abnormalities, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 ; 7. Change from baseline in vital signs, electrocardiogram parameters and targeted clinical laboratory test results; 8. Plasma or serum concentration of each drug at specified timepoints; 9. For drugs for which anti‐drug antibody (ADA) formation is measured: presence of ADAs during the study relative to the presence of ADAs at baseline Timepoint(s) of evaluation of this end point: Stage 1; 1‐5. As defined in the study protocol; Stage 1 and 2; 6‐9. As defined in the study protocol INCLUSION CRITERIA: ‐ Age >= 18 years ‐ Eastern Cooperative Oncology Group Performance Status of 0 or 1 ‐ Life expectancy >= 3 months ‐ Histologically or cytologically confirmed metastatic, non‐squamous or squamous NSCLC ‐ For patients in Cohort 1: no prior systemic therapy for metastatic NSCLC ‐ For patients in Cohort 2: disease progression during or following treatment for metastatic NSCLC that consisted of a platinum‐containing regimen and a Programmed death‐ligand 1(PD‐L1)/PD‐1 checkpoint inhibitor, given in combo as one line of therapy or as two separate lines of therapy for a maximum of two prior lines of systemic therapy ‐ Availability of a representative tumor specimen that is suitable for determination of PD‐L1 and/or additional biomarker status by means of central testing ‐ For patients in Cohort 1: High tumor PD‐L1 expression Stage 1 and 2 ‐ Measurable disease according to Response Evaluation Criteria in Solid Tumors, Version 1.1 ‐ Adequate