Inclusion Criteria
1. Able to provide written informed consent.
2. Able and willing to commit to recommended EAP protocol assessments.
3. ≥18 years of age.
4. Able to swallow tablets.
5. For women of childbearing potential, confirmation of a negative serum pregnancy test
prior to dosing and agreement to the use of a highly effective method of contraception
during the treatment period and for 6 weeks after the last dose of bezuclastinib. A barrier
contraception method is also required for women using hormonal contraceptives that are
CYP3A4 substrates (see Section 4.5.2 and 4.5.3).
6. For male patients able to father a child, agreement to use effective barrier contraception
(ie, condoms) during the treatment period and for 6 weeks after the last dose of
bezuclastinib.
7. Calculated eGFR ≥ 30 mL/min/1.73m2 .
8. Not receiving adequate disease control on current therapy(ies).
Disease-Related Criteria
NonAdvanced SM
9. Diagnosed with BMM, ISM, or SSM according to the 2022 WHO Classification for SM
based on local assessment.
10. Patients who have been previously treated with avapritinib and/or have no comparable or
satisfactory alternative therapy.
11. Have clinically acceptable laboratory screening results (clinical chemistry, hematology)
within certain limits specified below:
a. Absolute neutrophil count ≥ 1000/μL
b. Platelets ≥ 100,000/μL
Bezuclastinib Cogent Biosciences, Inc.
Protocol CGT9486-IEAP-001 19 February 2025
Confidential 20
c. Hgb ≥ 10 g/dL
d. AST and ALT (≤ 2.5 × ULN)
e. Direct bilirubin ≤ 1.5 × ULN
Advanced SM
12. Diagnosed with ASM, SM-AHN, or MCL according to the 2022 WHO classification for
SM based on local assessment, including patients that have myeloid and non-myeloid
AHN (ie, lymphoid/plasma cell dyscrasias).
13. Patients who have been previously treated with avapritinib and/or midostaurin and/or
have no comparable or satisfactory alternative therapy.
14. Have clinically acceptable laboratory screening results (clinical chemistry, hematology)
within certain limits specified below:
a. Absolute neutrophil count > 500/μL
b. Platelet count ≥ 50,000/μL (prior to first dose)
c. AST and ALT ≤ 2.5 × ULN or ≤ 5 × ULN if there is liver involvement by AdvSM
d. Direct bilirubin ≤ 1.5 × ULN; if related to AdvSM may be ≤ 3 × ULN
 

Exclusion Criteria
1. Patients who are eligible for and/or enrolled in an on-going bezuclastinib clinical trial.
2. Patients who discontinued investigational use of bezuclastinib in previous clinical trials
due to toxicity or withdrawal of consent.
3. Known hypersensitivity to bezuclastinib.
4. Pregnant or currently breastfeeding.
5. Prior or ongoing clinically significant illness or medical or physical condition (eg, cardiac
disease) that, in the opinion of the treating physician or Sponsor, could affect the safety
of the patient, or compromise participation in expanded access.
6. Received prior cytoreductive therapy or investigational agent within 7 days or
5 half--lives of the drug (whichever is longer) before starting bezuclastinib or are
receiving or will require additional antineoplastic therapy for an associated hematologic
neoplasm.
7. History of clinically significant bleeding event within 30 days before the first dose or
receiving anticoagulation for treatment of DVT or pulmonary embolism (patients
receiving prophylactic anticoagulation for nonvalvular atrial fibrillation or prevention of
DVT are allowed).
8. Received strong CYP3A4 inhibitors/inducers within 14 days or 5 drug half-lives before
the first dose, whichever is longer, or the need to continue treatment with strong CYP3A4
inhibitors or inducers during treatment with investigational bezuclastinib.
9. Persistent toxicity from previous therapy for SM (either NonAdvSM, AdvSM or AHN)
that has not resolved to ≤ Grade 1