Bezuclastinib Submitted to FDA for Patients With Previously Treated GIST

Cogent Biosciences announced that it has submitted a new drug application to the U.S. Food and Drug Administration (FDA) for bezuclastinib for patients with gastrointestinal stromal tumors (GIST) who have previously been treated with Gleevec (imatinib). The submission seeks to provide a new option for patients whose cancer has progressed after first-line therapy.

The application is based on results from the phase 3 PEAK trial. It was submitted under the FDA’s Real-Time Oncology Review program, which is designed to allow a more streamlined review process. Earlier this year, bezuclastinib received breakthrough therapy designation for gastrointestinal stromal tumors.

What did the study show for patients with GIST?

The phase 3 PEAK study looked at adding bezuclastinib to Sutent (sunitinib) and compared it with Sutent alone in people with GIST whose cancer had already been treated with Gleevec.

One of the main things researchers measured was how long patients lived before their cancer started growing again.

Patients who received both bezuclastinib and Sutent went a median of 16.5 months without their cancer worsening. Those who received Sutent alone went a median of 9.2 months before their cancer grew or spread.

Overall, the combination treatment lowered the risk of the cancer getting worse or leading to death by 50% compared with Sutent alone.

The study also looked at how many patients had their tumors shrink. Among patients whose cancer no longer responded to Gleevec, 46% of those who received the combination had meaningful tumor shrinkage, compared with 26% of those who received Sutent alone.

At the time researchers reviewed the data, patients receiving the combination had stayed on treatment for an average of more than 19 months.

How was the PEAK trial designed?

PEAK is a global, randomized phase 3 clinical trial that enrolled patients with gastrointestinal stromal tumors who had previously received Gleevec.

Patients were randomly assigned to receive either the combination of bezuclastinib and Sutent or Sutent alone, which is considered the current standard of care after imatinib treatment.

The primary endpoint of the study was progression-free survival, which was assessed by blinded independent central review.

Cogent Biosciences plans to present the full trial results at a major medical meeting during the first half of 2026.

The company also announced plans to begin a phase 2 trial evaluating the combination in first-line patients with GIST who have exon 9 mutations and are naive to, or recently started, treatment with Gleevec.

In addition, a separate new drug application submission for bezuclastinib in advanced systemic mastocytosis remains on track for the first half of 2026.

Cogent is also working with the FDA to provide Expanded Access Programs in the United States for eligible patients with GIST or systemic mastocytosis who may benefit from bezuclastinib or the combination with Sutent.

What do we know about side effects?

According to the company, the combination of bezuclastinib and Sutent was generally well tolerated.

No unique risks were observed compared with the known safety profile of Sutent. Specific side effects were not detailed in the announcement.

References

1. “Pivotal Data From the Phase 3 PEAK Trial of Bezuclastinib in Combination With Sunitinib in Gastrointestinal Stromal Tumors” by Dr. Andrew Robbins, et al., press release.

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