Dr. Gadgeel on CNS Activity Achieved With Adagrasib in KRAS G12C+ NSCLC

Shirish M. Gadgeel, MD, head, the Division of Hematology/Oncology, associate director, Patient Experience and Clinical Care, the Henry Ford Cancer Institute, discusses the efficacy of adagrasib in patients with KRAS G12C–mutated non–small cell lung cancer (NSCLC) and central nervous system (CNS) metastases.

The phase 1/2 KRYSTAL-1 trial (NCT03785249) examined the use of adagrasib in patients with advanced solid tumors, including NSCLC, whose tumors harbored KRAS G12C mutations.

The phase 1b cohort included 19 patients who had KRAS G12C–mutant NSCLC and CNS metastases that had not been previously treated with local approaches such as radiation or surgery, Gadgeel says. Data presented during the 2022 ASCO Annual Meeting showed that in this patient population, adagrasib produced an intracranial overall response rate (ORR) of 32%; the median intracranial duration of response (DOR) was not yet reached, Gadgeel adds.

Cohort A of the phase 2 portion of the trial included 33 patients with treated, stable CNS metastases. In this population, the intracranial ORR achieved with adagrasib was 33%, and the median intracranial DOR was 11.2 months. In the full cohort of patients with previously treated KRAS G12C–mutated disease (n = 112), the ORR with adagrasib was 43%.

Because adagrasib demonstrated activity both inside and outside of the CNS, the drug has a clear advantage, Gadgeel concludes.