Patients treated with Bristol Myers Squibb’s Krazati in combination with cetuximab saw shorter median overall and progression-free survival than comparators on chemotherapy.
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.
These findings come from the Phase 3 confirmatory KRYSTAL-10 study, which combined Krazati with Lilly’s cetuximab, a colorectal cancer (CRC) drug marketed as Erbitux. KRYSTAL-10 enrolled more than 460 patients with metastatic CRC who carry the G12C KRAS mutation, and whose disease progressed after first-line chemotherapy.
BMS’ Krazati regimen failed the trial’s primary efficacy endpoints, according to a presentation last Thursday at the European Society for Medical Oncology’s 2026 Gastrointestinal Cancers congress. Patients treated with the investigational combo reached a median progression-free survival of 7.5 months, while comparators on chemo hit 8.1 months. Median overall survival, meanwhile, was 21.6 months in the Krazati arm versus 21.7 months in controls.
The pharma documented “numerically higher” overall response rates in patients who received Krazati plus cetuximab but presented no statistical analysis.
“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.”
Designed to be taken orally, Krazati is a small-molecule and irreversible inhibitor of G12C-mutated KRAS, a key signaling driver in several cancers. The drug was originally developed by Mirati Therapeutics, which BMS bought in October 2023 for $4.8 billion.
Krazati first won an FDA nod in December 2022 for non-small cell lung cancer (NSCLC) and then again in June 2024 for KRAS G12C-mutated CRC. Both approvals were given under the agency’s accelerated pathway, which requires drug sponsors to verify their product’s clinical benefit in a confirmatory trial. KRYSTAL-10 was supposed to serve this function for Krazati’s CRC indication.
In NSCLC, Krazati in 2024 met the goal of its primary confirmatory trial, significantly improving progression-free survival in the Phase 3 KRYSTAL-12 trial, which tested the drug as a second-line or later treatment option. Krazati is being studied in two pivotal trials for first-line NSCLC, the company spokesperson said.
Outside of BMS-led programs, Krazati is also being studied by Kura Oncology alongside the biotech’s farnesyltransferase blocker darlifarnib. A first-in-human readout in May demonstrated a 67% objective response rate in pancreatic cancer, 50% in NSCLC and 29% in CRC.
Update (July 7): This story has been updated to include statements from BMS.
