An open-label Phase 2 clinical study called Apex is currently evaluating the safety and efficacy of bezuclastinib (CGT9486) in patients with advanced systemic mastocytosis (SM), according to information published on clinicaltrials.gov.
Bezuclastinib is an investigational oral tyrosine kinase inhibitor. It specifically targets KIT D816V, the most common mutation driving advanced SM. Unlike currently approved therapies such as avapritinib and midostaurin, bezuclastinib remains experimental and is being developed for patients who may not tolerate or respond to existing treatments. It is taken orally in 28-day cycles.
Another Phase 2 clinical trial called SUMMIT is investigating the efficacy of bezuclastinib in patients with non-advanced forms of SM, such as indolent SM. The Apex trial, however, will enroll only patients with advanced SM, which includes the subtypes aggressive SM (ASM), SM with associated hematologic neoplasm (SM-AHN) and mast cell leukemia (MCL).
What is the difference between advanced and nonadvanced SM?
Nonadvanced SM comprises the indolent SM and smoldering SM subtypes. Advanced SM includes aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.
The trial is divided into two parts. Part I aims to identify a clinically active and tolerable dose of bezuclastinib, while Part II focuses on determining efficacy, using objective response rates, mutation burden reduction and changes in serum tryptase levels as key indicators.
Participants must have a confirmed advanced SM diagnosis and measurable disease per modified consensus criteria. Patients with significant cardiac conditions, active infections (HIV, hepatitis B/C) or recent cytoreductive therapies are excluded.
Read more about SM testing and diagnosis
The participants will be divided into two subgroups: the “Rollover Cohort,” composed of patients who previously benefited from bezuclastinib but now require additional treatment due to disease progression, and the “High-Risk Cohort” which includes individuals with SM-AHN and concurrent high-risk hematologic disorders such as myelodysplastic syndromes or chronic myelomonocytic leukemia (CMML-2).
The study will follow patients for 18 months. Researchers will monitor several outcome measures including objective response rate (ORR), pure pathologic response (PPR), mutation allele burden, mast cell infiltration, organ volume, progression-free survival (PFS) and overall survival (OS).
Previous evidence from other clinical trials suggest that bezuclastinib can reduce disease burden while maintaining a manageable safety profile. This trial is scheduled to complete in July 2026.
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