Cogent's Bezuclastinib-Sunitinib Combo Nearly Doubles Progression-Free Survival in Second-Line GIST, the First Positive Phase 3 in Two Decades
Cogent's bezuclastinib plus sunitinib reached 16.5-month median PFS versus 9.2 months in second-line GIST, with FDA Priority Review and a November 30 PDUFA date.
Overview
Cogent Biosciences has reported detailed Phase 3 results showing that adding its investigational drug bezuclastinib to sunitinib nearly doubled progression-free survival in patients with gastrointestinal stromal tumors (GIST) whose disease had progressed after imatinib. According to BioSpace, the company called the PEAK study the “First positive Phase 3 trial in second-line GIST patients in over 20 years.” The U.S. Food and Drug Administration has since accepted the combination for review under Priority Review, Cogent announced, setting a target action date of November 30, 2026.
What We Know
The global, randomized PEAK trial (NCT05208047) randomized 413 patients with advanced KIT-mutant GIST that was imatinib-resistant or intolerant, 1:1 to bezuclastinib 600 mg once daily plus sunitinib 37.5 mg once daily (n=204) or sunitinib 37.5 mg once daily alone (n=209), according to CancerNetwork.
The combination produced a median progression-free survival of 16.5 months (95% CI, 13.8–19.2) versus 9.2 months (95% CI, 7.2–11.0) for sunitinib alone, with a hazard ratio of 0.50 (95% CI, 0.39–0.65; p<.0001), CancerNetwork reported. That figure was assessed by blinded independent central review, according to AllSci. The objective response rate was 45.6% with the combination versus 25.8% with sunitinib monotherapy (P<.0001), per CancerNetwork.
On a secondary measure, second progression-free survival (PFS2) had not been reached in the combination arm versus 21 months for sunitinib (HR, 0.57; 95% CI, 0.41–0.78), Cogent reported. The mean treatment duration in the combination arm was 21.4 months, the company said.
The detailed data were presented on May 30, 2026, at the American Society of Clinical Oncology (ASCO) Annual Meeting by Andrew J. Wagner, MD, PhD, Chief Medical Officer and Medical Director of Adult Ambulatory Oncology at Dana-Farber Cancer Institute, according to CancerNetwork. “I am very excited about the potential for this combination and expect it will be rapidly adopted as the new standard of care for patients with second-line GIST,” Wagner said in Cogent’s statement.
Bezuclastinib is described as a “selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17,” according to Cogent.
Safety
Grade 3 or higher treatment-related adverse events occurred in 71.6% of the combination arm versus 52.4% with sunitinib alone, and treatment discontinuation rates were 7.4% versus 3.8%, CancerNetwork reported. Among specific Grade 3-or-higher events, hypertension occurred in 29.4% of combination patients versus 27.4% on sunitinib, neutropenia in 15.2% versus 15.4%, and increased ALT/AST in 10.8% versus 1.4%, according to Cogent.
Regulatory Path
The FDA accepted the New Drug Application for bezuclastinib in combination with sunitinib for GIST patients who have received prior treatment with imatinib and granted it Priority Review, with a target action date of November 30, 2026, Cogent announced. The company said the agency has “no plan to hold an advisory committee, nor have they identified any potential review issues,” per the same release. Cogent President and CEO Andrew Robbins said the company plans “to launch bezuclastinib later this year,” according to its ASCO release, and noted that preparations for launches “in both GIST and systemic mastocytosis later this year are well underway,” per the NDA release.
Context
Sunitinib has been the standard second-line option for GIST since its approval, with “no new approved therapy since sunitinib’s approval nearly two decades ago,” AllSci noted. AllSci framed the result as positioning bezuclastinib plus sunitinib “as the first regimen to demonstrate a statistically significant PFS advantage over sunitinib monotherapy in a randomized trial in post-imatinib GIST,” the outlet wrote.
What We Don’t Know
Overall survival data from PEAK were not detailed in these readouts, and the trial’s PFS2 endpoint in the combination arm had not yet been reached at the data cutoff, leaving the durability of the benefit beyond the reported follow-up an open question. Whether the FDA will approve the combination by its November 30, 2026, target date, and on what label, remains to be determined.