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 mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults. (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 inhibitorTyrosine kinase inhibitor Targeted therapies designed to block the KIT D816V mutation that drives most cases of SM. Includes avapritinib, midostaurin and imatinib. 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 SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm.. 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 tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. and KIT D816V variant allele fraction (VAF) in nearly all patients. Furthermore, all patients had a significant reduction in bone marrow (BM) mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. 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 AdvSMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. patients today.”
