(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 and Smoldering Systemic Mastocytosis

Key Inclusion Criteria:

- 1. Patient must have systemic mastocytosis (SM), confirmed by Central Pathology Review
of bone marrow biopsy, and indolent SM (ISM) or smoldering (SSM) subtype, as confirmed
by WHO diagnostic criteria. In Part 1 of the study, only patients with a diagnosis of
ISM are eligible.

- 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 symptom control for 1 or more Baseline symptoms
measured by ISM-SAF.

- 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 must not have received prior treatment with avapritinib.

- 2. Patient must not have had any cytoreductive therapy including but not limited to
masitinib and midostaurin, or investigational agent, < 14 days, and for cladribine,
interferon alpha, pegylated interferon, or antibody therapy < 28 days.

- 3. Patient must not have received radiotherapy or psoralen and ultraviolet A (PUVA)
therapy < 14 days.

- 4. Patient must not have received any hematopoietic growth factor < 14 days.

- 5. Patient must not have a QT interval corrected using Fridericia's formula (QTcF) of
> 450 msec.