This Phase III, global, multicenter, open-label, randomized, controlled study will evaluate the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 [anti-PD-L1] antibody) compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy due to poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status of 2-3).
Name: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Description: Atezolizumab will be administered via IV infusion once every three weeks (QW3).Type: DrugAtezolizumab
Name: Vinorelbine
Description: Vinorelbine will be administered per relevant local guidelines and Summary of Product Characteristics (SmPC) management.Type: DrugSingle Agent Chemotherapy (Vinorelbine or Gemcitabine)
Name: Gemcitabine
Description: Gemcitabine will be administered per relevant local guidelines and SmPC management.Type: DrugSingle Agent Chemotherapy (Vinorelbine or Gemcitabine)
Description: Objective response is defined as partial response (PR) plus complete response (CR).
Measure: Percentage of Participants With Objective Response, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (v1.1) Time: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years)Allocation: Randomized
Parallel Assignment
There is one SNP
Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the American Joint Committee on Cancer (AJCC) 7th edition - No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19 deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected - No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition - Life expectancy greater than or equal to (>/=) 8 weeks - Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to poor performance status (ECOG performance status of 2-3). --- L858R ---
Grade 3 or higher toxicities due to any prior therapy (example [e.g.], radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication - Participants who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy General Medical Exclusion Criteria: - History of autoimmune disease except autoimmune-related hypothyroidism and controlled Type I diabetes mellitus - History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis - Known positivity for human immunodeficiency virus (HIV) - Known active hepatitis B or hepatitis C - Active tuberculosis - Severe infections within 4 weeks prior to randomization - Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina - Major surgical procedure other than for diagnosis within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study - Prior allogeneic bone marrow transplantation or solid organ transplant - Participants with an illness or condition that may interfere with capacity or compliance with the study protocol, as per investigator's judgment - Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to randomization Exclusion Criteria Related to Atezolizumab: - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation - Oral or IV antibiotic treatment - Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study - Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies - Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to randomization - Treatment with systemic corticosteroids or other immunosuppressive medications - Participants not willing to stop treatment with traditional herbal medicines Exclusion Criteria Related to Chemotherapy: - Known sensitivity and contraindications to the 2 comparative chemotherapy agents (that is [i.e.] vinorelbine, oral or intravenous, and gemcitabine, intravenous) Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the American Joint Committee on Cancer (AJCC) 7th edition - No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19 deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected - No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition - Life expectancy greater than or equal to (>/=) 8 weeks - Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to poor performance status (ECOG performance status of 2-3). --- L858R ---