Ensayos clínicos

Inclusion Criteria:

• Patients who are ≥ 18 years of age.
• Patient must have SM, confirmed by Central Pathology Review of BM biopsy, and ISM or SSM subtype, as confirmed by WHO diagnostic criteria. In Part 1 of the study, only patients with a diagnosis of ISM are eligible.
• Patient must have moderate-to-severe symptoms based on minimum mean TSS over the 14-day eligibility screening period for assessment of TSS and ≥ 1 symptom in skin or GI domains of the ISM-SAF at Baseline. Minimum TSS for eligibility is ≥ 28.
• Patient must have failed to achieve symptom control for 1 or more Baseline symptoms, as determined by the Investigator, with at least 2 of the following symptomatic therapies administered at optimal (approved) dose and for a minimum of 4 weeks (28 days) before starting the ISM-SAF for determination of eligibility: H1 blockers, H2 blockers, proton-pump inhibitors, leukotriene inhibitors, cromolyn sodium, corticosteroids, or omalizumab.
• The patient’s SM symptomatic therapies (e.g., H1 and H2 blockers) must be stable (same dose, no new medications for SM) for ≥ 14 days before starting the ISM-SAF for determination of eligibility.
• If the patient is receiving corticosteroids, the dose must be ≤ 20 mg/d prednisone or equivalent, and the dose must be stable for ≥ 14 days before starting the ISM-SAF for determination of eligibility.
• Patient must have an Eastern Cooperative Oncology Group Performance Status of 0 to 2.
• Patient must be able to give written informed consent.

Exclusion Criteria:

• Patient must not have received prior treatment with avapritinib.
• Patient must not have had any cytoreductive therapy including but not limited to masitinib and midostaurin, or investigational agent for < 14 days or 5 half-lives of the drug (whichever is longer), and for cladribine, interferon alpha, pegylated interferon, or antibody therapy < 28 days or 5 half-lives of the drug (whichever is longer), before starting the ISM-SAF for determination of eligibility.
• Patient must not have received radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before starting the ISM-SAF for determination of eligibility.
• Patient must not have received any hematopoietic growth factor < 14 days before starting the ISM-SAF for determination of eligibility.
• Patient must not require therapy with a concomitant medication that is a strong inhibitor, strong inducer, or moderate inducer of cytochrome P450 3A4 (CYP3A4).
• Patient must not have a QT interval corrected using Fridericia’s formula (QTcF) of > 480 msec.
• Patient must not have a history of a seizure disorder (e.g., epilepsy) or requires antiseizure medication.
• Patient must not have a history of a cerebrovascular accident or transient ischemic attacks within 12 months before the first dose of study drug.
• Patient must not have a known risk or recent history (12 months before the first dose of study drug) of intracranial bleeding (e.g., brain aneurysm).