Bezuclastinib improves SM symptoms significantly in clinical trial 

The treatment showed no severe adverse effects.

A clinical trial demonstrated that bezuclastinib significantly improved symptoms and biomarkers of systemic mastocytosis (SM), according to an article recently published in cancernetwork.

Results of the Phase 2 SUMMIT trial showed that a 100 mg bezuclastinib dose led to a significant reduction in serum tryptase levels, with close to 90% of patients exhibiting a 50% decrease after the first month of treatment, study authors said. Serum tryptase is the most frequently used biomarker for diagnosis and tracking of disease progression. 

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.

With regard to symptom improvement, researchers observed significant changes in the MS2D2 Total Symptom Score, a patient-reported outcome-measure scale based on 11 symptoms intended to assess symptom severity in patients with nonadvanced SM.

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After 24 months of treatment, there was a mean reduction of 27 points in the MS2D2 score. Nearly a third of the patients included were able to discontinue their symptomatic medication. 

The SUMMIT trial is a multipart, randomized, double-blind, placebo-controlled Phase 2 clinical study that aims to determine the safety and efficacy of bezuclastinib in patients with nonadvanced SM. The study compared the effects of bezuclastinib in 18 patients with a similar number of patients using a placebo. 

The trial was preceded by a Phase 1 study that determined that 100mg once daily was an effective, safe and tolerable dose. Most of the included patients were women and had a median age of 52 years.

Additionally, the trial revealed improvements in patient quality of life as determined by the Mastocytosis Quality of Life Questionnaire (MC-QoL). Many patients evolved from moderate to mild disease. 

In concordance with previous studies, the authors observed no severe adverse effects during the trial. The most common adverse effects included nausea, diarrhea, taste disorders, hair color changes and neutropenia.

“At 12 weeks, with a data cutoff on Dec. 18, 2023, the safety and tolerability profile of bezuclastinib was encouraging, with most treatment-emergent adverse events (TEAEs) considered low grade and reversible without dose modification,” the authors said. 

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