Bristol Myers Squibb’s RAS inhibitor Krazati, when used alongside the EGFR blocker cetuximab, failed to significantly improve survival in certain patients with colorectal cancer, according to a presentation at the European Society for Medical Oncology’s 2026 Gastrointestinal Cancers congress on July 7.
The Phase 3 confirmatory KRYSTAL-10 study combined Krazati with Lilly’s cetuximab, marketed as Erbitux. The trial enrolled more than 460 patients with metastatic colorectal cancer who carry the G12C KRAS mutation and whose disease progressed after first-line chemotherapy. Patients treated with the investigational combination reached a median progression-free survival of 7.5 months, while those on chemotherapy had a median of 8.1 months. Median overall survival was reported as 21.6 months in the Krazati arm compared to 21.7 months in controls.
Bristol Myers Squibb documented “numerically higher” overall response rates among patients who received Krazati plus cetuximab but did not present statistical analysis for these results.
“While the study did not meet its primary endpoints, results from the final analysis of the study presented at ESMO GI support the clinical activity of the adagrasib plus cetuximab combination in this patient population,” a company spokesperson told BioSpace in an email, adding that BMS is “discussing the data and potential next steps with regulatory authorities.”
Krazati is designed as an oral small-molecule and irreversible inhibitor targeting G12C-mutated KRAS, which plays a role in several cancers. The drug was originally developed by Mirati Therapeutics before Bristol Myers Squibb acquired Mirati for $4.8 billion in October 2023.
Krazati received accelerated approval from the Food and Drug Administration for non-small cell lung cancer (NSCLC) in December 2022 and for KRAS G12C-mutated colorectal cancer in June 2024; both approvals required confirmatory trials such as KRYSTAL-10 to verify clinical benefit. In NSCLC, Krazati met its primary endpoint by improving progression-free survival during its Phase 3 confirmatory trial (KRYSTAL-12), as reported by Bristol Myers Squibb.
