A new phase 1/2, open-label, 2-arm study (AZURE) will investigate the efficacy and safety of BLU-263 in patients with advanced systemic mastocytosis (SM) and other KIT-associated hematologic malignancies.

The trial is expected to start December 1, 2022, and is not yet recruiting.

Participants with advanced SM, including aggressive SM, SM-associated hematologic neoplasm of nonmast cell lineage (SM-AHN), and mast cell leukemia, will receive BLU-263 monotherapy (oral tablets). Participants with high-risk and very high-risk SM-AHN will receive BLU-263 (oral tablets) in combination with azacitidine (ONUREG®, intravenous infusion/subcutaneous injection).

The primary outcome measure for the dose escalation is the number of dose-limiting toxicities over 28 days for BLU-263 monotherapy and BLU-263 in combination with azacitidine. The primary outcome measures for the dose escalation and expansion include the pure pathological response rate for SM in selective KIT inhibitor-naïve participants, the number of participants with adverse events, and the number of participants with serious adverse events. Furthermore, the investigators have established 22 secondary outcome measures.

Read about SM clinical trials

To participate in the study, patients must have a Eastern Cooperative Oncology Group performance status of 0 to 3 and a new bone marrow biopsy. Archival tissue may be accepted in specific situations. Participants must be willing to have follow-up bone marrow biopsies, and those receiving antineoplastic therapy within the previous 12 weeks must have discontinued therapy.

Excluded from the study are patients diagnosed with a Philadelphia chromosome-positive malignancy or acute myeloid leukemia, as well as those receiving corticosteroids if the dose has not been stable for 7 or more days. Limitations are also applied to patients who have received any antineoplastic therapy or investigational agent, hydroxyurea, hypomethylating agents, radiotherapy, or any hematopoietic growth factor (except erythropoietin).

Additional inclusion and exclusion criteria are applied to those enrolled in the monotherapy group.

The AZURE study is sponsored by Blueprint Medicines Corporation. The estimated study completion date is November 5, 2027.

Reference

Study of BLU-263 in advanced systemic mastocytosis (AdvSM) and and other KIT altered hematologic malignancies (AZURE). ClinicalTrials.gov. November 8, 2022. Updated November 8, 2022. Accessed November 10, 2022.