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Bezuclastinib treatment for advanced systemic mastocytosis

A Phase 2 Open-Label, Multicenter Clinical Study of the Safety, Efficacy, Pharmacokinetic, and Pharmacodynamic Profiles of CGT9486 as a Single Agent in Patients With Advanced Systemic Mastocytosis

Phase 2 Interventional Cogent Biosciences, Inc. · NCT04996875

This study is testing a new treatment called bezuclastinib to see if it can help people with advanced systemic mastocytosis feel better and manage their symptoms.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment140 (estimated)
Ages18 Years and up
SexAll
SponsorCogent Biosciences, Inc. Industry-sponsored
Drugs / interventionsbezuclastinib
Locations42 sites (Birmingham, Alabama and 41 other locations)
Trial IDNCT04996875 on ClinicalTrials.gov

What this trial studies

This open-label, two-part Phase 2 study investigates the efficacy of bezuclastinib in patients diagnosed with Advanced Systemic Mastocytosis (AdvSM), including Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL). The study aims to evaluate the treatment's impact on measurable disease as defined by modified IWG-MRT-ECNM criteria. Participants will be monitored for safety and efficacy throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with advanced forms of mastocytosis, specifically ASM, SM-AHN, or MCL, who meet the study's inclusion criteria.

Not a fit: Patients with persistent toxicity from previous therapies or those requiring immediate antineoplastic therapy for associated hematologic neoplasms may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from advanced systemic mastocytosis.

How similar studies have performed: While this approach is novel for treating advanced systemic mastocytosis, similar studies targeting hematologic malignancies have shown promising results.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Birmingham, Alabama and 41 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Systemic MastocytosisSM With an Associated Hematologic NeoplasmMast Cell LeukemiaAggressive Systemic MastocytosisMastocytosisSystemic MastocytosisAdvanced MastocytosisAggressive Mastocytosis
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.