Actively Recruiting

Phase 2
Age: 18Years +
All Genders
ID04996875

A Phase 2 Open-Label Study of Bezuclastinib for Advanced Systemic Mastocytosis Evaluating Safety, Efficacy, and Pharmacology

Led by Cogent Biosciences, Inc. · Updated on 2026-05-05

140

Participants Needed

42

Research Sites

92 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are investigating CGT9486 (bezuclastinib) in a Phase 2 open-label study for adults with Advanced Systemic Mastocytosis (AdvSM), including Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL). This study aims to evaluate the drug's safety, efficacy, pharmacokinetics, and pharmacodynamics in these conditions. Participants receive bezuclastinib tablets taken orally in continuous 28-day cycles. The study has two parts conducted over 18 months each: Part I focuses on identifying active and tolerable doses, while Part II assesses treatment effectiveness by measuring the modified IWG Objective Response Rate (ORR) and confirms exposure-response relationships. During the study, participants will undergo evaluations including blood and bone marrow tests, imaging for spleen and liver size, and monitoring of mutation levels and serum tryptase. Researchers will track adverse events, duration and time to response, progression-free and overall survival. The total study duration includes these assessments over 18 months.

CONDITIONS

Brief Title

(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Adults aged 18 years or older
  • Diagnosed with Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN), or Mast Cell Leukemia (MCL) confirmed by Eligibility Committee
  • Measurable disease by modified IWG-MRT-ECNM criteria or included subset
  • ECOG performance status of 0 to 3
  • Clinically acceptable local laboratory screening results in clinical chemistry and hematology
  • For Substudy Population (Rollover or High-Risk Cohorts), additional specific diagnostic and therapy-related criteria apply
Not Eligible

You will not qualify if you...

  • Persistent toxicity from previous AdvSM therapy not resolved to Grade 1 or less
  • Associated hematologic neoplasm requiring immediate antineoplastic therapy
  • Clinically significant cardiac disease
  • Positive for FIP1L1 PDGFRA fusion or related mutations if KIT D816V mutation not detected
  • Positive serology for HIV 1 or 2, hepatitis B surface antigen, or hepatitis C antibody
  • Significant bleeding event within 30 days before first study drug dose or need for therapeutic anticoagulation
  • Recent diagnosis or treatment of malignancy other than AdvSM within past 3 years
  • Recent use of cytoreductive therapy or investigational agents within 14 to 28 days before screening
  • Recent hematopoietic growth factor support within 14 days before first study drug dose
  • Recent use of strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives
  • Need for treatment with high dose steroids
  • Substudy exclusions include Philadelphia chromosome-positive malignancy, acute myeloid leukemia, allogenic stem cell transplant eligibility, contraindications to therapy, and prior investigational or cytoreductive therapy toxicity

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - Up to 18 months

Participants take bezuclastinib tablets orally, continuously in 28-day cycles to treat advanced systemic mastocytosis.

Regular visits to monitor safety and efficacy during treatment

Trial Site Locations

Total: 42 locations

1

University of Alabama at Birmingham (UAB) Hospital

Birmingham, Alabama, United States, 35233

Active, Not Recruiting

2

Mayo Clinic Arizona

Phoenix, Arizona, United States, 85054

Actively Recruiting

3

City of Hope Comprehensive Cancer Center

Duarte, California, United States, 91010

Actively Recruiting

4

UCLA Medical Center

Los Angeles, California, United States, 90095

Actively Recruiting

5

Stanford Cancer Institute

Stanford, California, United States, 94305

Actively Recruiting

6

Galiz Research

Hialeah, Florida, United States, 33016

Withdrawn

7

Winship Cancer Institute - Emory University

Atlanta, Georgia, United States, 30322

Actively Recruiting

8

Rush University Medical Center

Chicago, Illinois, United States, 60612

Withdrawn

9

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Actively Recruiting

10

Columbia University Irving Medical Center

New York, New York, United States, 10032

Withdrawn

11

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States, 44106

Active, Not Recruiting

12

MUSC Health University Medical Center

Charleston, South Carolina, United States, 29425

Actively Recruiting

13

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Actively Recruiting

14

Huntsman Cancer Institute - University of Utah Health

Salt Lake City, Utah, United States, 84112

Actively Recruiting

15

Nepean Hospital

Kingswood, New South Wales, Australia, 2747

Actively Recruiting

16

Gold Coast University Hospital

Southport, Queensland, Australia, 4215

Actively Recruiting

17

Peter MacCallum Cancer Centre

Melbourne N., Victoria, Australia, 3051

Actively Recruiting

18

AKH Wien, Universitatsklinikum

Vienna, Austria, 1090

Active, Not Recruiting

19

CHU de Liege

Liège, Belgium, 4000

Withdrawn

20

University of Alberta Hospital

Edmonton, Alberta, Canada, T6G 2G3

Actively Recruiting

21

St. Michael's Hospital - Unity Health Toronto

Toronto, Ontario, Canada, M5B 1W8

Actively Recruiting

22

Necker-Enfants Malades Hospital

Paris, France, 75015

Active, Not Recruiting

23

Centre Hospitalier Universitaire (CHU) de Poitiers

Poitiers, France, 86000

Active, Not Recruiting

24

Centre Hospitalier Universitaire (CHU) de Toulouse

Toulouse, France, 31300

Active, Not Recruiting

25

University Hospital Aachen

Aachen, Germany, 52074

Active, Not Recruiting

26

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany, 79104

Active, Not Recruiting

27

UKSH Campus Lubeck

Lübeck, Germany, 23562

Active, Not Recruiting

28

Universitätsklinikum Mannheim

Mannheim, Germany, 68167

Active, Not Recruiting

29

IRCCS Azienda Ospedaliero Universitaria di Bologna

Bologna, Italy, 40138

Active, Not Recruiting

30

Azienda Ospedaliero Universitaria Careggi

Florence, Italy, 50134

Active, Not Recruiting

31

AOU San Giovanni di Dio e Ruggi dAragonia

Salerno, Italy, 84131

Active, Not Recruiting

32

Azienda Ospidaleira Universitaria Integrata Verona

Verona, Italy, 37124

Withdrawn

33

University Medical Center Groningen

Groningen, Netherlands, 9713

Active, Not Recruiting

34

Oslo University Hospital

Oslo, Norway, 0450

Active, Not Recruiting

35

Public University Hospital No. 1 in Lublin

Lublin, Poland, 20-400

Active, Not Recruiting

36

Hospital Universitario Vall d'Hebron

Barcelona, Spain, 08740

Active, Not Recruiting

37

Institut Català d'Oncologia - Hospital Duran i Reynals

Barcelona, Spain, 08908

Active, Not Recruiting

38

Hospital Universitario Ramón y Cajal

Madrid, Spain, 28034

Active, Not Recruiting

39

Universitätsspital Basel

Basel, Switzerland, 4031

Actively Recruiting

40

Guy's Hospital - NHS Foundation Trust

London, London, United Kingdom, SE1 9RT

Actively Recruiting

41

Leeds Teaching Hospitals NHS Trust

Leeds, United Kingdom, LS9 7TF

Actively Recruiting

42

University College London Hospital - NHS Foundation Trust

London, United Kingdom, NW1 2BU

Actively Recruiting

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Research Team

C

Cogent Biosciences, Inc.

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

Frequently Asked Questions

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