Cogent Biosciences submits NDA to the U.S. Food and Drug Administration for bezuclastinib in second-line GIST, supported by Phase 3 PEAK trial showing significant PFS and ORR improvement.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Cogent Biosciences has completed submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration for bezuclastinib in patients with gastrointestinal stromal tumors (GIST) who have received prior treatment with imatinib. The application is being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program and follows the therapy’s earlier Breakthrough Therapy Designation in GIST.
The filing is supported by results from the global Phase 3 PEAK trial (NCT05208047), which evaluated bezuclastinib in combination with sunitinib versus sunitinib monotherapy in second-line GIST. The combination achieved a statistically significant improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 50% (HR 0.50; 95% CI: 0.39–0.65).
Median PFS reached 16.5 months with the combination compared to 9.2 months with sunitinib alone, as assessed by blinded independent central review. The regimen also demonstrated a higher objective response rate (ORR), with 46% of patients responding versus 26% in the control arm, particularly in imatinib-resistant patients.
The combination was generally well tolerated, with no new safety signals beyond the known profile of sunitinib. Overall survival data remain immature. Based on ongoing treatment exposure, the estimated mean duration of therapy with the combination is projected to exceed 19 months.
Commenting on the NDA submission and PEAK trial results, Andrew Robbins said the milestone reflects confidence in the strength of the data and the potential of the bezuclastinib combination to meaningfully improve outcomes in second-line GIST, while acknowledging the contributions of patients, investigators, and study teams.
Cogent plans to present full results from the PEAK trial at a major medical meeting in the first half of 2026. The company is also on track to initiate a Phase 2 study evaluating the combination in first-line GIST patients with exon 9 mutations. In parallel, an NDA submission for bezuclastinib in advanced systemic mastocytosis (AdvSM) remains planned for the first half of 2026.
Additionally, Cogent has established Expanded Access Programs (EAPs) in the U.S. for eligible patients with GIST or systemic mastocytosis, providing access to bezuclastinib alone or in combination with sunitinib.
Reference
Cogent Biosciences Announces Submission of New Drug Application for Bezuclastinib in Gastrointestinal Stromal Tumors (GIST), 01 April 2026, https://investors.cogentbio.com/news-releases/news-release-details/cogent-biosciences-announces-submission-new-drug-application-0
(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects with Gastrointestinal Stromal Tumors, ClinicalTrials.gov ID NCT05208047, https://clinicaltrials.gov/study/NCT05208047
About the Writer
Nikita Jha is a pharmacy graduate with expertise in clinical research, pharmacovigilance, and medical writing. In her words, she is passionate about translating complex scientific data into clear, accurate healthcare communications that advance drug safety and patient care.