Overview
This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (NSCLC).
Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of participants with tumor PD-L1 expression who have received no prior systemic therapy for metastatic NSCLC, and Cohort 2 will consist of participants who experienced disease progression during or following treatment with a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor, given in combination as one line of therapy or as two separate lines of therapy, regardless of PD-L1 expression. In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). Participants who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen (Stage 2).
Eligibility
General Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) performance Status of 0 or 1
- Life expectancy greater than or equal to 3 months
- Histologically or cytologically confirmed metastatic, non-squamous or squamous Non-Small Cell Lung Cancer (NSCLC)
- Measurable disease (at least one target lesion)
- Adequate hematologic and end-organ function
- Tumor accessible for biopsy
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating eggs as outlined for each specific treatment arm
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
Inclusion Criteria for Cohort 1
- No prior systemic therapy for metastatic NSCLC
- High tumor PD-L1 expression, defined as Tumor Proportion Score (TPS) or TCs >= 50% or TC3
Inclusion Criteria for Cohort 2
- Disease progression during or following treatment for metastatic or locally advanced, inoperable NSCLC
Exclusion Criteria
- Prior allogeneic stem cell or solid organ transplantation
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- History of leptomeningeal disease
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
- History of malignancy other than NSCLC within 2 years prior to screening
- Active tuberculosis
- Severe infection within 4 weeks prior to initiation of study treatment