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

Key Inclusion Criteria:

1. Patient must have a diagnosis of aggressive systemic mastocytosis (ASM), systemic
mastocytosis with an associated hematologic neoplasm (SM-AHN) or mast cell leukemia
(MCL) based on World Health Organization diagnostic criteria.

2. Patient must have at least 1 of the measurable C-finding per IWG-MRT-ECNM criteria
indicative of organ damage, attributed to SM and evaluable for response assessment
unless diagnosis is MCL, which does not require a C-finding.

3. Patient must have a serum tryptase ≥ 20 ng/mL.

Key Exclusion Criteria:

1. Patient has received prior treatment with avapritinib.

2. Patient has received any cytoreductive therapy (including midostaurin and other TKIs,
hydroxyurea, azacitidine) or an investigational agent less than 14 days, and for
cladribine, interferon alpha, pegylated interferon and any antibody therapy (eg,
brentuximab vedotin) less than 28 days before obtaining screening BM biopsy for this
study.

3. Patient has eosinophilia and known positivity for the FIP1L1 PGDFRA fusion, unless the
patient has demonstrated relapse or PD on prior imatinib therapy. Patients with
eosinophilia (> 1.5 × 10^9/L), who do not have a detectable KIT D816 mutation, should
be tested for a PDGFRA fusion mutation by fluorescence in situ hybridization (FISH) or
polymerase chain reaction (PCR).

4. Patient has history of another primary malignancy that has been diagnosed or required
therapy within 3 years before the first dose of study drug. The following are exempt
from the 3-year limit: completely resected basal cell and squamous cell skin cancer,
curatively treated localized prostate cancer, and completely resected carcinoma in
situ of any site.

5. Patient has a QT interval corrected using Fridericia's formula (QTcF) > 450 msec.