Intracranial efficacy of adagrasib in patients with KRAS-G12C mutated NSCLC and untreated CNS metastases

Patients with KRAS-mutated non-small cell lung cancer and untreated CNS metastases have a worse prognosis than similar patients without KRAS mutations. The KRAS^G12C inhibitor adagrasib has demonstrated CNS penetration. The phase 1b cohort of the KRYSTAL-1 trial found intracranial activity of adagrasib in patients with KRAS^G12C-mutated NSCLC and untreated CNS metastases, with intracranial objective response in 42%, disease control in 90%, median progression-free survival of 5.4 months, en median overall survival of 11.4 months. Safety was consistent with previous reports of adagrasib.