A clinical trial assessing the efficacy of bezuclastinib in improving systemic mastocytosis (SM) symptoms in patients with non-advanced SM has shown promising results after 12 weeks, according to a recent presentation in the European Hematology Association 2024 Congress.
Under normal conditions, mast cells are immune system cells that release substances such as cytokines and heparin to create inflammation and fight infection. In SM, these cells have excessive and pathological activity and infiltrate tissues where they are not usually found, such as the gastrointestinal tract and the liver.
The excessive release of proinflammatory substances and mast cell infiltration cause symptoms that can seriously affect a patient’s quality of life. Common symptoms include fatigue, itching, skin redness, abdominal pain, nausea, diarrhea, gastroesophageal reflux and cognitive impairment.
Although there are available treatments for SM symptom control, some patients don’t respond adequately or experience severe adverse effects. Therefore, there is interest in developing more alternatives for patients with the condition.
Learn more about SM therapies
“Agents targeting KIT D816V are used to treat [advanced and non-advanced SM], but unmet need remains,” the authors wrote.
Bezuclastinib is an oral drug that inhibits the mutated KIT D816V pathway, thus treating SM at its root. The drug’s safety has already been established through a phase 1 clinical trial that determined 100mg to be the optimal dose.
The SUMMIT phase 2 clinical trial aims to assess bezuclastinib’s impact on SM symptoms through the Mastocytosis Symptom Severity Daily Diary (MS2D2), a tool that allows patients to report symptom severity on a scale of zero to 10. The tool divides symptoms into four domains: neurocognitive, digestive, skin and fatigue.
Results after 12 weeks of treatment show that the patients who received bezuclastinib improved in all symptoms compared to those who received a placebo. The authors observed a significant reduction in the extent of skin lesions and a substantial decrease in SM blood markers.
The trial will continue monitoring results, and more patients are currently being enrolled.
