Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS G12C Mutation KRYSTAL-7

Inclusion Criteria:

* 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 measurable disease per RECIST1.1
* 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 Criteria:

* 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 \> 2.0 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