The Food and Drug Administration (FDA) has accepted the New Drug Application for adagrasib for the treatment of patients with non-small cell lung cancer (NSCLC) harboring the KRASG12C mutation who have received at least 1 prior systemic therapy.
Adagrasib is an investigational, highly selective, potent oral small molecule inhibitor of KRASG12C designed to sustain target inhibition by irreversibly locking the mutant protein in its inactive state. The application is supported by data from the registration-enabling cohort of the phase 2 KRYSTAL-1 study (ClinicalTrials.gov Identifier: NCT03785249), which evaluated adagrasib in adults with NSCLC harboring the KRASG12C mutation following prior systemic therapy. Patients received adagrasib 600mg orally twice a day.
After a median follow-up of 9 months, results showed an objective response rate (ORR) of 43% and a disease control rate of 80% in the intent-to-treat population, based on central independent review as of June 15, 2021. Moreover, 98.3% of patients received adagrasib after treatment with immunotherapy and chemotherapy. The safety and tolerability profile of adagrasib was consistent with previously reported findings on its use in patients with advanced NSCLC.
“KRAS mutations have been notoriously hard to target and historically have had limited therapeutic options. The KRASG12C biomarker in particular is associated with poor survival outcomes,” said Pasi A. Jänne, MD, PhD, an investigator participating in the KRYSTAL-1 study, and director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute. “The FDA’s review of the adagrasib NDA marks important progress toward potentially providing a new, targeted option for those living with KRASG12C mutated non-small cell lung cancer.”
A Prescription Drug User Fee Action (PDUFA) target date of December 14, 2022 has been set for the application. The NDA is being reviewed by the FDA for accelerated approval.
The Company is currently evaluating the efficacy of adagrasib vs docetaxel in patients with the KRASG12C mutation who have been previously treated for metastatic NSCLC in a confirmatory phase 3 trial (KRYSTAL-12; ClinicalTrials.gov Identifier: NCT04685135).
- U.S. Food and Drug Administration (FDA) accepts Mirati Therapeutics’ New Drug Application for adagrasib as treatment of previously treated KRASG12C–mutated non-small cell lung cancer. News release. Mirati Therapeutics, Inc. February 15, 2022. Accessed February 16, 2022. https://www.prnewswire.com/news-releases/us-food-and-drug-administration-fda-accepts-mirati-therapeutics-new-drug-application-for-adagrasib-as-treatment-of-previously-treated-krasg12c-mutated-non-small-cell-lung-cancer-301483014.html.
- Mirati Therapeutics announces positive phase 2 topline results for investigational adagrasib in patients with KRASG12C-mutated advanced non-small cell lung cancer. News release. Mirati Therapeutics, Inc. September 20, 2021. Accessed February 16, 2022. https://ir.mirati.com/press-releases/press-release-details/2021/Mirati-Therapeutics-Announces-Positive-Phase-2-Topline-Results-for-Investigational-Adagrasib-in-Patients-with-KRAS-G12C-Mutated-Advanced-Non-Small-Cell-Lung-Cancer/default.aspx.