A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer)

This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in patients with metastatic non-small cell lung cancer (NSCLC). Two cohorts will be enrolled in parallel in this study: the first-line (1L) cohort will consist of patients who have not received any systemic therapy for their disease and the second-line (2L) cohort will consist of patients who progressed during or after receiving a platinum-containing regimen and a PD-L1 / PD-1 checkpoint inhibitor treatment. In each cohort, eligible patients will be assigned to one of several treatment arms.

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
• Availability of peripheral blood for next-generation sequencing (NGS) circulating tumor deoxyribonucleic acid (ctDNA) testing.
• 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) >= 50% 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
• Current treatment with anti-viral therapy for hepatitis B virus (HBV)
• 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

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Hoffmann-La Roche

• Primary ID BO39610
• Secondary IDs NCI-2018-00183, 2017-001267-21
• Clinicaltrials.gov ID NCT03337698