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

Prior treatment

• 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 3: Patients with known central nervous system (CNS) lesions must not have any of the following:
  • Any untreated brain lesions \> 2.0 cm in size
  • Any brainstem lesions
  • 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.
  • 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

Other

• Phase 2: Active brain metastases

• 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:
  • No evidence of brain metastases
  • Untreated brain metastases not needing immediate local therapy
  • Previously treated brain metastases not needing immediate local therapy