FDA Accepts Supplemental New Drug Application for Adagrasib for Colorectal Cancer


The sNDA was based on results from the KRYSTAL-1 study, evaluating the drug alone or in combination with other anti-cancer therapies in those with advanced solid tumors who have KRASG12C mutations.

The FDA accepted a supplemental new drug application (sNDA) for adagrasib (Krazati; Bristol Myers Squibb) in combination with cetuximab for the treatment of individuals with previously treated KRASG12C-mutated locally advanced or metastatic colorectal cancer (CRC), according to a press release. The agency assigned a Prescription Drug User Fee Act goal date for June 21, 2024.1

3d rendered illustration of the anatomy of a cancer cell | Image Credit: SciePro - stock.adobe.com

Image Credit: SciePro - stock.adobe.com

“Pretreated KRASG12C-mutated CRC is associated with poor outcomes and the current standard of care offers limited clinical benefit for patients,” Anne Kerber, MD, senior vice president and head of late clinical development in Hematology, Oncology, and Cell Therapy at Bristol Myers Squibb, said in a press release. “The acceptance of this filing for [adagrasib] in combination with cetuximab is a positive step toward providing a potential new option for patients and their physicians.”1

About the Krystal 1 Clinical Trial

Trial Name: Phase 1/​2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1

ClinicalTrials.gov ID: NCT03785249

Sponsor: Mirati Therapeutics Inc

Completion Date (Estimated): September 2024

The sNDA submission was based on results from the KRYSTAL-1 study (NCT03785249), evaluating the drug alone or in combination with other anti-cancer therapies in those with advanced solid tumors who have KRASG12C mutations. It was a multiple expansion cohort, phase 1/2 clinical trial with a primary endpoint for the phase 2 cohort of objective response rate (ORR). The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival, and safety, according to the press release.1

In the trial, those who received adagrasib as monotherapy received it orally at 600 mg twice daily while the other group received it the same dosage in combination with intravenous cetuximab with a loading dose of 400 mg per square meter of body-surface area and either a dose of 250 mg per square meter once weekly or every 2 weeks at 500 mg per square meter, according to the study authors.2

Investigators randomized treatment with the monotherapy to 44 individuals and the combination therapy to 32 individuals, who had median follow-up of 20.1 months and 17.5 months, respectively. A response was reported for approximately 19% of individuals in the monotherapy group with a median DOR of 4.3 months and PFS of 5.6 months. However, according to the study authors, for the combination therapy, there was a response of 46% out of 28 evaluable patients, a DOR of 7.6 months, and median PFS of 6.9 months.2

Furthermore, there were no grade 5 adverse events (AEs) observed. The percentage of grade 3 and 4 treatment-related AEs was 34% in the monotherapy group and 16% in the combination group, according to the study authors.2

In 2022, the drug was granted breakthrough therapy designation in combination with cetuximab in individuals with KRASG12C-mutated advanced CRC whose cancer progressed following treatment with chemotherapy and an anti-VEGF therapy. Additionally, it was granted accelerated approval for treatment of individuals with KRASG12C-mutated locally advanced or metastatic non–small cell lung cancer who received at least 1 prior systemic therapy based on the ORR and DOR.1

  1. US Food and Drug Administration (FDA) Accepts Supplemental New Drug Application for Krazati (adagrasib) in Combination with Cetuximab as a Targeted Treatment Option for Patients with Previously Treated KRAS G12C-Mutated Locally Advanced or Metastatic Colorectal Cancer (CRC) for Priority Review. News release. Bristol Myers Squibb. February 20, 2024. Accessed February 26, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-FDA-Accepts-Supplemental-New-Drug-Application-for-KRAZATI-adagrasib-in-Combination-with-Cetuximab-as-a-Targeted-Treatment-Option-for-Patients-with-Previously-Treated-KRAS-G12C-Mutated-Locally-Advanced-or/default.aspx
  2. Yaeger R, Weiss J, Pelster MS, Spira AI, et al. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023;388(1):44-54. doi:10.1056/NEJMoa2212419
Related Videos
Team of care workers with women at the center -- Image credit: Delmaine Donson/peopleimages.com | stock.adobe.com
© 2024 MJH Life Sciences

All rights reserved.