Advanced Systemic Mastocytosis (AdvSM)Phase 2NCT04996875

(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

A Phase 2 study testing bezuclastinib in people with Advanced Systemic Mastocytosis (AdvSM) and SM With an Associated Hematologic Neoplasm (SM-AHN), run by Cogent Biosciences, Inc. at 42 sites in 14 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Systemic Mastocytosis (AdvSM), SM With an Associated Hematologic Neoplasm (SM-AHN), Mast Cell Leukemia (MCL)
What is being tested?: bezuclastinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 140 participants
Where: 42 sitesin 14 countries
Study dates: 9 Nov 2021to Jul 2027
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Diagnosed with one of the following advanced mastocytosis diagnoses by Eligibility Committee
Aggressive Systemic Mastocytosis (ASM)
Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN)
Mast Cell Leukemia (MCL)
Measurable disease according to modified IWG-MRT-ECNM criteria. (A subset of patients inevaluble per mIWG-MRT-ECNM will be included in the study).
ECOG (0 to 3)

Show all 19Show fewer

Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits
Rollover Cohort
Demonstrate AHN progression requiring immediate AHN-directed therapy while receiving bezuclastinib
Demonstrated clinical benefit from bezuclastinib therapy
Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits
High-Risk Cohort
Receiving or indicated for AHN-directed therapy.
Diagnosed with one of the following pathologic diagnoses of SM-AHN:
Myelodysplastic syndrome (MDS) that is high- or very high-risk
Accelerated phase myeloproliferative neoplasm (MPN)
MDS with excessive blasts in bone marrow or peripheral blood
Chronic myelomonocytic leukemia-2 (CMML-2)
Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits.

Who cannot join

Persistent toxicity from previous therapy for AdvSM that has not resolved to ≤ Grade 1
Associated hematologic neoplasm requiring immediate antineoplastic therapy
Clinically significant cardiac disease
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
Seropositive for human immunodeficiency virus (HIV) 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody
History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study

Show all 19Show fewer

Diagnosed with or treated for malignancy other than the disease under study within the prior 3 years before enrollment
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
Received hematopoietic growth factor support within 14 days before the first dose of study drug
Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives, whichever is longer, before the first dose of study drug
Need for treatment with high dose steroids
Diagnosis of Philadelphia chromosome-positive malignancy
Diagnosis of acute myeloid leukemia (AML)
Appropriate for allogenic hematopoietic stem cell transplantation
Any contraindication to selected concomitant therapy
Rollover Cohort: Have not demonstrated acceptable tolerability of previous bezuclastinib therapy
High-Risk Cohort: Previously treated with investigational therapy for AdvSM
High-Risk Cohort: Previously treated with cytoreductive therapy and discontinued due to treatment-related toxicity
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

Trial locations and contacts

42 sites in 14 countries. Contact the study team or a site near you to ask about taking part.

Cogent Biosciences, Inc. contact

617-945-5576

ApexInfo@cogentbio.com

Country

City, postcode or hospital

Sites recruiting now only

42 sites in 14 countries

United States14 sites, 9 recruiting

Winship Cancer Institute - Emory University
Atlanta, Georgia, 30322
Recruiting
University of Alabama at Birmingham (UAB) Hospital
Birmingham, Alabama, 35233
Active, not recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Recruiting
MUSC Health University Medical Center
Charleston, South Carolina, 29425
Recruiting
Rush University Medical Center
Chicago, Illinois, 60612
Withdrawn
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44106
Active, not recruiting
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Recruiting
Galiz Research
Hialeah, Florida, 33016
Withdrawn
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Recruiting
UCLA Medical Center
Los Angeles, California, 90095
Recruiting
Columbia University Irving Medical Center
New York, New York, 10032
Withdrawn
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Recruiting
Huntsman Cancer Institute - University of Utah Health
Salt Lake City, Utah, 84112
Recruiting
Stanford Cancer Institute
Stanford, California, 94305
Recruiting

Other trials in United States

Germany4 sites

University Hospital Aachen
Aachen, 52074
Active, not recruiting
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79104
Active, not recruiting
UKSH Campus Lubeck
Lübeck, 23562
Withdrawn
Universitätsklinikum Mannheim
Mannheim, 68167
Active, not recruiting

Other trials in Germany

Italy4 sites

IRCCS Azienda Ospedaliero Universitaria di Bologna
Bologna, 40138
Terminated
Azienda Ospedaliero Universitaria Careggi
Florence, 50134
Withdrawn
AOU San Giovanni di Dio e Ruggi dAragonia
Salerno, 84131
Active, not recruiting
Azienda Ospidaleira Universitaria Integrata Verona
Verona, 37124
Withdrawn

Other trials in Italy

Australia3 sites, 3 recruiting

Nepean Hospital
Kingswood, New South Wales, 2747
Recruiting
Peter MacCallum Cancer Centre
Melbourne N., Victoria, 3051
Recruiting
Gold Coast University Hospital
Southport, Queensland, 4215
Recruiting

