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

Prior treatment

• Received prior treatment with any anti-PD-1, anti-PD-L1, or any other antibody targeting an immune checkpoint.
• Have an active second malignancy or have had an active second malignancy within 3 years prior to enrollment.
• Are receiving chronic systemic steroids.
• 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.

Other illness

• Have mixed small-cell lung cancer (SCLC) and NSCLC histology.
• Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
• 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).
• 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.
• Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Lab values

• Positive serum pregnancy test or individuals who are breastfeeding or have plans to breastfeed during the study period.

Other

• Have significant third-space fluid retention.
• Have untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.

• 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.