(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

Open to people ages 18 years and up

1. Diagnosed with 1 of the following advanced mastocytosis diagnoses by Eligibility Committee
   1. Aggressive Systemic Mastocytosis (ASM)
   2. Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN)
   3. Mast Cell Leukemia (MCL)
2. Measurable disease according to modified IWG-MRT-ECNM criteria. (A subset of patients inevaluble per mIWG-MRT-ECNM will be included in the study).
3. ECOG (0 to 3)
4. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits.

1. Persistent toxicity from previous therapy for Advanced Systemic Mastocytosis that has not resolved to ≤ Grade 1
2. Associated hematologic neoplasm requiring immediate antineoplastic therapy
3. Clinically significant cardiac disease
4. Known positivity for the FIP1L1 PDGFRA fusion. Patients with eosinophilia without detectable KIT D816V mutation must also lack the PDGFRA fusion mutation prior to enrollment
5. Seropositive for human immunodeficiency virus (HIV) 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody
6. History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
7. Diagnosed with or treated for malignancy other than the disease under study within the prior 3 years before enrollment
8. Received any cytoreductive therapy or any investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon, and any antibody therapy less than 28 days, before screening bone marrow biopsy

9. Received hematopoietic growth factor support within 14 days before the first dose of study drug

   10. Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives,

   whichever is longer, before the first dose of study drug.

   11. Need for treatment with high dose steroids.