(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

Launched by COGENT BIOSCIENCES, INC. · Aug 6, 2021

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called bezuclastinib for patients with advanced systemic mastocytosis (AdvSM), a serious condition involving an overabundance of mast cells, which can cause various health issues. The trial includes patients diagnosed with specific forms of AdvSM, such as aggressive systemic mastocytosis, mast cell leukemia, and systemic mastocytosis with an associated hematologic neoplasm. To participate, patients must have measurable disease and acceptable health results from local lab tests. However, those with certain health issues or recent treatments may not be eligible.

Participants in the trial can expect to receive the study drug and will be monitored closely for their health and any side effects. The trial is currently recruiting patients aged 65 to 74, and it is open to all genders. This study aims to better understand how effective bezuclastinib is for treating these advanced forms of mastocytosis, providing hope for improved care options for patients facing these challenging conditions.

Gender

ALL

Eligibility criteria

• Key Inclusion Criteria for Main Study:
• • 1. Diagnosed with one of the following advanced mastocytosis diagnoses by Eligibility Committee
• • 1. Aggressive Systemic Mastocytosis (ASM)
• • 2. Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN)
• • 3. Mast Cell Leukemia (MCL)
• • 2. Measurable disease according to modified IWG-MRT-ECNM criteria. (A subset of patients inevaluble per mIWG-MRT-ECNM will be included in the study).
• • 3. ECOG (0 to 3)
• • 4. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits
• Key Exclusion Criteria for Main Study:
• • 1. Persistent toxicity from previous therapy for AdvSM that has not resolved to ≤ Grade 1
• • 2. Associated hematologic neoplasm requiring immediate antineoplastic therapy
• • 3. Clinically significant cardiac disease
• • 4. Known positivity for the FIP1L1 PDGFRA fusion. Patients with eosinophilia without detectable KIT D816V mutation must demonstrate lack of PDGFRA fusion mutation prior to enrollment
• • 5. Seropositive for human immunodeficiency virus (HIV) 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody
• • 6. History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
• • 7. Diagnosed with or treated for malignancy other than the disease under study within the prior 3 years before enrollment
• • 8. Received any cytoreductive therapy or any investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon, and any antibody therapy less than 28 days, before screening bone marrow biopsy
• • 9. Received hematopoietic growth factor support within 14 days before the first dose of study drug
• • 10. Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives, whichever is longer, before the first dose of study drug
• • 11. Need for treatment with high dose steroids
• Key Inclusion Criteria for Substudy Population:
• • Rollover Cohort
• • 1. Demonstrate AHN progression requiring immediate AHN-directed therapy while receiving bezuclastinib
• • 2. Demonstrated clinical benefit from bezuclastinib therapy
• • 3. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits
• • High-Risk Cohort
• • 1. Receiving or indicated for AHN-directed therapy.
• 2. Diagnosed with one of the following pathologic diagnoses of SM-AHN:
• • 1. Myelodysplastic syndrome (MDS) that is high- or very high-risk
• • 2. Accelerated phase myeloproliferative neoplasm (MPN)
• • 3. MDS with excessive blasts in bone marrow or peripheral blood
• • 4. Chronic myelomonocytic leukemia-2 (CMML-2)
• • 3. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits.
• Key Exclusion Criteria for Substudy Population:
• • 1. Diagnosis of Philadelphia chromosome-positive malignancy
• • 2. Diagnosis of acute myeloid leukemia (AML)
• • 3. Appropriate for allogenic hematopoietic stem cell transplantation
• • 4. Any contraindication to selected concomitant therapy
• • 5. Rollover Cohort: Have not demonstrated acceptable tolerability of previous bezuclastinib therapy
• • 6. High-Risk Cohort: Previously treated with investigational therapy for AdvSM
• • 7. High-Risk Cohort: Previously treated with cytoreductive therapy and discontinued due to treatment-related toxicity
• • 8. High-Risk Cohort: Received any cytoreductive therapy or any investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon, and any antibody therapy less than 28 days, before screening or archival bone marrow biopsy