Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer

Eligibility Criteria

• * Life expectancy ≥ 3 months.
• * Pathologically documented NSCLC that meets both of the criteria below:
• * Have documented evidence of Stage IV NSCLC disease at the time of enrollment (based on American Joint Committee on Cancer (AJCC), Eighth Edition).
• * Have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations.
• * Have no actionable genomic alterations such as ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), RET mutations, or other driver oncogenes with approved frontline therapies.
• * Have not received prior systemic treatment for metastatic NSCLC.
• * Measurable disease per RECIST v1.1 criteria by investigator assessment.
• * Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
• * Have adequate organ functions.
• * Have mixed small-cell lung cancer (SCLC) and NSCLC histology.
• * Positive serum pregnancy test or individuals who are breastfeeding or have plans to breastfeed during the study period.
• * Received prior treatment with any anti-PD-1, anti-PD-L1, or any other antibody targeting an immune checkpoint.
• * Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
• * Have an active second malignancy or have had an active second malignancy within 3 years prior to enrollment.
• * Have an active autoimmune disease that required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
• * Are receiving chronic systemic steroids.
• * Have significant third-space fluid retention.
• * Have untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
• * Active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal perforation within 6 months of enrollment.
• * Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• * Has had an allogenic tissue/solid organ transplant.
• * Have received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
• * Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.