Key Takeaways:
- Bezuclastinib combo reduced progression or death risk by 50% versus sunitinib alone
- Median PFS reached 16.5 months compared with 9.2 months for standard of care
- FDA set a PDUFA target action date of Nov. 30, 2026 with Priority Review
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Cogent's bezuclastinib combo cuts GIST progression risk by 50% in Phase 3
Cogent's bezuclastinib combo cut GIST progression or death risk by 50% in a Phase 3 trial, the first treatment to beat an active comparator in the disease.
"The results presented today clearly demonstrate that the combination of bezuclastinib and sunitinib provides impressive clinical activity for patients with KIT-driven gastrointestinal stromal tumors," Andrew Wagner, senior physician at Dana-Farber Cancer Institute and associate professor at Harvard Medical School, said. "I expect it will be rapidly adopted as the new standard of care for patients with second-line GIST."
The PEAK trial enrolled patients with imatinib-resistant or intolerant advanced GIST. Median progression-free survival reached 16.5 months for the bezuclastinib combination versus 9.2 months for sunitinib monotherapy (hazard ratio of 0.50, 95% CI: 0.39-0.65, p<0.0001). The objective response rate was 46% versus 26%, respectively. Overall survival data remain immature.
The U.S. Food and Drug Administration accepted Cogent's New Drug Application for the combination with Priority Review and assigned a Prescription Drug User Fee Act target action date of Nov. 30, 2026. The agency communicated no plan to hold an advisory committee meeting. Cogent also initiated a 40-patient extension cohort evaluating the combination in first-line GIST patients with KIT exon 9 primary mutations.
The bezuclastinib combination was generally well tolerated, with no unique risks observed compared with the known safety profile of sunitinib alone. Grade 3 or higher adverse events in the combination arm versus sunitinib included hypertension (29.4% vs 27.4%), neutropenia (15.2% vs 15.4%), ALT/AST elevation (10.8% vs 1.4%), anemia (9.3% vs 4.8%) and diarrhea (7.8% vs 7.2%). Hepatic events were predominantly transient and manageable, with all Grade 3 ALT/AST elevations resolving and no Grade 4 elevations reported. Treatment discontinuation due to adverse events occurred in 7.4% of patients on the combination versus 3.8% on sunitinib alone.
The mean duration of treatment for patients receiving the bezuclastinib combination was estimated at 21.4 months as of March 31, 2026. Median PFS2 — time from randomization to progression on the next line of therapy or death — was not reached versus 21 months (HR=0.57, 95% CI: 0.41-0.78), reinforcing the durability of benefit.
The data position Cogent for a potential second-half 2026 launch in both GIST and systemic mastocytosis. The company has established expanded access programs for eligible U.S. patients. Investors will watch the PDUFA date and any advisory committee developments ahead of the Nov. 30 decision.
This article is for informational purposes only and does not constitute investment advice.
[1] Cogent Biosciences Announces Detailed Clinical Data from PEAK Phase 3 Trial with Bezuclastinib in Combination with Sunitinib in Gastrointestinal Stromal Tumors (GIST) at 2026 American Society of Clinical Oncology (ASCO) Annual Meeting[2] Cogent Biosciences Announces Detailed Clinical Data from PEAK Phase 3 Trial with Bezuclastinib in Combination with Sunitinib in Gastrointestinal Stromal Tumors (GIST) at 2026 ...[3] Cogent Biosciences Announces FDA Acceptance of New Drug Application (NDA) with Priority Review for Bezuclastinib in Combination with Sunitinib for Patients with GIST[4] Cogent Biosciences, Inc.: Cogent Biosciences Announces FDA Acceptance of New Drug Application (NDA) with Priority Review for Bezuclastinib in Combination with Sunitinib for ...[5] Bezuclastinib/Sunitinib NDA Accepted for Priority Review in Advanced GIST
