BMS’s KRAS Inhibitor Krazati Receives FDA Approval for Colorectal Cancer Treatment

1. FDA Approval: The FDA granted accelerated approval to Bristol Myers Squibb's (BMS) KRAS inhibitor Krazati (adagrasib) in combination with cetuximab for treating adults with KRAS G12C-mutated locally advanced or metastatic colorectal cancer who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
2. Efficacy: The approval was based on the KRYSTAL-1 trial, which showed a confirmed overall response rate (ORR) of 34% and a median duration of response (DOR) of 5.8 months. Thirty-one percent of responding patients had a DOR of at least 6 months.
3. Dosing: The recommended dose of adagrasib is 600 mg orally twice daily until disease progression or unacceptable toxicity.
4. Side Effects: Common adverse reactions include rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.
5. Market Impact: This approval cements Krazati's lead over Amgen's Lumakras in the KRAS inhibitor market, particularly in colorectal cancer treatment.
6. Future Studies: BMS may need to conduct a confirmatory trial to maintain the FDA approval, while Amgen is working on a full approval for Lumakras and also pursuing approval in colorectal cancer.