Part one of Cogent Biosciences’ phase 2 Apex trial aiming to test the safety and efficacy of bezuclastinib in patients with systemic mastocytosis (SM) has been completed, according to a release recently published as part of a poster presentation planned for the 65th annual American Society of Haematology (ASH) meeting.
SM is characterized by pathological mast cell activity, which can lead to varied clinical manifestations, including gastrointestinal, neurologic and dermatological symptoms. Bezuclastinib is an experimental tyrosine kinase inhibitor (TKI) drug that works by stopping the molecular pathway unleashed by the KIT D816V.
The abnormal mast cell proliferation observed in patients with SM results from a gain-of-function mutation (D816V) observed in exon 17 of the KIT gene. There are several SM subtypes, of which aggressive SM associated with mast cell leukemia (MCL) is the most severe form.
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The Apex trial aims to test bezuclastinib in adults with aggressive SM. The doses to be used in the trial were established by the results of the Apex 1 trial, in which patients received different dosages to determine the optimal one. Part one of the trial has completed enrollment.
“In [part one], patients were randomized 1:1:1:1 to bezuclastinib 50mg BID, 100mg BID, 200mg BID or 400mg QD. Patients with a history of prior TKI therapy (e.g., avapritinib, midostaurin) are permitted in the trial. Data from [part one] informed dose selection for [part two] of the trial,” the authors stated.
Part one of the Apex trial included 33 patients who received either 50mg, 100mg, 200mg, or 400mg of the drug. The majority of the patients were men with a positive KITD816V.
“Patients enrolled in [part one] of the Apex trial are generally representative of the population of patients with AdvSM based on patient characteristics and markers of disease,” the authors wrote.
They added that part one includes a small subset of patients with prior use of TKIs. Safety, clinical activity, and clinical objective response for all patients in part one will be included during the poster presentation.
