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 withKRAS G12C mutation and any PD-L1 TPS

• Phase 3: Histologically confirmed diagnosis of unresectable or metastatic squamousor 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 ofthe 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 metastaticNSCLC including chemotherapy, immune checkpoint inhibitor therapy, or a therapytargeting 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 anyof 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 brainlesions at a total daily dose of > 10 mg of prednisone (or equivalent) prior torandomization.

4. Have poorly controlled (> 1/week) generalized or complex partial seizures, ormanifest neurologic progression due to brain lesions notwithstandingCNS-directed therapy

• Phase 3: Radiation to the lung > 30 Gy within 6 months prior to the first dose ofstudy treatment