(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

July 30, 2026 updated by: Cogent Biosciences, Inc.

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
140

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
Available

Available

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • New South Wales
      • Kingswood, New South Wales, Australia, 2747
        • Recruiting
        • Nepean Hospital
    • Queensland
      • Southport, Queensland, Australia, 4215
        • Recruiting
        • Gold Coast University Hospital
    • Victoria
      • Melbourne N., Victoria, Australia, 3051
        • Recruiting
        • Peter MacCallum Cancer Centre
  • Austria
      • Vienna, Austria, 1090
        • Active, not recruiting
        • AKH Wien, Universitatsklinikum
  • Belgium
      • Liège, Belgium, 4000
        • Withdrawn
        • CHU de Liège
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2G3
        • Recruiting
        • University of Alberta Hospital
    • Ontario
      • Toronto, Ontario, Canada, M5B 1W8
        • Recruiting
        • St. Michael's Hospital - Unity Health Toronto
  • France
      • Paris, France, 75015
        • Active, not recruiting
        • Necker-Enfants Malades Hospital
      • Poitiers, France, 86000
        • Active, not recruiting
        • Centre Hospitalier Universitaire (CHU) de Poitiers
      • Toulouse, France, 31300
        • Active, not recruiting
        • Centre hospitalier universitaire (CHU) de Toulouse
  • Germany
      • Aachen, Germany, 52074
        • Active, not recruiting
        • University Hospital Aachen
      • Freiburg im Breisgau, Germany, 79104
        • Active, not recruiting
        • Universitätsklinikum Freiburg
      • Lübeck, Germany, 23562
        • Withdrawn
        • Uksh Campus Lubeck
      • Mannheim, Germany, 68167
        • Active, not recruiting
        • Universitätsklinikum Mannheim
  • Italy
      • Bologna, Italy, 40138
        • Terminated
        • IRCCS Azienda Ospedaliero Universitaria di Bologna
      • Florence, Italy, 50134
        • Withdrawn
        • Azienda Ospedaliero Universitaria Careggi
      • Salerno, Italy, 84131
        • Active, not recruiting
        • AOU San Giovanni di Dio e Ruggi dAragonia
      • Verona, Italy, 37124
        • Withdrawn
        • Azienda Ospidaleira Universitaria Integrata Verona
  • Netherlands
      • Groningen, Netherlands, 9713
        • Active, not recruiting
        • University Medical Center Groningen
  • Norway
      • Oslo, Norway, 0450
        • Active, not recruiting
        • Oslo University Hospital
  • Poland
      • Lublin, Poland, 20-400
        • Active, not recruiting
        • Public University Hospital No. 1 in Lublin
  • Spain
      • Barcelona, Spain, 08740
        • Active, not recruiting
        • Hospital Universitario Vall d'Hebron
      • Barcelona, Spain, 08908
        • Active, not recruiting
        • Institut Català d'Oncologia - Hospital Duran i Reynals
      • Madrid, Spain, 28034
        • Active, not recruiting
        • Hospital Universitario Ramón y Cajal
  • Switzerland
      • Basel, Switzerland, 4031
        • Recruiting
        • Universitätsspital Basel
  • United Kingdom
      • Leeds, United Kingdom, LS9 7TF
        • Recruiting
        • Leeds Teaching Hospitals NHS Trust
      • London, United Kingdom, NW1 2BU
        • Recruiting
        • University College London Hospital - NHS Foundation Trust
    • London
      • London, London, United Kingdom, SE1 9RT
        • Recruiting
        • Guy's Hospital - NHS Foundation Trust
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Active, not recruiting
        • University of Alabama at Birmingham (UAB) Hospital
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Arizona
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Comprehensive Cancer Center
      • Los Angeles, California, United States, 90095
        • Recruiting
        • UCLA Medical Center
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford Cancer Institute
    • Florida
      • Hialeah, Florida, United States, 33016
        • Withdrawn
        • Galiz Research
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Winship Cancer Institute - Emory University
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Withdrawn
        • Rush University Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
    • New York
      • New York, New York, United States, 10032
        • Withdrawn
        • Columbia University Irving Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Active, not recruiting
        • Cleveland Clinic Taussig Cancer Center
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • MUSC Health University Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute - University of Utah Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: bezuclastinib
Drug: bezuclastinib
Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.
Other Names:
  • CGT9486
  • PLX9486

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Part I: Identify clinically active and tolerable exposures of bezuclastinib in patients with AdvSM
Time Frame: 18 months
18 months
Part II: - Determine efficacy of bezuclastinib as measured by mIWG Objective Response Rate (ORR) - Confirm the exposure-response relationship of bezuclastinib
Time Frame: 18 months
18 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
18 months
Duration of Response (DOR)
Time Frame: 18 months
Months
18 months
Time to Response (TTR)
Time Frame: 18 months
Months
18 months
Progression Free Survival (PFS)
Time Frame: 18 Months
Months
18 Months
Overall Survival (OS)
Time Frame: 18 months
Months
18 months
Pure Pathologic Response (PPR)
Time Frame: 18 months
Months
18 months
Change in spleen and liver volume by imaging
Time Frame: 18 months
Percentage change
18 months
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
18 months
To determine the effects of bezuclastinib on mutation allele burden.
Time Frame: 18 months
Percentage change in KIT D816V
18 months
To determine the effects of bezuclastinib on serum tryptase.
Time Frame: 18 months
Percentage change in Serum Tryptase
18 months
To assess the pharmacokinetics of bezuclastinib in subjects with AdvSM.
Time Frame: 18 months
Percentage change in plasma concentrations of bezuclastinib
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cogent Biosciences, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Rachael Easton, MD, Ph.D., Cogent Biosciences, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 9, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 19, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 22, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 9, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 31, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CGT9486-20-201
  • 2021-001010-10 (EudraCT Number)
  • 2024-511407-42-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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