FDA Grants Designation to Bezuclastinib Combo in Advanced GIST

The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to bezuclastinib used in combination with Sutent (sunitinib) for patients with gastrointestinal stromal tumors (GIST) whose disease has stopped responding to standard therapy and have been previously treated with Gleevec (imatinib), according to a news release from Cogent Biosciences.

Notably, according to the news release, breakthrough therapy designation is reserved for treatments targeting serious or life-threatening diseases that show early clinical evidence of substantial improvement over existing options. When granted, the designation allows for closer collaboration with the FDA and can speed the development and review process.

“We are excited to announce this breakthrough therapy designation which recognizes the potential for the bezuclastinib combination to substantially improve upon the currently available treatment options for patients with Gleevec-resistant GIST,” said Andrew Robbins, Cogent’s president and CEO. “We look forward to the continued collaboration with the FDA as we work to bring the first new treatment option in over twenty years to this patient population.”

The designation follows results from the phase 3 PEAK clinical trial and signals that the FDA sees the potential for this combination to meaningfully improve outcomes for patients facing limited treatment options.

According to Cogent, this combination could represent the first new treatment option in more than 20 years for patients with Gleevec-resistant disease.

Understanding GIST and Current Treatment Challenges

GIST is a rare type of cancer that begins in the digestive tract and often involves mutations in KIT or PDGFRA genes. Gleevec is typically used as first-line therapy and can be effective for many patients. However, resistance commonly develops over time, leaving patients with fewer effective options.

Sutent is often used after Gleevec stops working, but responses can be modest and temporary. As a result, there is a strong need for therapies that can provide longer disease control without significantly worsening quality of life.

Key Findings From the PEAK Trial in GIST

The breakthrough therapy designation is based on data showing that the bezuclastinib plus Sutent combination significantly delayed disease progression compared with Sutent alone, which is a commonly used treatment after Gleevec progression.

In the PEAK trial, the combination reduced the risk of disease progression or death by 50% compared with standard therapy. Median progression-free survival was 16.5 months for patients receiving the combination, compared with 9.2 months for those treated with Sutent alone, as assessed by blinded independent central review.

Importantly for patients, the combination was generally well tolerated. Investigators did not identify new safety concerns beyond what is already known for Sutent, suggesting that the added benefit did not come at the cost of unexpected toxicity.

The PEAK trial compared bezuclastinib plus Sutent with Sutent alone in patients with GIST who had previously received Gleevec. Progression-free survival was the primary endpoint, meaning researchers measured how long patients lived without their cancer worsening.

The trial results showed a statistically significant and clinically meaningful benefit favoring the combination therapy, supporting the FDA’s decision to grant Breakthrough Therapy Designation.

Patients enrolled in the PEAK trial had advanced GIST and had already been treated with Gleevec. This population reflects a real-world group of patients who often face disease progression and limited treatment options after first-line therapy.

Cogent plans to expand its research by launching a phase 2 trial in mid-2026 that will evaluate the combination in patients with exon 9–mutated GIST who are either new to Gleevec or recently started treatment.

Additional Regulatory and Research Updates

Earlier this month, the FDA also agreed to accept Cogent’s new drug application for the bezuclastinib combination under the Real-Time Oncology Review program. This pathway allows portions of the application to be reviewed before the full submission is complete, potentially accelerating access if the therapy is approved.

Cogent expects to complete the full new drug application submission in April 2026 and plans to present detailed PEAK trial results at a major medical meeting in the first half of the year.

Although approval is not yet guaranteed, the breakthrough therapy designation highlights the therapy’s potential to improve outcomes and underscores the urgency of bringing new options to this patient community.

Reference

1. “Cogent Biosciences Announces Breakthrough Therapy Designation For Bezuclastinib In Combination With Sunitinib For Patients With Gastrointestinal Stromal Tumors (GIST),” by Cogent Biosciences Inc. News release; Jan. 26, 2026.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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