This Phase II/III study is evaluating how safe and effective a new targeted therapy (MRTX849) is alone, and in combination with immunotherapy (pembrolizumab), in people with advanced or metastatic non-small cell lung cancer with KRAS G12C mutationA Phase 2 Trial of MRTX849 Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination With Pembrolizumab Versus Pembrolizumab Plus Chemotherapy in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

Inclusion

• Phase 2: Histologically confirmed diagnosis of unresectable or metastatic NSCLC with KRAS G12C mutation and any PD-L1 TPS
• Phase 3: Histologically confirmed diagnosis of unresectable or metastatic squamous or nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS >=50%
• Phase 3: Presence of evaluable or measurable disease per RECIST

• Phase 3: CNS Inclusion - Based on screening brain imaging, patients must have one of the following:

  1. No evidence of brain metastases
  2. Untreated brain metastases not needing immediate local therapy
  3. Previously treated brain metastases not needing immediate local therapy

Exclusion

• Phase 2 and Phase 3: Prior systemic treatment for locally advanced or metastatic NSCLC including chemotherapy, immune checkpoint inhibitor therapy, or a therapy targeting KRAS G12C mutation (e.g., AMG 510).
• Phase 2: Active brain metastases

• Phase 3: Patients with known central nervous system (CNS) lesions must not have any of the following:

  1. Any untreated brain lesions > 1.0 cm in size
  2. Any brainstem lesions
  3. Ongoing use of systemic corticosteroids for control of symptoms of brain lesions at a total daily dose of > 10 mg of prednisone (or equivalent) prior to randomization.
  4. Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain lesions notwithstanding CNS-directed therapy
• Phase 3: Radiation to the lung > 30 Gy within 6 months prior to the first dose of study treatment