Results from the APEX clinical trial suggest that bezuclastinib is safe and effective in patients with advanced systemic mastocytosis (SM), Cogent Biosciences shared in a recent press release.
“Coupling rapid, deep, durable responses with the safety and tolerability profile demonstrated by bezuclastinib provides these patients with a new choice to fight their disease without compromising their quality of life,” said Andrew Robbins, president and chief executive officer at Cogent.
Bezuclastinib is an oral drug that works to block the CD117 protein in patients with the KIT D816V mutation. Previously, results from the SUMMIT trial have found that bezuclastinib is effective in patients with nonadvanced SMNonadvanced SM In these subtypes of SM, mast cells accumulate in the body but do not usually cause severe organ damage. Nonadvanced SM includes the subtypes indolent SM and smoldering SM., and the PEAK trial demonstrated its efficacy in those with gastrointestinal stromal tumor.
What is a KIT gene mutationKIT gene mutation Most SM cases are caused by the KIT D816V mutation. The KIT gene codes for a type of protein called a receptor tyrosine kinase, which signals mast cells to grow, divide and move.?
SM is usually caused by a sporadic mutation in the KIT gene, which codes for a protein called CD117 transmembrane tyrosine kinase. The protein is involved in the growth, survival and migration of mast cells. The most common KIT mutation associated with SM is the D816V mutation, which results in the amino acid aspartic acid being replaced by the amino acid valine in the protein chain
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The trial included 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 all received 150 milligrams of bezuclastinib daily. Of these, 57 had SM with an associated hematologic neoplasm, 11 had aggressive SMAggressive SM A subtype of advanced SM marked by a high mast cell burden that leads to organ damage. Aggressive SM accounts for less than 10% of SM cases. and 13 had mast cell leukemiaMast cell leukemia The most severe subtype of SM, caused by the rapid buildup of immature mast cells in the bone marrow and blood. Mast cell leukemia accounts for less than 5% of SM cases and has a poor prognosis..
The findings revealed that 89% of patients experienced at least a 50% reduction in levels of 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., a marker of mast cell activationMast cell activation Describes when mast cells release histamine and other mediators into the blood stream in response to an allergen or other trigger. This leads to symptoms like fatigue, rash and, in severe cases, anaphylaxis.. Similarly, 89% experienced a reduction of at least 50% in their bone marrow 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. level.
The study also found that in 91% of participants, the frequency of mast cells testing positive for the KIT D816V mutation was cut by at least half.
Over the study period, 14.8% of patients needed to reduce their dose, but no participants stopped taking bezuclastinib due to side effects. The most common events were changes in hair color, low levels of neutrophils (a type of white blood cell), changes in taste, low platelet levels and elevated liver enzymes.
“Cogent is preparing for multiple commercial launches in the second half of 2026,” the company shared.
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