Bristol Myers Squibb has disclosed detailed results from the phase 3 KRYSTAL-10 trial evaluating Krazati (adagrasib) in combination with Eli Lilly’s Erbitux (cetuximab) in patients with previously treated KRAS G12C-mutated metastatic colorectal cancer (mCRC). The study failed to achieve statistical significance on its dual primary endpoints of progression-free survival (PFS) and overall survival (OS).
The confirmatory trial enrolled 461 patients and compared the adagrasib-cetuximab regimen with chemotherapy. Its primary objectives were PFS and OS, while secondary endpoints focused on objective response rate (ORR) and safety. The results were presented at the ESMO Gastrointestinal Cancers Congress 2026 in Munich, Germany.
According to the data, patients receiving adagrasib plus cetuximab recorded a median PFS of 7.5 months, compared with 8.1 months in the chemotherapy arm. At a minimum follow-up of 26.4 months, median OS was 21.6 months for the adagrasib combination and 21.7 months for chemotherapy.
Bristol Myers Squibb reported that risk reductions for PFS and OS favored the adagrasib regimen by 11% and 17%, respectively. The company also pointed to a numerically higher ORR in the study-drug arm and stated that no new safety signals were identified during the trial.
The KRYSTAL-10 study was conducted as a confirmatory trial following the accelerated FDA approval of Krazati in combination with Erbitux for chemotherapy-experienced adults with KRAS-mutated locally advanced or metastatic colorectal cancer. That approval was granted in June 2024. Under the FDA’s accelerated approval pathway, confirmatory studies are required to further validate a therapy and support conversion to a traditional approval.
Commenting on the findings, a Bristol Myers Squibb spokesperson said: “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.”
The spokesperson also said the company is discussing the data and potential next steps with regulatory authorities. Bristol Myers Squibb added that it remains encouraged by the opportunity in lung cancer, where two pivotal first-line non-small cell lung cancer (NSCLC) trials are underway.
Krazati originally received an accelerated FDA approval in late 2022 for KRAS-mutated locally advanced or metastatic NSCLC. Bristol Myers Squibb acquired the drug through its $5.8 billion purchase of Mirati Therapeutics. The company reported that Krazati generated $205 million in revenue during 2025, representing growth of 62% compared with 2024.
In its presentation, Bristol Myers Squibb identified several trial limitations that it believes may have affected the results. The company cited challenges in interpreting PFS because some patients initiated subsequent therapies before blinded independent central review confirmation. It also noted that a higher proportion of patients in the chemotherapy group later received KRAS inhibitors, which it said may have confounded OS outcomes.
The company further stated that the open-label design of the study may have introduced bias in efficacy assessment and noted that treatment discontinuation was disproportionately high in the chemotherapy arm. Bristol Myers Squibb said further analyses of the data will be presented.
Beyond Krazati, Bristol Myers Squibb has approved colorectal cancer products Opdivo and Yervoy for a different patient population. The company is also conducting a phase 2/3 study of its BioNTech-partnered bispecific antibody pumitamig in combination with chemotherapy in patients with previously untreated, unresectable, or metastatic colorectal cancer.
Krazati has encountered a significant clinical setback after the Phase 3 KRYSTAL-10 study failed to achieve its primary endpoints in patients with metastatic colorectal cancer. The results represent an important development for Krazati, as researchers evaluate the findings and consider their impact on future regulatory and commercial strategies. Despite the disappointing outcome, the study provides valuable insights that may help guide future research in KRAS-targeted therapies.
Krazati Misses Primary Endpoints in KRYSTAL-10
The Phase 3 KRYSTAL-10 trial evaluated Krazati in patients with previously treated metastatic colorectal cancer carrying KRAS G12C mutations. Although expectations were high based on earlier clinical studies, Krazati did not demonstrate sufficient improvement in the predefined primary efficacy endpoints compared with the control treatment.
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