Cogent Advances Bezuclastinib Toward NDA Submission With Positive APEX Results

Bezuclastinib delivered rapid, deep, and durable clinical responses in patients with advanced systemic mastocytosis (AdvSM), according to updated results from the registration-directed APEX trial (NCT04996875) presented at the 2026 European Hematology Association (EHA) Congress.

The findings strengthen Cogent Biosciences planned New Drug Application (NDA) submission to the U.S. Food and Drug Administration later this month.

The analysis included 81 patients treated with bezuclastinib 150 mg once daily across major AdvSM subtypes, including systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), aggressive systemic mastocytosis (ASM), and mast cell leukemia (MCL). Advanced systemic mastocytosis is a rare, life-threatening mast cell disorder driven in most cases by the KIT D816V mutation.

Efficacy Outcomes

Among 68 evaluable patients, the primary endpoint assessed by modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (mIWG-MRT-ECNM) criteria showed an objective response rate (ORR) of 65%, with 57% achieving complete remission (CR), complete remission with partial hematologic recovery (CRh), or partial remission (PR). Using pure pathological response (PPR) criteria, the ORR reached 81% across all 81 treated patients.

Biomarker reductions were substantial. Eighty-nine percent of patients achieved at least a 50% reduction in serum tryptase levels, while 89% experienced at least a 50% reduction in bone marrow mast cells or clearance of mast cell aggregates. Among evaluable patients, 91% achieved at least a 50% reduction in KIT D816V variant allele frequency. Approximately one-third of patients achieved undetectable KIT D816V mutation levels, suggesting meaningful modification of the underlying disease process.

Bezuclastinib also demonstrated broad improvements in disease pathology, including reductions in aberrant CD25 and CD30 expression, normalization of mast cell morphology and bone marrow cellularity, and improvements in myelofibrosis. Many of these effects were observed as early as eight weeks after treatment initiation.

Durability and Survival

Responses translated into durable disease control, with 12-month progression-free survival (PFS) and overall survival (OS) rates of 79% and 87%, respectively. Median PFS and OS had not yet been reached at the March 2026 data cutoff.

Safety Profile

Bezuclastinib continued to demonstrate a favorable safety and tolerability profile, with infrequent dose reductions or treatment discontinuations due to treatment-related adverse events (TRAEs). The most common TRAEs included hair color changes, neutropenia, altered taste, thrombocytopenia, and elevated liver transaminases. Most transaminase elevations were low grade, asymptomatic, and reversible.

Implications for AdvSM Treatment

Cogent President and CEO Andrew Robbins said results from both the APEX and SUMMIT programs reinforce the potential of selective KIT D816V inhibition to establish a new treatment standard across systemic mastocytosis.

Daniel J. DeAngelo, MD, PhD, of Dana-Farber Cancer Institute added that the combination of strong efficacy and favorable tolerability could make bezuclastinib an important new treatment option for patients with advanced disease.

Cogent expects to complete its NDA submission in June 2026. If approved, bezuclastinib could become a new treatment option for patients with systemic mastocytosis, with a commercial launch anticipated later this year. The company is also advancing the therapy in gastrointestinal stromal tumors (GIST).

Reference

Cogent Biosciences Announces Detailed Data from APEX Pivotal Trial of Bezuclastinib in Patients with Advanced Systemic Mastocytosis at the 2026 European Hematology Association (EHA) Congress – Cogent Biosciences, Inc.