Bezuclastinib and Sutent Combo Shows Improved Outcomes in GIST

For patients with Gleevec (imatinib)-resistant or intolerant gastrointestinal stromal tumors (GIST), treatment with bezuclastinib (CGT9486) in combination with Sutent (sunitinib) demonstrated longer time before the disease progressed and a higher rate of tumor response compared with Sutent alone, according to data from the phase 3 PEAK trial.

These findings were shared in a Cogent Biosciences, Inc. news release. For many patients, treatment options after Gleevec have remained limited for approximately two decades. These new findings suggest that the bezuclastinib combination may offer a meaningful new second-line treatment option, according to the news release.

“It is a historic day for Cogent Biosciences and the GIST patient community,” said Andrew Robbins, Cogent’s president and CEO. “We are extremely excited to announce positive results from the phase 3 PEAK trial of bezuclastinib plus Sutent, which have far surpassed our expectations for the activity of this combination in patients with Gleevec-resistant or intolerant GIST. With these incredible results … the bezuclastinib combination is poised to become the new standard of care for treatment of second-line GIST patients. We are pleased to have an existing Expanded Access Program available to GIST patients who have an urgency to access this novel treatment immediately and look forward to partnering with regulatory agencies to make this combination broadly available to patients as soon as possible.”

Based on these outcomes, Cogent Biosciences plans to submit a new drug application to the U.S. Food and Drug Administration (FDA) in the first half of 2026. A detailed presentation of the full PEAK results is also expected at a scientific conference during the same timeframe.

Phase 3 PEAK Trial Shows Improved Progression-Free Survival and Higher Objective Response Rate

The PEAK trial compared bezuclastinib plus Sutent against Sutent alone in patients whose GIST had progressed on or who could not tolerate previous treatment with Gleevec. The primary end point in this study was progression-free survival (PFS), which reflects the length of time the disease does not worsen.

Patients receiving the bezuclastinib combination experienced a median PFS of 16.5 months. In contrast, patients treated with Sutent alone reached 9.2 months. This represents a significant improvement and corresponds to a 50% reduction in the risk of disease progression or death.

According to the company, these results make the PEAK trial the first positive phase 3 study in the second-line GIST setting in more than 20 years. Additionally, the estimated mean duration of treatment for the bezuclastinib combination is projected to exceed 19 months based on ongoing patient follow-up.

“The results from the PEAK trial are truly transformative and practice changing,” said Dr. Neeta Somaiah, professor and chair of the Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, in Houston. “Following regulatory approval, I expect the bezuclastinib combination to be rapidly adopted as the new standard of care treatment for the majority of patients in the second-line GIST setting.”

The bezuclastinib combination also produced an objective response rate (ORR) of 46% compared with 26% in patients receiving Sutent alone. This indicates that tumors shrank or showed clear signs of response at nearly double the rate seen with Sutent alone.

“Gleevec-resistant or intolerant GIST patients have waited nearly 20 years for a new second-line treatment option. The remarkable results of the PEAK study suggest that wait has come to an end,” said Sara Rothschild, executive director of the Life Raft Group. “Like so many in the GIST community, we’ve actively followed this trial with real anticipation. On behalf of GIST patients around the world, we share our excitement for the hope that the bezuclastinib combination may bring these patients and their families.”

Safety Profile and Next Steps Toward FDA Submission

The safety findings from the PEAK trial showed that the combination of bezuclastinib and Sutent was generally well tolerated. No unexpected risks were identified compared with the known safety profile of Sutent. Reported side effects included hypertension, neutropenia, elevations in liver enzymes, anemia and diarrhea. The rates of these side effects were comparable between the two treatment arms, and most liver-related events were described as manageable, reversible and not severe.

A small percentage of patients discontinued treatment due to side effects, but the rate remained relatively low. Importantly, no grade 4 (life-threatening) liver enzyme elevations were observed, and all grade 3 (severe) elevations resolved.

Cogent Biosciences is continuing to analyze the trial data and will release more complete findings in 2026. The company plans to work with regulatory agencies to advance the approval process and make this treatment option more widely available.

Reference

1. “Cogent Biosciences Reports Positive Results from Bezuclastinib PEAK Phase 3 Trial in Gastrointestinal Stromal Tumors (GIST),” by Cogent Biosciences, Inc. News release; Nov. 10, 2025.

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