New Drug Application for Adagrasib Accepted by FDA for KRAS G12C+ NSCLC

A new drug application for adagrasib was accepted by the FDA for the treatment of patients with KRAS G12C–mutated non–small cell lung cancer.

The FDA has accepted a new drug application (NDA) for adagrasib (MRTX 849) as treatment for patients with previously treated KRAS G12C–positive non–small cell lung cancer (NSCLC), according to a press release from drug developer Mirati Therapeutics.1

Adagrasib is being assessed by the FDA for accelerated approval, which is designated for drugs capable of treating serious conditions and for fulfilling unmet medical needs based on a surrogate end point. The application is also being reviewed under the FDA Real-Time Oncology Review pilot program, which could result in a more efficient review process that would allow more safe and effective treatments to be made more readily available.

Adagrasib has a prescription drug action date of December 14, 2022.

KRAS mutations have been notoriously hard to target and historically have had limited therapeutic options. The KRAS G12C biomarker in particular is associated with poor survival outcomes. The FDA's review of the adagrasib NDA marks important progress toward potentially providing a new, targeted option for those living with KRAS G12C-mutated [NSCLC],” investigator Pasi A. Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, said in a press release.

Adagrasib most recently earned a breakthrough therapy designation from the FDA for patients with KRAS G12C–mutant NSCLC in June 2021 based on findings from the phase 2 KRYSTAL-1 trial (NCT03785249).2 Patients in the intent-to-treat arm who received a 600 mg dose of adagrasib twice daily experienced an overall response rate of 43% and a disease control rate of 80% by central independent review.3 The study had a median follow-up of 9.0 months.

The ongoing, confirmatory phase 3 KRYSTAL-12 trial is evaluating the use of second-line adagrasib compared with docetaxel in patients with KRAS G12C–mutated NSCLC.

“The acceptance of our NDA for adagrasib is a significant step forward in Mirati's ongoing efforts to advance innovative, differentiated treatment options for patients with KRAS G12C cancers,” Charles Baum, MD, PhD, president, founder, and head of research and development at Mirati Therapeutics, Inc, concluded. “We look forward to working with the FDA during their review of our application and potentially provide a novel option for patients with [NSCLC].”

Results from the KRYSTAL-1 study will be presented at an upcoming medical conference in the first half of 2022.


  1. U.S. Food and Drug Administration (FDA) accepts Mirati Therapeutics' new drug application for adagrasib as treatment of previously treated KRAS G12C-mutated non–small cell lung cancer. News release. Mirati Therapeutics. February 15, 2022. Accessed February 16. 2022.
  2. Mirati Therapeutics’ adagrasib receives breakthrough therapy designation from U.S. Food and Drug Administration for patients with advanced non–small cell lung cancer harboring the KRAS G12C mutation. News release. Mirati Therapeutics. June 24, 2021. Accessed February 16, 2022.
  3. Mirati Therapeutics announces positive phase 2 topline results for investigational adagrasib in patients with KRAS G12C-mutated advanced non–small cell lung cancer. News release. Mirati Therapeutics, Inc. September 20, 2021. Accessed February 16, 2022.
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