Study of BLU-263 in Advanced Systemic Mastocytosis (AdvSM) and and Other KIT Altered Hematologic Malignancies

• Status: Not yet recruiting
• Trial end date: 2027-11-05
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this clinical trial is to evaluate BLU-263 in participants with Advanced Systemic Mastocytosis (AdvSM), SM-Associated hematologic neoplasm (SM-AHN), and other hematologic malignancies. The main questions it aims to answer are:

• Determine Recommended Dose of BLU-263 monotherapy for participants with AdvSM

• Safety and tolerability of BLU-263 monotherapy

• Efficacy of BLU-263 monotherapy in participants with AdvSM

• Determine Recommended Dose of BLU-263 in combination with azacitidine in participants with AdvSM

• Safety and tolerability of BLU-263 in combination with azacitidine

• Efficacy of BLU-263 in combination with azacitidine in participants with AdvSM

The estimated study duration for each participant will be approximately 4 years: 2 years of treatment followed by 2 years of follow-up. Participants may be required to attend monthly visits for the first six months, followed by quarterly visits for the remainder of the study.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Blueprint Medicines Corporation
• Treatments: Azacitidine

Criteria

Key Inclusion Criteria :

• Participant has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-3

• Participant must have a new Bone Marrow (BM) biopsy or may use archival tissue if taken within 56 days prior to C1D1 and participant must be willing to have follow-up BM Biopsies.

• Participants receiving antineoplastic therapy within the preceding 12 weeks must have discontinued therapy due to disease progression, refractory disease, lack of efficacy, or intolerance.

Arm 1 (Monotherapy): Participants must have one of the following AdvSM diagnoses, based on World Health Organization (WHO) diagnostic criteria.

Before enrollment, the Central Pathology Laboratory must confirm the diagnosis of AdvSM (based on Central Pathology Laboratory assessment of BM):

1. Aggressive SM (ASM).

2. SM-AHN which in the opinion of the investigator is not considered to be a candidate for Hypomethylating agent (HMA) monotherapy. Incidental indolent, low-grade lymphoid AHNs (eg, chronic lymphocytic leukemia) not requiring treatment are eligible.

3. Mast cell leukemia (MCL), including diagnoses with an AHN component, which does not require a C-finding.

4. Upon discussion with the sponsor, other relapsed or refractory, potentially BLU-263-responsive hematologic neoplasms (e.g., those with evidence of aberrant KIT) may be considered for enrollment.

Key Exclusion Criteria:

• Diagnosis of a Philadelphia chromosome positive malignancy

• Acute myeloid leukemia.

• If the patient is receiving corticosteroids, and the dose has not been stable for ≥7 days.

• Within the 14 days prior to enrollment, participant has received any antineoplastic therapy (including midostaurin, avapritinib and other tyrosine kinase inhibitors [TKIs]) or an investigational agent.

• Patient has received hydroxyurea within 7 days prior to the first dose of BLU-263.

• Participant received prior HMA therapy (e.g., azacitidine, decitabine) for the current diagnosis.

• Patient must not be eligible for allogenic hematopoietic stem cell transplantation.

• Patient received prior radiotherapy within 14 days of screening BM biopsy.

• Participant received any hematopoietic growth factor (except erythropoietin) within 14 days of screening BM biopsy, or requiring growth factors to maintain adequate neutrophil or platelet levels.

Those participants maintained on a chronic dose of erythropoietin, whose hemoglobin is stable, and dose of erythropoietin has not been changed in the prior 28 days are allowed on study.

-Participant received >1 prior selective KIT inhibitor (eg: avapritinib or PLX-9486 (bezuclastinib)).

Arm 1 (Monotherapy):

• MDS that is very high- or high-risk as defined by the International Prognostic Scoring System for Myelodysplastic Syndromes-Revised (IPSS-R).

• A myeloid AHN with ≥10% BM or peripheral blood blasts.

• Platelet count <50 x 10^9/L (within 4 weeks prior to the first dose of study drug) or receiving platelet transfusions or thrombopoietin receptor agonists (TPO-RA) within the prior 14 days.