On Monday, the U.S. Food and Drug Administration (FDA) designated Cogent Biosciences, Inc.'s (NASDAQ:COGT) bezuclastinib, administered in combination with sunitinib, as a Breakthrough Therapy for patients diagnosed with gastrointestinal stromal tumors (GIST). This recognition reflects the promising efficacy demonstrated in clinical trials involving patients who had previously undergone therapy with Novartis AG’s (NYSE:NVS) Gleevac (imatinib). Sunitinib, the accompanying agent in the combination regimen, is marketed by Pfizer Inc. (NYSE:PFE) under the brand name Sutent.
The FDA's Breakthrough Therapy Designation is grounded in results from the PEAK trial. This study showed a pronounced and statistically significant improvement in progression-free survival (PFS), which is the primary endpoint in this context. Specifically, the risk of disease progression or death was halved when using the bezuclastinib plus sunitinib combination compared to standard treatment with sunitinib alone.
According to trial data, the median PFS for patients receiving the combination therapy was 16.5 months, notably longer than the 9.2 months observed among those treated only with sunitinib. Additionally, the tolerability profile for the combination regimen remained favorable, with no new safety concerns emerging beyond those already established for sunitinib monotherapy.
Earlier this month, the FDA agreed to include Cogent's New Drug Application (NDA) for the bezuclastinib plus sunitinib treatment under the FDA's Real-Time Oncology Review (RTOR) program. The RTOR program facilitates a streamlined review process, enabling the FDA to commence evaluation of clinical data components prior to submission of the complete NDA dossier, potentially accelerating regulatory decision timelines.
Cogent is planning to initiate the RTOR process promptly, anticipating that the full NDA submission will be completed by April 2026. In the first half of 2026, detailed results from the PEAK trial are expected to be presented at a major medical conference, providing the oncology community with comprehensive insight into the clinical benefits observed.
Moreover, Cogent has plans to launch a Phase 2 clinical trial by mid-2026 that will evaluate the bezuclastinib and sunitinib combination as a first-line treatment specifically for GIST patients exhibiting exon 9 mutations. These patients would either be treatment-naive or have recently started on imatinib therapy.
In related regulatory activity, Cogent Biosciences submitted an NDA in December 2025 for bezuclastinib in the indication of Non-Advanced Systemic Mastocytosis (SSM). This submission leverages clinical evidence from the SUMMIT pivotal trial and follows the awarding of Breakthrough Therapy Designation for bezuclastinib in patients with SSM as well as those with Non-Advanced Systemic Mastocytosis who previously received treatment with Sanofi SA's (NASDAQ:SNY) Ayvakit (avapritinib).
The introduction of bezuclastinib in combination with sunitinib represents a potentially meaningful advance in the management of GIST, particularly for patients who have progressed after imatinib therapy. By substantially extending progression-free survival without introducing new safety concerns, this regimen addresses an important unmet medical need.
Market reaction to the recent developments was positive, with COGT shares rising 1.87% to $37.35 as of the last check on Monday, based on Benzinga Pro data.
Major pharmaceutical players involved in drugs relevant to this treatment landscape include Novartis AG, Pfizer Inc., and Sanofi SA, each managing products integral to GIST and related disorders.