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(Apex) CGT9486 in Patients With Advanced Systemic Mastocytosis

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ClinicalTrials.gov Identifier: NCT04996875
Recruitment Status : Recruiting
First Posted : August 9, 2021
Last Update Posted : July 12, 2022
Information provided by (Responsible Party):
Cogent Biosciences, Inc.

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Advanced Systemic Mastocytosis (AdvSM) SM With an Associated Hematologic Neoplasm (SM-AHN) Mast Cell Leukemia (MCL) Aggressive Systemic Mastocytosis (ASM) Drug: CGT9486 tablets Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: There are two parts to this study. Part I will be Dose Confirmation and Part II will be Expansion.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 9, 2021
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : September 2025

Arm Intervention/treatment
Experimental: CGT9486 Drug: CGT9486 tablets
CGT9486 is supplied as tablets to be taken orally with food and water, continuously in 28-day cycles.
Other Names:
  • PLX9486
  • bezuclastinib

Primary Outcome Measures :
  1. Determine the optimal dose of CGT9486 by safety assessments and response criteria [ Time Frame: 18 months ]
  2. Overall Response Rate according to modified IWG-MRT-ECNM response criteria [ Time Frame: 18 months ]

Secondary Outcome Measures :
  1. Safety of CGT9486 as assessed by incidence of adverse events (AEs) [ Time Frame: 18 months ]
    Incidence of AEs according to CTCAE version 5.0 or higher

  2. Mutation allele burden [ Time Frame: 18 months ]
    Percentage change in KIT D816V

  3. Serum Tryptase [ Time Frame: 18 months ]
    Percentage change in Serum Tryptase

  4. Pharmacokinetic studies [ Time Frame: 18 months ]
    Percentage change in plasma concentrations of CGT9486

  5. Change from baseline in histopathologic findings in blood and bone marrow [ Time Frame: 18 months ]
    Percentage change in mast cell infiltration in the bone marrow and percentage change in eosinophilia and monocytosis in the blood

  6. Change in spleen and liver volume by imaging [ Time Frame: 18 months ]

  7. Change in Patient Global Impression of Severity (PGIS) scale [ Time Frame: 18 months ]
    0 -10 points (higher values represent worse symptom outcomes)

  8. Change in Patient Global Impression of Change (PGIC) scale [ Time Frame: 18 months ]
    0 - 7 points (higher values represent better symptom outcomes)

  9. Change in Mastocytosis Quality of Life Questionnaire (MC-QoL) [ Time Frame: 18 months ]
    0 - 100 (higher values represent better symptom outcomes)

  10. Change in Mastocytosis Activity Score (MAS) [ Time Frame: 18 months ]
    0 - 252 (higher values represent worse symptom outcomes)

  11. Duration of Response (DOR) [ Time Frame: 18 months ]

  12. Time to Response (TTR) [ Time Frame: 18 months ]

  13. Progression Free Survival (PFS) [ Time Frame: 18 Months ]

  14. Overall Survival (OS) [ Time Frame: 18 months ]

  15. Pure Pathologic Response (PPR) [ Time Frame: 18 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

  1. Diagnosed with 1 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:

  1. Persistent toxicity from previous therapy for Advanced Systemic Mastocytosis 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 also lack the 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 before the first dose of study drug
  11. Need for treatment with steroids

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04996875

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

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United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Stanford Cancer Institute Recruiting
Stanford, California, United States, 94305
United States, Florida
Galiz Research Recruiting
Hialeah, Florida, United States, 33016
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Columbia University Irving Medical Center Recruiting
New York, New York, United States, 10032
United States, Ohio
Cleveland Clinic Taussig Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute - University of Utah Health Recruiting
Salt Lake City, Utah, United States, 84112
Hospital Universitario Ramón y Cajal Recruiting
Madrid, Spain, 28034
United Kingdom
Guys' and St. Thomas' NHS Foundation Trust - Guys' Hospital Recruiting
London, United Kingdom, SE1 9RT
Sponsors and Collaborators
Cogent Biosciences, Inc.
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Study Director: Jessica Sachs, MD Cogent Biosciences, Inc.
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Responsible Party: Cogent Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT04996875    
Other Study ID Numbers: CGT9486-20-201
2021-001010-10 ( EudraCT Number )
First Posted: August 9, 2021    Key Record Dates
Last Update Posted: July 12, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cogent Biosciences, Inc.:
Systemic Mastocytosis
Advanced Mastocytosis
Aggressive Mastocytosis
Hematologic Neoplasms
Mast Cell
Mast Cell Leukemia
Soft Tissue Neoplasms
Neoplasms by site
Skin Diseases
Immune Complex Diseases
Immune System Diseases
Hematologic Diseases
Myeloid Leukemia
Acute Myeloid Leukemia
SM with Associated Hematologic Neoplasm
Additional relevant MeSH terms:
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Mastocytosis, Systemic
Hematologic Neoplasms
Leukemia, Mast-Cell
Neoplasms by Histologic Type
Behavioral Symptoms
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Skin Diseases
Immune Complex Diseases
Immune System Diseases
Neoplasms by Site
Hematologic Diseases
Leukemia, Myeloid, Acute
Leukemia, Myeloid