Positive updated data have been announced for Cogent Biosciences’ selective KIT D81V inhibitor bezuclastinib, a novel therapy for patients with advanced systemic mastocytosis (SM). The data were presented this month at the 64th American Society of Hematology (ASH) Annual Meeting.

“We are especially excited that a growing body of data supports bezuclastinib’s differentiated safety and tolerability profile enabling therapeutic exposures that could support key differentiation for both [advanced SM] patients and non-advanced systemic mastocytosis patients,” said Andrew Robbins, president and chief executive officer at Cogent Biosciences.

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The data come from the ongoing phase 2 APEX trial, a global, open-label, multicenter study to assess the safety and efficacy of bezuclastinib along with its pharmacokinetic and pharmacodynamic profiles. A total of 16 patients had been treated at 1 of 4 twice-daily dosages (50 mg, 100 mg, 200 mg, or 400 mg ) in Part 1 of the study as of October 26, 2022.

The therapy was generally well tolerated at all dose levels, and most adverse events were Grade 1/2. A few Grade 3 events were reported, including neutropenia, thrombocytopenia, anemia, and hypersensitivity/media flare, but there were no reports of cognitive impairment or intracranial bleeding, as have been reported with other KIT inhibitors.

In terms of clinical activity, an 89% objective response rate (ORR) was reported in TKI-therapy naïve patients, 73% ORR in all patients, and 75% ORR in all patients by pure pathologic response criteria. Significant reductions in serum tryptase levels and bone marrow mast cells were also observed.

As a result of these data, Cogent will continue enrolling patients in Part 1 of the study with the aim of determining a dose for Part 2. Cogent is also enrolling patients in the SUMMIT study of bezuclastinib for patients with nonadvanced SM.


Cogent Biosciences announces positive updated clinical data from ongoing phase 2 APEX trial evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM). News Release. Cogent Biosciences; December 11, 2022.