FDA has accepted Cogent Biosciences’ NDA for bezuclastinib plus sunitinib in second‑line GIST, granting Priority Review with a PDUFA date of November 30, 2026, supported by positive Phase 3 PEAK trial results.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has accepted Cogent Biosciences’ New Drug Application (NDA) for bezuclastinib in combination with sunitinib for patients with gastrointestinal stromal tumor (GIST) previously treated with imatinib. The agency granted Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of November 30, 2026. Priority Review shortens the FDA’s review timeline to six months.
The FDA also indicated it does not currently plan to convene an advisory committee meeting and has not identified potential review issues at this stage.
Clinical Context
Bezuclastinib is an investigational selective KIT D816V inhibitor targeting genetically defined diseases driven by KIT mutations. In GIST, resistance to frontline imatinib frequently arises through secondary KIT mutations, leaving patients with limited durable treatment options after progression. Sunitinib remains the standard second-line therapy, though response durability and tolerability continue to present clinical challenges.
Phase 3 PEAK Trial Results
The NDA is supported by the global Phase 3 PEAK trial (NCT05208047), which compared bezuclastinib plus sunitinib against sunitinib monotherapy in patients with imatinib-resistant or intolerant GIST.
As of the September 30, 2025 cutoff, the combination reduced the risk of disease progression or death by 50% versus sunitinib alone, meeting the trial’s primary endpoint of progression-free survival (PFS). The hazard ratio was 0.50 (95% CI: 0.39–0.65).
Median PFS reached 16.5 months with the combination versus 9.2 months with sunitinib monotherapy based on blinded independent central review. Objective response rates also improved, with 46% of patients in the combination arm achieving a response compared with 26% in the sunitinib arm. Overall survival data remain immature.
Safety Profile
The regimen was generally well tolerated and consistent with the known safety profile of sunitinib. Common Grade 3 or higher treatment-emergent adverse events included hypertension, neutropenia, elevated ALT/AST, anemia, and diarrhea.
Treatment discontinuation due to treatment-related adverse events occurred in 7.4% of patients receiving the combination and 3.8% receiving sunitinib alone.
Liver-related adverse events were primarily transient and manageable laboratory abnormalities. Grade 3 ALT/AST elevations resolved in all affected patients, and no Grade 4 elevations were reported.
Expert and Regulatory Outlook
Andrew Robbins, President and Chief Executive Officer of Cogent Biosciences, said the FDA acceptance represents “a major milestone for the company and reflects the strength of the PEAK trial results.” He emphasized Cogent’s commitment to advancing innovative therapies for patients with genetically defined cancers.
Cogent plans to present full PEAK trial results at the ASCO Annual Meeting 2026. The company is also preparing for potential commercial launches of bezuclastinib in both GIST and systemic mastocytosis later this year. In parallel, Cogent has established U.S. Expanded Access Programs
Reference
About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.