Purpose

This is an open-label, two-part Phase 2 study investigating CGT9486 for the treatment of patients with Advanced Systemic Mastocytosis (AdvSM), including patients with Aggressive SM (ASM), SM with Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Intervention Model Description
There are two parts to this study, including Part I, Dose Optimization, and Part II Expansion. Part II is separated into two stages.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
bezuclastinib
  • Drug: bezuclastinib
    Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.
    Other names:
    • CGT9486
    • PLX9486

Recruiting Locations

University of Alabama at Birmingham (UAB) Hospital
Birmingham, Alabama 35233

More Details

Status
Recruiting
Sponsor
Cogent Biosciences, Inc.

Study Contact

Hina Jolin, PharmD
+1 (617) 945-5576
ApexInfo@cogentbio.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.