A Phase 1b Study of Atezolizumab in Combination With Erlotinib or Alectinib in Participants With Non-Small Cell Lung Cancer (NSCLC)

Inclusion criteria

• Histologically or cytologically documented, locally advanced or metastatic NSCLC.
• Participants in Stage 1 (Safety Evaluation) receiving erlotinib: No limit to the number of prior therapies (except for EGFR TKIs).
• Participants in Stage 2 (Expansion) receiving erlotinib: i) sensitizing mutation in the EGFR gene and ii) consent to collection of tumor tissue samples before, during, and after treatment for biopsy and PD biomarker analyses.
• Participants receiving alectinib in either Stage 1 or Stage 2: must be ALK positive as assessed by Food and Drug Administration (FDA) approved test and must not have received prior treatment for their advanced NSCLC.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 12 weeks.
• Measurable disease, as defined by RECIST Version 1.1 (v1.1).
• Adequate hematologic and end-organ function.
• Use of highly effective contraception (as defined by protocol) and until 5 months after the last dose of atezolizumab and for 3 months after the last dose of alectinib or for 2 weeks after the last dose of erlotinib, whichever is longer; Males must also refrain from sperm donatation during this same time period. Participants must not be pregnant or breastfeeding.
• Archival tumor tissue specimen meeting protocol specifications or the participant will be offered the option of a pre-treatment biopsy to obtain adequate tissue sample.

Exclusion criteria

• For participants receiving erlotinib group: prior treatment with any EGFR mutant-targeting TKI
• Any approved anticancer therapy, including chemotherapy, or hormonal therapy (except hormone-replacement therapy or oral contraceptives) within 3 weeks of first dose.
• Treatment with any other test drug or participation in another clinical trial within 28 days of enrollment.
• Known symptomatic central nervous system (CNS) metastases. Participants with a history of treated or untreated asymptomatic CNS metastases may be eligible.
• Leptomeningeal disease.
• Uncontrolled tumor-related pain.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage at least once monthly.
• High levels of calcium requiring bisphosphonate therapy or denosumab.
• Malignancies other than NSCLC within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (such as adequately treated carcinoma in-situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ).
• History of severe allergic, anaphylactic, or other 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.
• History of autoimmune disease.
• Participants with prior bone marrow or solid organ transplantation.
• History of lung inflammation or disease.
• Serum albumin less than (<) 2.5 grams per deciliter (g/dL).
• Positive for Human Immunodeficiency Virus (HIV).
• Liver disease.
• Current or active tuberculosis, hepatitis B, or hepatitis C.
• Participants with past or resolved hepatitis B virus (HBV) infection are eligible; participants positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV Riboxy Nucleic Acid (RNA).
• Signs or symptoms of infection within 2 weeks prior to first dosing.
• Received therapeutic oral or IV antibiotics within 2 weeks prior to first dosing.
• Significant cardiovascular disease.
• Major surgical procedure other than for diagnosis within 28 days prior to first dosing or during the course of the study.
• Administration of a live, attenuated vaccine within 4 weeks before first dosing or during the study.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that may reasonably prevent the participant from participating.
• Hypersensitivity to erlotinib or alectinib or to any of the excipients.
• Any significant ophthalmologic abnormality. The use of contact lenses is not recommended during the study.
• For participants receiving alectinib: baseline Fridericias corrected QT interval (QTcF) greater than (>) 470 milliseconds (ms) or symptomatic bradycardia.
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies.
• Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of the drug, whichever is shorter, prior to first dosing.
• Treatment with systemic immunosuppressive medications within 2 weeks prior to first dosing (inhaled corticosteroids and mineralocorticoids are allowed).
• Participants who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication are elgible for study after discussion and approval by the Medical Monitor.