An open-label, 2-part phase 2 study investigating CGT9486 (bezuclastinib) for the treatment of patients with advanced systemic mastocytosis (SM), including patients with aggressive SM, SM with associated hematologic neoplasm, and mast cell leukemia, is now recruiting.
The study will enroll 120 eligible adult participants who will take bezuclastinib oral tablets for continuous 28-day cycles.
The study design will include 2 parts. Part 1, dose optimization, will examine clinically active and tolerable exposures of bezuclastinib in patients with advanced SM for 18 months. Phase 2, expansion, will analyze the efficacy of bezuclastinib as measured by the mIWG objective response rate for 18 months and will be conducted through 2 stages.
The primary objectives are to determine the optimal dose of CGT9486 by safety assessments as well as evaluate the response criteria and response rate according to modified International Working Group-Myeloproliferative Neoplasms Research and Treatment & European Competence Network on Mastocytosis (IWG-MRT-ECNM) response criteria.
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The researchers will also investigate the safety of CGT9486 as assessed by the incidence of adverse events, the effects of the study medication on mutation allele burden and serum tryptase, the pharmacokinetics of bezuclastinib in subjects with advanced SM, the change from baseline in histopathologic findings in blood and bone marrow and spleen and liver volume, change in Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) scales, as well as Mastocytosis Quality of Life Questionnaire (MC-QoL), Mastocytosis Activity Score (MAS) as current secondary outcome measures.
Other secondary outcome measures include the duration of response, time to response, progression-free survival, overall survival, and pure pathologic response.
The estimated primary completion date is expected to be January 2025, and the actual completion date is September 2025. The sponsor of this study is Cogent Biosciences, Inc.
(Apex) Bezuclastinib in patients with advanced systemic mastocytosis. ClinicalTrials.gov. August 9, 2021. Last updated May 3, 2023. Accessed May 11, 2023.