Randomized, Double-Blind

Adagrasib plus Pembrolizumab plus Chemotherapy vs. Placebo plus Pembrolizumab plus Chemotherapy

• PFS
• OS

• Measurable disease via computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria of at least 1 lesion.
• Participants with brain metastases are eligible for enrollment, including those with untreated brain metastases. Brain metastases must be asymptomatic and not in need of immediate local therapy. Any untreated brain metastases must be ≤ 20 mm in diameter.
• No evidence of leptomeningeal metastases (carcinomatous meningitis) or brainstem lesions.

• History of previous cancer requiring therapy within the previous 2 years, except for squamous cell or basal-cell carcinoma of the skin or any in situ carcinoma that has been completely resected.
• Radiation to the lung > 30 Gy within 6 months prior to the first dose of study treatment.
• Participants with an active, known, prior documented, or suspected autoimmune or inflammatory disease, including:
  i) Inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis);
  ii) History of interstitial lung disease (ILD) or radiation pneumonitis requiring active steroid treatment, or any evidence of clinically active ILD or pneumonitis;
  iii) Other medically active autoimmune disease within 2 years prior to the first dose of study treatment. Note: Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment, including, but not limited to, any of the following:
  i) Myocardial infarction, unstable angina, coronary/peripheral artery bypass graft surgery, symptomatic peripheral vascular disease (ie, CTCAE v5.0 peripheral ischemia of any grade), class III or IV congestive heart failure (as defined by the New York Heart Association; refer to APPENDIX 8), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, pericarditis, or myocarditis;
  ii) Ongoing clinically significant symptomatic cardiac dysrhythmias, history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes), prolonged QTc interval (> 480 milliseconds) or family or medical history of congenital long QT syndrome.