(PIONEER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, Versus Placebo in Patients With Indolent Systemic Mastocytosis

Official Title

A 3-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate Safety and Efficacy of Avapritinib (BLU-285), a Selective KIT Mutation-Targeted Tyrosine Kinase Inhibitor, in Indolent and Smoldering Systemic Mastocytosis With Symptoms Inadequately Controlled With Standard Therapy

Summary:

This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of avapritinib + best supportive care (BSC) with placebo + BSC in patients with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by BSC. The study will be conducted in 3 parts. All patients will receive treatment with avapritinib during Part 3 including those rolling over from the placebo group.

Trial Description

Primary Outcome:

• Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM
• Part 2: Proportion of responders, defined as ≥30% reduction in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS)

• Part 2: Proportion of patients with a ≥50% reduction in serum tryptase
• Part 2: Proportion of patients with a ≥50% reduction in peripheral blood V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele fraction or undetectable for patients with detectable mutation at Baseline
• Part 2: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS)
• Part 2: Proportion of patients with a ≥50% reduction in bone marrow mast cells or no aggregates for patients with aggregates at Baseline
• Change in serum tryptase
• Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele burden in blood
• Change in bone marrow mast cells
• Change in best supportive care (BSC) concomitant medication usage
• Change in Mastocytosis Quality of Life Questionnaire (MC-QoL)
• Change in Patient's Global Impression of Symptom Severity (PGIS)
• Change in 12-item Short Form Health Survey (SF-12)
• Change in Patients' Global Impression of Change (PGIC)
• Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L)
• Safety of avapritinib as assessed by number of adverse events
• Part 1 and Part 2 only: Area Under Curve (0 to Tau) for avapritinib

View this trial on ClinicalTrials.gov