Other trials in Australia

France3 sites

Necker-Enfants Malades Hospital
Paris, 75015
Active, not recruiting
Centre Hospitalier Universitaire (CHU) de Poitiers
Poitiers, 86000
Active, not recruiting
Centre Hospitalier Universitaire (CHU) de Toulouse
Toulouse, 31300
Active, not recruiting

Other trials in France

Spain3 sites

Hospital Universitario Vall d'Hebron
Barcelona, 08740
Active, not recruiting
Institut Català d'Oncologia - Hospital Duran i Reynals
Barcelona, 08908
Active, not recruiting
Hospital Universitario Ramón y Cajal
Madrid, 28034
Active, not recruiting

Other trials in Spain

United Kingdom3 sites, 3 recruiting

Leeds Teaching Hospitals NHS Trust
Leeds, LS9 7TF
Recruiting
University College London Hospital - NHS Foundation Trust
London, NW1 2BU
Recruiting
Guy's Hospital - NHS Foundation Trust
London, SE1 9RT
Recruiting

Other trials in United Kingdom

Canada2 sites, 2 recruiting

University of Alberta Hospital
Edmonton, Alberta, T6G 2G3
Recruiting
St. Michael's Hospital - Unity Health Toronto
Toronto, Ontario, M5B 1W8
Recruiting

Other trials in Canada

Austria1 site

AKH Wien, Universitatsklinikum
Vienna, 1090
Active, not recruiting

Other trials in Austria

Belgium1 site

CHU de Liege
Liège, 4000
Withdrawn

Other trials in Belgium

Netherlands1 site

University Medical Center Groningen
Groningen, 9713
Active, not recruiting

Other trials in Netherlands

Norway1 site

Oslo University Hospital
Oslo, 0450
Active, not recruiting

Other trials in Norway

Poland1 site

Public University Hospital No. 1 in Lublin
Lublin, 20-400
Active, not recruiting

Other trials in Poland

Switzerland1 site, 1 recruiting

Universitätsspital Basel
Basel, 4031
Recruiting

Other trials in Switzerland

About this study

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

Conditions: Advanced Systemic Mastocytosis (AdvSM), SM With an Associated Hematologic Neoplasm (SM-AHN), Mast Cell Leukemia (MCL), Aggressive Systemic Mastocytosis (ASM)
Being tested: bezuclastinib
Keywords: Mastocytosis, 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, Hypersensitivity, Hematologic Diseases, Leukemia, Myeloid Leukemia, Acute Myeloid Leukemia, SM with Associated Hematologic Neoplasm, AdvSM, ASM
Medical subject headings: Mastocytosis, Systemic, Leukemia, Mast-Cell, Mastocytosis, Hematologic Neoplasms, Soft Tissue Neoplasms, Neoplasms by Site, Skin Diseases, Immune Complex Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

bezuclastinibDrug
Also called CGT9486, PLX9486
Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.

Study groups in NCT04996875
Study group	Role	What they receive
bezuclastinib	Experimental	Not described Receives: Drug: bezuclastinib

What is being measured

The primary outcome is the main question the study is designed to answer.

Part I: Identify clinically active and tolerable exposures of bezuclastinib in patients with AdvSM
Measured: 18 months
Part II: - Determine efficacy of bezuclastinib as measured by mIWG Objective Response Rate (ORR) - Confirm the exposure-response relationship of bezuclastinib
Measured: 18 months

Secondary outcomes (11)

Pure Pathologic Response (PPR)
Months
Measured: 18 months
Safety of CGT9486 as assessed by incidence of Adverse Events (AEs)
Incidence of AEs according to CTCAE version 5.0 or higher
Measured: 18 months
To determine the effects of bezuclastinib on mutation allele burden.
Percentage change in KIT D816V
Measured: 18 months
To determine the effects of bezuclastinib on serum tryptase.
Percentage change in Serum Tryptase
Measured: 18 months
To assess the pharmacokinetics of bezuclastinib in subjects with AdvSM.
Percentage change in plasma concentrations of bezuclastinib
Measured: 18 months
Change from baseline in histopathologic findings in blood and bone marrow
Percentage change in mast cell infiltration in the bone marrow and percentage change in eosinophilia and monocytosis in the blood
Measured: 18 months
Change in spleen and liver volume by imaging
Percentage change
Measured: 18 months
Duration of Response (DOR)
Months
Measured: 18 months
Time to Response (TTR)
Months
Measured: 18 months
Progression Free Survival (PFS)
Months
Measured: 18 Months
Overall Survival (OS)
Months
Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Nov 2021Jul 2027

First posted9 Aug 2021
Study start9 Nov 2021
Primary completion19 Sep 2025
Study completionJul 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Advanced Systemic Mastocytosis (AdvSM)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
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.
Masking: None (open label)
Enrolment: 140 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04996875
Sponsor's protocol ID: CGT9486-20-201
Other IDs: 2024-511407-42-00, 2021-001010-10
Status last verified: Sep 2026
First submitted: 22 Jul 2021
Last updated: 15 Sep 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No
Expanded access: Available