(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
(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
This is an open-label, single arm, Phase 2 study evaluating the efficacy and safety of
 avapritinib (BLU-285) in patients with advanced systemic mastocytosis (AdvSM), including
 patients with aggressive SM (ASM), SM with associated hematologic neoplasm (SM-AHN), and mast
 cell leukemia (MCL)
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.