FDA Accepts NDA for Bezuclastinib Combo in Gastrointestinal Stromal Tumors

The FDA has accepted a new drug application (NDA) for bezuclastinib plus sunitinib (Sutent) as treatment for patients with gastrointestinal stromal tumors who have received prior treatment with imatinib (Gleevec), according to a press release from the developer, Cogent Biosciences.¹ The FDA’s decision was made under the Real-Time Oncology Review (RTOR) program, and the developer expects to initiate the RTOR process with the completion of the NDA submission in April 2026.

Bezuclastinib plus sunitinib were evaluated as treatment for patients with gastrointestinal stromal tumors in the open-label, randomized phase 3 PEAK trial (NCT05208047). Results from PEAK were most recently shared in November 2025.²

The experimental combination yielded a median progression-free survival (PFS) of 16.5 months, demonstrating a statistically significant clinical benefit compared with sunitinib monotherapy, which yielded a median PFS of 9.2 months (HR, 0.50; 95% CI, 0.39-0.65). The overall response rate (ORR) in imatinib-resistant patients was 46% with bezuclastinib plus sunitinib vs 26% with sunitinib monotherapy. At the time of the reported analysis, overall survival data were immature.

Furthermore, no unique risks were observed with the bezuclastinib plus sunitinib combination compared with the known safety profile of sunitinib. The combination was generally well tolerated.

It was previously reported that the most common grade 3 or higher treatment-emergent adverse events (TEAEs) in the combination and monotherapy arms were hypertension (29.4% vs 27.4%, respectively), neutropenia (15.2% vs 15.4%), alanine transferase/aspartate transferase increased (10.8% vs 1.4%), anemia (9.3% vs 4.8%), and diarrhea (7.8% vs 7.2%). Notably, treatment was discontinued due to treatment-related AEs by 7.4% of the bezuclastinib plus sunitinib group vs 3.8% of the sunitinib monotherapy group.

The developers noted that more complete results from the PEAK trial are going to be shared at a major medical conference during the first half of 2026.

“This milestone reflects the FDA’s recognition of the significant unmet need facing patients with imatinib-resistant [gastrointestinal stromal tumors],” said Andrew Robbins, president and chief executive officer of Cogent Biosciences, in the press release.¹ “Based on positive results from the PEAK trial, the bezuclastinib combination has the potential to be the first new approval in this patient population in over 20 years. We look forward to the continued, close collaboration with the FDA as we advance bezuclastinib toward commercialization.”

PEAK had an estimated enrollment of 442 patients and consisted of 2 parts.³ The first part confirmed the dose of bezuclastinib and evaluated the potential for drug-drug interactions between bezuclastinib and sunitinib, and the second part compared the efficacy of bezuclastinib plus sunitinib vs sunitinib alone.

Treatment consisted of both bezuclastinib plus sunitinib at 37.5 mg once daily until study stopping rules were met.

Those enrolled were 18 years or older with histologically confirmed locally advanced, metastatic, and/or unresectable gastrointestinal stromal tumors. Patients also had documented disease progression on or intolerance to imatinib, at least 1 measurable lesion, an ECOG performance status from 0 to 2, and clinically acceptable local laboratory screening results. Those in part 1a of the trial were required to have received at least 1 prior line of therapy for gastrointestinal stromal tumors, and those in part 1b were required to have received treatment with at least 2 prior tyrosine kinase inhibitors. In part 2, patients were only permitted to have received prior treatment with imatinib.

A phase 2 trial evaluating the feasibility and benefit of bezuclastinib plus sunitinib as a first-line treatment for patients with gastrointestinal stromal tumors who have exon 9 mutations and are naïve to, or recently initiated treatment with, imatinib is expected to launch in the first half of 2026.

References

1. Cogent Biosciences to initiate new drug application (NDA) submission for bezuclastinib under real-time oncology review (RTOR). News release. Cogent Biosciences. January 20, 2026. Accessed January 21, 2026. https://tinyurl.com/34budv6y
2. Cogent Biosciences reports positive results from bezuclastinib PEAK phase 3 trial in gastrointestinal stromal tumors (GIST). News release. Cogent Biosciences. November 10, 2025. Accessed January 21, 2026. https://tinyurl.com/yurb8wx7
3. (Peak) A phase 3 randomized trial of CGT9486+sunitinib vs. sunitinib in subjects with gastrointestinal stromal tumors. ClinicalTrials.gov. Updated November 25, 2025. Accessed January 21, 2026. https://tinyurl.com/b3f93yj6