Bezuclastinib demonstrated encouraging safety and effectiveness for treating nonadvanced systemic mastocytosis (SM), according to updated results from the Phase 2 Summit trial to be presented at the 2024 American Society of Hematology Annual Meeting and Exposition.
The results showed that the 100 mg dose reduced mast cell burden, alleviated debilitating symptoms and improved quality of life compared to placebo.
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.
Nonadvanced SM, a rare disease caused by abnormal mast cell accumulation, is driven in most cases by the KIT D816V mutation. This condition can significantly impair patients’ daily lives through symptoms such as skin lesions, fatigue and gastrointestinal issues.
Read more about SM treatment and care
Bezuclastinib, a targeted tyrosine kinase inhibitor, addresses this mutation while minimizing treatment-related side effects.
“In Part 1 (12 week assessment), treatment with 100 mg bezuclastinib resulted in favorable safety and tolerability, significant and deep reductions across all markers of mast cell burden,” the study’s authors said.
The Summit trial assessed patients over 12 weeks, comparing outcomes between those taking 100 mg bezuclastinib and those on placebo. Participants treated with the drug experienced a 49.1% reduction in scores of symptom severity, nearly double the improvement seen in the placebo group. Notable changes included reduced fatigue and skin symptoms, with an average improvement of over three points on a 10-point scale for the most severe symptoms.
Beyond symptom management, bezuclastinib led to substantial decreases in objective disease markers. A total of 94% of treated patients achieved a 50% reduction in serum tryptase, a key indicator of mast cell activity. Similarly, reductions in bone marrow mast cells and KIT D816V mutation levels were observed in nearly all participants. The results highlighted the drug’s potential to address the root cause of the disease effectively.
Safety data were also promising. Most treatment-related side effects, such as mild gastrointestinal symptoms or changes in hair color, were reversible and did not require dose adjustments. Importantly, no significant issues such as cognitive impairment or bleeding were reported.
For patients struggling with nonadvanced SM, the results offered hope for better disease control and improved quality of life. As the trial progresses to its next phase, researchers continue to evaluate the drug’s long-term safety and efficacy.
“The presentation will report on durability and safety/tolerability data beyond 12 weeks for those patients randomized to 100 mg in Part 1 and patients who crossed over from placebo in Part 1 to 100 mg in Part 3. Summit Part 2 is actively enrolling,” the Summit trial researchers said.
