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. Before enrollment, the
   Study Steering Committee must confirm the diagnosis of AdvSM (based on Central
   Pathology Laboratory assessment of bone marrow).

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

   3. Patient must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of
   0 to 3.

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, must 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) > 480 msec.

   6. Patient has a known risk or recent history (12 months before the first dose of study
   drug) of intracranial bleeding (eg, brain aneurysm, concomitant vitamin K antagonist
   use).

   7. Platelet count < 50,000/μL (within 4 weeks of the first dose of study drug) or
   receiving platelet transfusion(s).

   8. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 x the upper
   limit of normal (ULN); no restriction if due to suspected liver infiltration by mast
   cells.

   9. Bilirubin >1.5 × ULN; no restriction if due to suspected liver infiltration by mast
   cells or Gilbert's disease. (In the case of Gilbert's disease, a direct bilirubin >2 ×
   ULN would be an exclusion.)

10. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 or creatinine > 1.5 ×
   ULN.

11. Patient has a primary brain malignancy or metastases to the brain.

12. Patient has a history of a seizure disorder (eg, epilepsy) or requirement for
   antiseizure medication.