Cogent Biosciences announced an upcoming presentation of initial data from the phase 2 APEX trial on bezuclastinib for patients with advanced systemic mastocytosis (SM). The presentation, announced via news release, will occur at the European Hematology Association (EHA) Annual Congress on June 10, 2022.

“There is a significant unmet need for novel, safe, and effective treatment options for patients with [advanced SM],” the authors wrote. “Early insights into the safety and tolerability profile and biomarker data will further inform clinical development of bezuclastinib in [advanced SM].”

Bezuclastinib is a highly selective tyrosine kinase inhibitor that is administered orally in adult patients. It has potent activity against KIT D86V, a genetic driver of SM pathogenesis. Thus far in clinical trials, bezuclastinib has been administered to over 100 participants and has demonstrated a reduction in tumor burden along with an acceptable safety profile.

Read more about SM experimental therapies

The aim of the current open-label, 2-part, multicenter trial is to include approximately 140 adult patients with advanced SM who have organ damage. For part 1 of the trial, the patients will be randomized to receive 50, 100, or 200 mg of bezuclastinib twice per day or 400 mg once per day.

The main endpoint will be the overall response rate as assessed by a central response review committee, and the data from part 1 will be used to determine the optimal dosage of bezuclastinib for further study of safety and efficacy in part 2 of the trial.

Preliminary data on safety, pharmacokinetics, and pharmacodynamics from part 1 will be presented at the EHA Congress, including adverse events, serious adverse events, dose modification frequencies, changes in mast cells, and burden of KIT D81V mutations.


Cogent Biosciences announces presentation at European Hematology Association (EHA) Annual Congress. News release. Cogent Biosciences; May 12, 2022.

DeAngelo DJ, Pullarkat V, Piris-Villaespesa M, et al. A phase 2 study of bezuclastinib (CGT9486), a novel, highly selective, potent KIT D816V inhibitor, in adults with advanced systemic mastocytosis (APEX): methods, baseline data, and early insights. Poster being presented at: European Hematology Association (EHA) 2022 Congress; June 9-12, 2022; Vienna, Austria.