Cogent Biosciences announces updated data from ongoing Phase 2 APEX trial

Cogent Biosciences announced updated clinical data from its ongoing Phase 2 APEX clinical trial evaluating the selective KIT D816V inhibitor bezuclastinib in patients with advanced systemic mastocytosis. APEX is a global, open-label, multi-center, two-part Phase 2 clinical trial in patients with AdvSM evaluating the safety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib. As of the data cutoff date of October 26, 2022, 16 patients had been treated in Part 1 at one of four dose levels. The median age of patients at study entry was 69 years. Patients were enrolled with the following sub-types: three patients with aggressive systemic mastocytosis, 12 patients with systemic mastocytosis with associated hematologic neo-plasm, and one patient with mast cell leukemia. Three patients had received prior avapritinib and midostaurin treatment. As of the cutoff date October 26, 2022, bezuclastinib was generally well-tolerated at all doses. The majority of adverse events were Grade 1/2 and occurred in no more than one patient. Importantly, there were no related cases of cognitive impairment and no reported intracranial bleeding events, which have been associated with other KIT inhibitors. Limited low-grade edema was observed, and analysis of platelet counts in bezuclastinib-treated patients showed no trend in platelet reduction at any dose. As of the cutoff date of October 26, 2022, 11 patients were evaluable for response per the modified IWG-MRT-ECNM criteria, and 12 patients were evaluable for response using pure pathological response criteria. Reported ORR per mIWG-MRT-ECNM criteria includes centrally adjudicated confirmed and unconfirmed CR, CRh, PR, and CI.