Bristol Myers Squibb gets USFDA accelerated approval for Krazati, Cetuximab combo for colorectal cancer
Princeton: Bristol Myers Squibb has announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for KRAZATI (adagrasib) in combination with cetuximab as a targeted treatment option for adult patients with KRASG12C -mutated locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR) results. Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial.
“CRC with a KRASG12C mutation occurs in approximately 3-4% of CRC patients and has historically been challenging to treat,” said Rona Yaeger, MD, Gastrointestinal Oncologist & Early Drug Development Specialist, Memorial Sloan Kettering Cancer Center. “The FDA approval of KRAZATI combined with cetuximab now provides a new treatment option to these patients when their tumors do not respond well to prior therapies.”
The approval is based on results from cohorts of the Phase 1/2 KRYSTAL-1 open-label study which evaluated KRAZATI (600 mg tablets administered orally twice daily) in combination with cetuximab in 94 patients with heavily pretreated CRC harboring a KRASG12C mutation. The study met its primary endpoint, with a confirmed ORR of 34% (n=94, 95% CI: 25-45) for KRAZATI with cetuximab, all of which were partial responses. The median DOR, one of the secondary endpoints, was 5.8 months (95% CI: 4.2-7.6). Current late-line standard of care options result in limited response rates (ORR 1-6%) after progression on chemotherapy ± VEGF/VEGFR inhibitors.
KRAZATI is associated with the following Warnings & Precautions: Gastrointestinal adverse reactions including diarrhea, nausea, and vomiting, QTc interval prolongation, hepatotoxicity, and interstitial lung disease (ILD)/pneumonitis.
“The approval of KRAZATI in CRC is the second in the U.S. for this therapy and the first for BMS' recently expanded oncology portfolio. This is an important milestone for BMS and the patients we serve as we deliver on our commitment to provide innovative medicines for cancer,” said Wendy Short Bartie, senior vice president, U.S. Oncology and Hematology at Bristol Myers Squibb. “We are proud to make KRAZATI - the first KRASG12C inhibitor to be FDA approved beyond non-small cell lung cancer - available to CRC patients, and look forward to further evaluating KRAZATI through our ongoing development program.”
In 2022, the FDA granted breakthrough therapy designation for KRAZATI in combination with cetuximab for patients with KRASG12C -mutated advanced CRC whose cancer has progressed following prior treatment with certain chemotherapy and an anti-VEGF therapy.
KRAZATI is an irreversible inhibitor of KRASG12C with a long half-life (23 hours), dose-dependent pharmacokinetics (PK), and central nervous system (CNS) penetration, which, in combination with cetuximab may enhance inhibition of KRAS-dependent signaling or overcome adaptive feedback.
The company partnered with QIAGEN to develop a tissue-based companion diagnostic (CDx) for KRAZATI that is now available.
KRAZATI is a registered trademark of Mirati Therapeutics, Inc., a Bristol Myers Squibb company.
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