- 89% ORR in TKI-therapy naïve patients; 73% ORR in all evaluable patients with 27-week median follow-up
- Rapid and deep responses seen including first confirmed CR at 20 weeks; 77% of patients with at least 2 cycles of treatment had complete clearance of bone marrow mast cell aggregates
- Favorable safety and tolerability profile with no related cognitive effects or reported intracranial bleeding events
- Cogent to host investor webcast Monday, December 12 at 8:00 a.m. ET
WALTHAM, Mass. and BOULDER, Colo., Dec. 11, 2022 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced positive updated clinical data from its ongoing Phase 2 APEX clinical trial evaluating the selective KIT D816V inhibitor bezuclastinib in patients with advanced systemic mastocytosis (AdvSM). The data are being presented in an oral presentation at the 64th American Society of Hematology (ASH) Annual Meeting in New Orleans, LA.
“Advanced systemic mastocytosis is a rare and life-threatening disease,” said Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and APEX clinical trial investigator. “Updated results from the APEX trial demonstrate rapid and deep responses with bezuclastinib while maintaining an impressive safety and tolerability profile.”
“We are very encouraged by the clinical profile that bezuclastinib has shown to date,” said Andrew Robbins, President and Chief Executive Officer at Cogent Biosciences. “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 AdvSM patients and non-advanced systemic mastocytosis patients.”
Updated Data from Ongoing Phase 2 APEX Clinical Trial 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 (50 mg BID, 100 mg BID, 200 mg BID or 400 mg QD). The median age of patients at study entry was 69 years (ranging from 33-87 years). Patients were enrolled with the following sub-types: three patients with aggressive systemic mastocytosis (ASM), 12 patients with systemic mastocytosis with associated hematologic neo-plasm (SM-AHN), and one patient with mast cell leukemia (MCL). Three patients had received prior avapritinib and midostaurin treatment.
Updated Safety Data 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. Grade 3 events reported as at least possibly related to bezuclastinib were neutropenia (2 patients), thrombocytopenia (1 patient), anemia (1 patient) and hypersensitivity/mediator flare (1 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.
Updated Clinical Activity Data 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 (PPR) criteria. Reported ORR per mIWG-MRT-ECNM criteria includes centrally adjudicated confirmed and unconfirmed CR, CRh, PR, and CI.
- 89% ORR in TKI therapy naïve patients, including 67% of patients achieving CR, CRh or PR, and 22% of patients achieving CR or CRh
- 73% ORR in all patients, regardless of prior treatment
- 75% ORR in all patients by PPR criteria, regardless of prior treatment
Additionally, results of key markers of clinical activity were reported from 16 patients.
- 14/16 patients achieved ≥ 50% reduction in serum tryptase levels by central assessment
- 85% median reduction in serum tryptase
- Eight of these patients achieved reduction to