Breakthrough Therapy Designation Given to Adagrasib for KRAS G12C–Mutated NSCLC
Posted: Wednesday, July 7, 2021
The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy designation to the oral small-molecule KRAS G12C inhibitor adagrasib for treatment of patients with non–small cell lung cancer (NSCLC) with KRAS G12C mutations following prior systemic therapy.
The FDA’s decision was based on preliminary findings from the multicohort phase I/II KRYSTAL-01 clinical trial. The study enrolled patients with advanced or metastatic solid tumors that harbor a KRAS G12C mutation and who received prior treatment with chemotherapy and anti–PD-1/PD-L1 therapy. In phase I, participants received a twice-daily 600-mg dose of adagrasib. In phase II, adagrasib monotherapy was assessed in patients with NSCLC, colorectal cancer, and other solid tumors.
As of August 30, 2020, 79 patients with pretreated NSCLC received adagrasib. Updated data from the trial were presented during the 2021 European Lung Cancer Virtual Congress. The clinical benefit rate with adagrasib in the phase I/Ib portion of the trial was 96%, and the overall response rate was 43%. The overall response rate in the phase II cohort was 45%. After a median follow-up of 9.6 months, the investigators reported that five of six patients who responded to treatment continued use of adagrasib. Of these patients, four had an ongoing response to treatment for more than 11 months. The median time to response was 1.5 months, and the median duration of treatment was 8.2 months.
The most frequent all-grade treatment-related adverse effects for patients who received adagrasib were nausea, diarrhea, vomiting, and fatigue. Grade 3 or 4 treatment-related adverse events included fatigue, increased alanine aminotransferase, aspartate aminotransferase, and QT prolongation. Grade 5 adverse events included pneumonitis and cardiac failure.