Krazati (adagrasib) + cetuximab) demonstrates clinically meaningful activity as a targeted treatment for patients with previously treated KRAS G12C mutated locally advanced or metastatic colorectal cancer

These late breaking data (abstract #CT013) will be featured in an oral presentation at the 2024 American Association for Cancer Research (AACR) annual meeting on Monday, April 8 at 11:10 a.m. Pacific Time and will be highlighted as part of the meeting’s official press program. The data will also be published simultaneously in Cancer Discovery.

With a median follow up of 11.9 months in 94 patients, Krazati plus cetuximab demonstrated an objective response rate, the primary endpoint, of 34%, median progression-free survival of 6.9 months (95% CI, 5.7-7.4), and median overall survival of 15.9 months (95% CI, 11.8-18.8) in pre-treated patients with KRASG12C-mutated locally advanced or metastatic CRC. The median duration of response was 5.8 months. Disease control was observed in 85% of patients. The safety profile for Krazati plus cetuximab was manageable and consistent with previous reports, and with the known safety profile of each drug individually.

KRASG12C mutations act as oncogenic drivers and occur in approximately 3-4% of colorectal cancers. In previous studies, treatment with cetuximab as a single agent did not offer a clinical benefit in patients with KRAS-mutated colorectal cancer.

“Patients with KRASG12C-mutated colorectal cancer have historically faced poor prognoses and remain in need of additional treatment options,” said Scott Kopetz, M.D., Ph.D, FACP, associate vice president for translational research, and Professor, Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “Although KRAS had previously been considered ‘undruggable,’ these data from KRYSTAL-1 reinforce the potential benefit of adagrasib for these specific patients.”

“While there has been progress in the treatment of colorectal cancer, there remain groups of patients, such as those with KRAS-mutated cancers, who continue to need new, targeted treatment options,” said Anne Kerber, senior vice president, head of late clinical development, Hematology, Oncology, Cell Therapy (HOCT) at Bristol Myers Squibb. “These data highlight the significance of testing and identification of KRASG12C mutations in patients with CRC.”

The company announced in February 2024 that the FDA had accepted a supplemental new drug application for Krazati in combination with cetuximab as a targeted treatment option for patients with previously treated KRASG12C-mutated locally advanced or metastatic CRC for priority review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 21, 2024.