Cogent Biosciences has reported updated results from its pivotal APEX trial showing that the investigational therapy bezuclastinib produced high response rates and substantial reductions in disease burden among people with advanced systemic mastocytosis (SM). The findings were presented at the 2026 European Hematology Association Congress in Stockholm.
The trial evaluated bezuclastinib in 81 individuals with advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. who received a daily 150 mg dose of the drug. Among 68 evaluable patients, the researchers observed a 65% objective response rate. Using a separate pathological response assessment, the objective response rate reached 81% across all treated patients.
Researchers also reported evidence that bezuclastinib reduced multiple markers of disease activity. Nearly nine in 10 patients achieved at least a 50% reduction in serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. levels, while a similar proportion experienced at least a 50% reduction in bone marrow mast cells or clearance of mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. aggregates. Among those evaluated for the KIT D816V mutation, 91% achieved at least a 50% reduction in how often the mutation appeared.
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The company said the treatment demonstrated rapid effects on disease biology, with improvements seen in mast cell morphology, bone marrow cellularity fibrosis and abnormal cellular markers.
“The results from the APEX trial demonstrate clear evidence of bezuclastinib’s rapid and deep clinical activity in patients with advanced systemic mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults.,” Dr. Daniel J. DeAngelo, chief of the Division of Leukemia at the Dana-Farber Cancer Institute said in a statement. “Coupled with an impressive safety and tolerability profile minimizing off-target toxicities that allows for long-term therapeutic dosing, bezuclastinib will become an important treatment option for patients with advanced SM.”
Bezuclastinib continued to show a manageable safety profile. The most commonly reported treatment-related adverse events included hair color changes, neutropenia (low levels of a type of white blood cell), altered taste, thrombocytopenia (low platelet levels) and elevations in liver enzymes. Most liver-related events were low grade, reversible and did not require treatment discontinuation.
Cogent said it remains on track to submit a New Drug Application for bezuclastinib to the Food and Drug Administration this month, potentially bringing the therapy one step closer to regulatory review and possible approval for use in people with advanced SM.
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