Patients with systemic mastocytosis (SM) showed promising overall response rates (ORR) to treatment with bezuclastinib, according to data from the APEX 2 trial investigating the clinical benefits of the treatment, Cogent Biosciences Inc. announced recently. Cogent developed bezuclastinib to treat SM.
What is SM?
Systemic mastocytosis (SM) is a rare hematological disease characterized by mast cells that are overactive and accumulate in different parts of the body such as the bone marrow, liver, spleen, gastrointestinal tract and lymph nodes.
The ORR was 52%, according to the modified International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Competence Network on Mastocytosis (ECNM) criteria, the company said. The ORR reached 88% when researchers applied the pure pathological response (PPR) criteria.
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“We are excited to share today the updated clinical data from APEX Part 1 studying bezuclastinib in patients with advanced systemic mastocytosis,” said Andrew Robbins, Cogent’s president and CEO, in a statement.
“These results show the enormous promise that a highly potent, highly selective, non-brain penetrant KIT inhibitor may provide to this patient population,” Robbins added. “We look forward to completing enrollment in APEX Part 2 and sharing the results from that study in mid-2025.”
Bezuclastinib is a selective tyrosine kinase inhibitor that is designed to inhibit the KIT D816V mutation and other mutations in KIT exon 17, the company said.
The Phase 2 open-label, multicenter APEX 2 study included 23 patients with SM and associated hematological neoplasm (SM-AHN) and two patients with advanced SM. A previous study, which included 31 patients, determined 150mg to be the optimal dose of bezuclastinib.
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The study’s primary endpoint was the ORR, a measure of the percentage of patients who exhibit a response to a treatment. The mean time required to achieve a response was estimated at two months; the duration of the response is still to be determined.
The secondary endpoints of the study consisted of biomarker changes. The authors observed a reduction in more than 50% of serum tryptase and KIT D816V variant allele fraction (VAF) in nearly all patients. Furthermore, all patients had a significant reduction in bone marrow (BM) mast cell burden.
The study showed similar safety and tolerability data as previous studies, with only mild to moderate adverse effects that reverse spontaneously with time, the company said.
“Bezuclastinib has the potential to transform the treatment landscape for people living with advanced systemic mastocytosis,” said Daniel J. DeAngelo, chief of the Division of Leukemia at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, in the company’s statement. “The impressive clinical data presented today from APEX Part 1 demonstrates a combination of rapid and deep clinical responses, with a safety profile that avoids several of the most concerning side effects for AdvSM patients today.”