Multinational randomized phase 2 trial of avapritinib versus placebo in indolent systemic mastocytosis

Indolent systemic mastocytosis (ISM) is a clonal mast-cell disease driven by the KIT D816V mutation. The multinational randomized phase 2 PIONEER trial evaluated avapritinib (a D816V-mutated KIT inhibitor) in patients with moderate to severe ISM. Patients were randomized to avapritnib or placebo for 24 weeks. After week 24 all patients received avapritinib. Avapritinib was superior to placebo for primary end point total symptom score, and for secondary endpoints. Edema and increases in alkaline phosphatase were more common with avapritinib than placebo; there were few treatment discontinuations because of adverse events.