Cogent Biosciences presents APEX pivotal data for bezuclastinib in AdvSM
Cogent Biosciences has presented detailed results from its registration-directed APEX trial of bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) at the 2026 European Hematology Association Congress in Stockholm, reporting a 65% objective response rate against the primary endpoint using modified International Working Group criteria.
The updated data, drawn from 68 evaluable patients in Part 2 of the trial with a cutoff of 31 March 2026, showed that 57% of patients achieved a complete response, complete response with haematological improvement, or partial response as best outcome. A secondary endpoint based on pure pathological response criteria, assessed across all 81 treated patients, produced an 81% ORR. Twelve-month progression-free survival was 79% and twelve-month overall survival was 87%, with median durations for both endpoints remaining immature at the data cutoff.
Mast cell burden and pathobiology
The trial also generated striking pathobiology data. Among evaluable patients, 91% achieved at least a 50% reduction in KIT D816V variant allele frequency, and 89% achieved at least a 50% reduction in bone marrow mast cells or clearance of aggregates. An equal proportion, 89%, achieved at least a 50% reduction in serum tryptase. Cogent additionally reported that approximately one-third of patients reached undetectable levels of KIT D816V variant allele frequency, a finding the company characterises as evidence of disease modification rather than symptom control alone.
Responses were observed as early as eight weeks. Additional pathobiology improvements included reversal of abnormal CD25 and CD30 expression, normalisation of mast cell morphology and bone marrow cellularity, and improvement in myelofibrosis.
On safety, bezuclastinib's most common treatment-related adverse events were hair colour change and neutropenia, both at 31%, altered taste at 28%, thrombocytopenia at 25%, and liver enzyme elevations at 21%. Transaminase elevations were predominantly low-grade and reversible; of two patients with Grade 3 elevations, one discontinued and one continued on a reduced dose.
Daniel J. DeAngelo, Chief of the Division of Leukaemia at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School, said: "Coupled with an impressive safety and tolerability profile minimising off-target toxicities that allows for long-term therapeutic dosing, bezuclastinib will become an important treatment option for patients with advanced SM."
Regulatory path and competitive context
Cogent said the APEX new drug application is on track for submission to the FDA in June 2026, with a commercial launch planned for later this year in both systemic mastocytosis and gastrointestinal stromal tumour (GIST) subject to approval. The company also has an active expanded access programme in place for eligible US patients ahead of that decision.
The AdvSM treatment landscape has been reshaped by the approval of avapritinib, a KIT/PDGFRA inhibitor marketed by Blueprint Medicines, which was the first targeted therapy approved in the indication. Bezuclastinib's selectivity for KIT D816V is positioned by Cogent as a potential differentiator, with the company arguing that a more targeted profile reduces off-target toxicity and supports chronic dosing. Blueprint Medicines is also developing its own next-generation compound in mastocytosis, meaning the competitive dynamic for market share in a rare but underserved population is likely to intensify around the time Cogent reaches the market. Analysts and clinicians will scrutinise head-to-head tolerability data and real-world durability as the defining factors in prescriber choice.