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.

Reference

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.