KRAZATI Plus Cetuximab Shows Promising Activity in Advanced KRAS G12C-Mutated CRC

In a recent development, Bristol Myers Squibb has reported significant findings from the KRYSTAL-1 study, which evaluated the efficacy of KRAZATI® (adagrasib) combined with cetuximab in treating patients with KRASG12C-mutated advanced colorectal cancer (CRC). The study's results, with a median follow-up of 11.9 months, indicated an objective response rate of 34%, a median progression-free survival of 6.9 months, and a median overall survival of 15.9 months among the 94 patients studied. The data were presented at the 2024 AACR annual meeting and are set to be published in Cancer Discovery.

KRASG12C mutations, which are oncogenic drivers, are found in 3-4% of CRC cases. Historically, single-agent cetuximab has not shown clinical benefits for patients with KRAS-mutated CRC. The KRYSTAL-1 study's positive findings suggest a potential breakthrough for patients who have historically faced poor prognoses and limited treatment options.

Scott Kopetz, M.D., Ph.D., from the University of Texas MD Anderson Cancer Center, emphasized the significance of these findings, noting that KRAS was previously considered 'undruggable.' The study's results reinforce the potential benefits of adagrasib for patients with KRASG12C-mutated CRC.

Bristol Myers Squibb's Anne Kerber highlighted the importance of identifying KRASG12C mutations in CRC patients, as it can guide the use of targeted treatment options. The FDA has accepted a supplemental new drug application for KRAZATI in combination with cetuximab for priority review, with a PDUFA goal date set for June 21, 2024.

KRAZATI (adagrasib) is a potent, highly selective oral inhibitor of KRASG12C, designed to sustain target inhibition, which is crucial given the KRASG12C protein's short half-life. The drug has been granted accelerated approval for treating KRASG12C-mutated non-small cell lung cancer (NSCLC) and is currently being evaluated in other solid tumors, including CRC.

The KRYSTAL-1 trial is an open-label, multicenter study aimed at determining the safety and efficacy of KRAZATI in patients with advanced solid tumors harboring a KRASG12C mutation. The study's primary endpoint was the objective response rate, with secondary endpoints including duration of response, progression-free survival, overall survival, and safety.

KRAZATI has been granted breakthrough therapy designation for use in combination with cetuximab in patients with advanced CRC whose cancer has progressed after prior treatments. The drug's prescribing information is available online.

CRC is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer-related deaths. Bristol Myers Squibb is dedicated to transforming patients' lives through scientific advancements in cancer research and treatment.

The company's commitment to addressing all aspects of cancer care, from diagnosis to survivorship, underscores its leadership in cancer care. Bristol Myers Squibb is a global biopharmaceutical company focused on discovering, developing, and delivering innovative medicines to help patients overcome serious diseases.