Expanded Access Program (EAP) for Avapritinib in Patients With AdvSM
Expanded Access Program (EAP) for Avapritinib in Patients With AdvSM
This is a US, multicenter, open-label expanded access program designed to provide access to
 avapritinib in eligible patients with AdvSM until such time that avapritinib becomes
 available through other mechanisms, or the Sponsor chooses to discontinue the program.
Inclusion Criteria:

 1. Patients who are ≥ 15 years of age, or ≥ 12 years of age AND ≥ 35 kg.

 2. Patients must have a diagnosis of advanced systemic mastocytosis (AdvSM) or smoldering
 systemic mastocytosis (SSM). AdvSM includes the following:

 -  Aggressive systemic mastocytosis (ASM)

 -  Systemic mastocytosis with an associated hematological neoplasm of non-mast-cell
 lineage (SM-AHN)

 -  Mast cell leukemia (MCL)

 3. Patient or legal guardian, if permitted by local regulatory authorities, provides
 written informed consent.

 4. Patient is not eligible for an ongoing study of avapritinib or cannot access an
 ongoing study of avapritinib.

 Exclusion Criteria:

 1. Patient meets any of the following laboratory criteria:

 -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0 × upper
 limit of normal (ULN); no restriction if due to suspected liver infiltration by
 mast cells.

 -  Bilirubin > 1.5 × ULN (>3 x ULN in the case of Gilbert's disease); no restriction
 if due to suspected liver infiltration by mast cells or Gilbert's disease.

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

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

 2. Patient has a history of a cerebrovascular accident or transient ischemic attacks
 within 1 year before the first dose of avapritinib or any other known risks of
 intracranial bleeding.

 3. Patient has a known risk or recent history (12 months before the first dose of
 avapritinib) of intracranial bleeding (e.g., brain aneurysm, concomitant vitamin K
 antagonist use).

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

 5. Patient has clinically significant, uncontrolled cardiovascular disease, including
 Grade III or IV congestive heart failure according to the New York Heart Association
 classification; myocardial infarction or unstable angina within the previous 6 months;
 clinically significant, uncontrolled arrhythmias; or uncontrolled hypertension.

 6. Female patients who are unwilling, if not postmenopausal or surgically sterile, to
 abstain from sexual intercourse or employ highly effective contraception during the
 avapritinib administration period and for at least 30 days after the last dose of
 avapritinib. Men who are unwilling, if not surgically sterile, to abstain from sexual
 intercourse or employ highly effective contraception during the avapritinib
 administration period and for at least 90 days after the last dose of avapritinib.

 7. Women who are pregnant or breast feeding.

 8. Patient has had a major surgical procedure (minor surgical procedures such as central
 venous catheter placement, tumor needle biopsy, and feeding tube placement are not
 considered major surgical procedures) within 14 days prior to the first dose of
 avapritinib.

 9. Hypersensitivity to avapritinib or to any of the excipients.

 10. Patient is participating in another interventional study.