“Bristol Myers Squibb (NYSE: BMY) announced today 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), confirmed by an FDA-approved test, who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. This approval is based on objective response rate (ORR) and duration of response (DOR) data from the Phase 1/2 KRYSTAL-1 study. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
“This approval marks a significant advancement for patients with historically challenging KRASG12C-mutated CRC,” said Rona Yaeger, MD, Gastrointestinal Oncologist & Early Drug Development Specialist at Memorial Sloan Kettering Cancer Center. “KRAZATI combined with cetuximab offers a new treatment option when prior therapies have been ineffective.”
In the KRYSTAL-1 study, which evaluated KRAZATI (600 mg tablets orally twice daily) with cetuximab in heavily pretreated CRC patients, the combination demonstrated a 34% confirmed ORR with a median DOR of 5.8 months. Current late-line treatments typically yield ORRs of only 1-6% post-progression on chemotherapy ± VEGF/VEGFR inhibitors.
KRAZATI carries warnings for gastrointestinal adverse reactions, QTc interval prolongation, hepatotoxicity, and interstitial lung disease (ILD)/pneumonitis.
“We are proud to expand our oncology portfolio with the FDA’s approval of KRAZATI for KRASG12C-mutated CRC, marking its second U.S. approval,” said Wendy Short Bartie, Senior Vice President, U.S. Oncology and Hematology at Bristol Myers Squibb. “This milestone underscores our commitment to delivering innovative cancer treatments.”
In 2022, KRAZATI received breakthrough therapy designation for use in combination with cetuximab in KRASG12C-mutated advanced CRC.
KRAZATI, an irreversible KRASG12C inhibitor with a long half-life and CNS penetration, was developed with a tissue-based companion diagnostic (CDx) by QIAGEN.
KRYSTAL-1 is an open-label Phase 1/2 trial evaluating KRAZATI’s safety and efficacy in advanced CRC with KRASG12C mutations, funded by Mirati Therapeutics, Inc., a Bristol Myers Squibb company.
The safety profile of KRAZATI plus cetuximab in KRASG12C-mutated CRC patients aligns with previous reports, with common adverse reactions including rash, nausea, diarrhea, and fatigue.”
