Dr. Spira on the FDA Approval of Adagrasib in KRAS G12C–mutant NSCLC

Alexander I. Spira, MD, PhD, FACP, co-director, Virginia Cancer Specialists Research Institute; director, Thoracic and Phase I Program, clinical assistant professor, Johns Hopkins School of Medicine, discusses the FDA approval of adagrasib (MRTX 849) in patients with KRAS G12C–mutated non–small cell lung cancer (NSCLC).

On December 12, 2022, the FDA granted accelerated approval to adagrasib for use in adult patients with NSCLC harboring KRAS G12C mutations. The regulatory decision was based on findings from the phase 2 KRYSTAL-1 trial (NCT03785249), in which the agent elicited an objective response rate of 43% and a disease control rate of 80%.

Adagrasib joins sotorasib (Lumakras) as another KRAS G12C inhibitor in NSCLC, Spira says. Although the agents are similar to each other, they have different adverse effect profiles, according to Spira. Moreover, compelling data suggest that adagrasib has central nervous system (CNS) penetration, which may make it unique from sotorasib, for which CNS penetration has yet to be defined, Spira explains.

This approval opens an additional treatment option for patients with KRAS G12C–mutant NSCLC, and providers can choose between adagrasib and sotorasib based on their toxicity profiles, Spira concludes.