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 SM, and the PEAK trial demonstrated its efficacy in those with gastrointestinal stromal tumor.
What is a KIT gene mutation?
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
Read more about SM therapies
The trial included 81 individuals with advanced SM who all received 150 milligrams of bezuclastinib daily. Of these, 57 had SM with an associated hematologic neoplasm, 11 had aggressive SM and 13 had mast cell leukemia.
The findings revealed that 89% of patients experienced at least a 50% reduction in levels of tryptase, a marker of mast cell activation. Similarly, 89% experienced a reduction of at least 50% in their bone marrow mast cell 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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