(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
(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
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.
Key Inclusion Criteria:

 -  1. Patient must have SM, confirmed by Central Pathology Review of BM biopsy, and
 central review of B- and C-findings by WHO diagnostic criteria.

 -  2. Patient must have moderate-to-severe symptoms based on minimum mean total symptom
 score (TSS) of the ISM Symptom Assessment Form (ISM-SAF) over the 14-day eligibility
 screening period.

 -  3. Patient must have failed to achieve adequate symptom control for 1 or more Baseline
 symptoms.

 -  4. For patients receiving corticosteroids, the dose must be ≤ 20 mg/d prednisone or
 equivalent, and the dose must be stable for ≥ 14 days.

 -  5. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
 (PS) of 0 to 2.

 Key Exclusion Criteria:

 -  1. Patient has been diagnosed with any of the following WHO SM subclassifications:
 cutaneous mastocytosis only, smoldering SM, SM with associated hematologic neoplasm,
 aggressive SM, mast cell leukemia, or mast cell sarcoma.

 -  2. Patient must not have received prior treatment with avapritinib.

 -  3. Patient must not have had any cytoreductive therapy including but not limited to
 masitinib and midostaurin, or investigational agent for < 14 days or 5 half-lives of
 the drug (whichever is longer), and for cladribine, interferon alpha, pegylated
 interferon, or antibody therapy < 28 days or 5 half-lives of the drug (whichever is
 longer), before beginning the 14-day ISM-SAF eligibility TSS assessment.

 -  4. Patient must not have received radiotherapy or psoralen and ultraviolet A (PUVA)
 therapy < 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.

 -  5. Patient must not have received any hematopoietic growth factor the preceding 14
 days before beginning the 14-day ISM-SAF eligibility TSS assessment.

 -  6. Patient must not have a QT interval corrected using Fridericia's formula (QTcF) of
 > 480 msec.