(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

NCT04996875 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: CGT9486-20-2012024-511407-42-002021-001010-10
• Study Type: interventional
• Target: 140
• Locations: 13 countries
• Sites: 39

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).

Conditions

Advanced Systemic Mastocytosis (AdvSM); SM With an Associated Hematologic Neoplasm (SM-AHN); Mast Cell Leukemia (MCL); Aggressive Systemic Mastocytosis (ASM)

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; SM-AHN; MCL; Neoplasm; D816V; KIT D816V; AML; bezuclastinib; CGT9486; CGT; PLX; Connective Tissue Neoplasms; Urticaria Pigmentosa; High-risk myelodysplastic syndrome; Chronic myelomonocytic leukemia; Myeloproliferative neoplasm; High-risk myeloid neoplasm; High-risk MDS; MPN; High-risk MPN; Accelerated phase MPN; CMML

Outcome Measures

Primary Outcomes (2)

• Part I: Identify clinically active and tolerable exposures of bezuclastinib in patients with AdvSM

  18 months

• Part II: - Determine efficacy of bezuclastinib as measured by mIWG Objective Response Rate (ORR) - Confirm the exposure-response relationship of bezuclastinib

  18 months

Secondary Outcomes (11)

• Pure Pathologic Response (PPR)

  18 months

• Safety of CGT9486 as assessed by incidence of Adverse Events (AEs)

  18 months

• To determine the effects of bezuclastinib on mutation allele burden.

  18 months

• To determine the effects of bezuclastinib on serum tryptase.

  18 months

• To assess the pharmacokinetics of bezuclastinib in subjects with AdvSM.

  18 months

Study Arms (1)

bezuclastinib

EXPERIMENTAL

Drug: bezuclastinib

Interventions

bezuclastinib DRUG

Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.

Also known as: CGT9486, PLX9486

bezuclastinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Cogent Biosciences, Inc.: lead

Study Sites (42)

University of Alabama at Birmingham (UAB) Hospital

Birmingham, Alabama, 35233, United States

ACTIVE NOT RECRUITING

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

UCLA Medical Center

Los Angeles, California, 90095, United States

RECRUITING

Stanford Cancer Institute

Stanford, California, 94305, United States

RECRUITING

Galiz Research

Hialeah, Florida, 33016, United States

WITHDRAWN

Winship Cancer Institute - Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Rush University Medical Center

Chicago, Illinois, 60612, United States

WITHDRAWN

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

WITHDRAWN

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44106, United States

ACTIVE NOT RECRUITING

MUSC Health University Medical Center

Charleston, South Carolina, 29425, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Huntsman Cancer Institute - University of Utah Health

Salt Lake City, Utah, 84112, United States

RECRUITING

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

RECRUITING

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne N., Victoria, 3051, Australia

RECRUITING

AKH Wien, Universitatsklinikum

Vienna, 1090, Austria

ACTIVE NOT RECRUITING

CHU de Liege

Liège, 4000, Belgium

WITHDRAWN

University of Alberta Hospital

Edmonton, Alberta, T6G 2G3, Canada

RECRUITING

St. Michael's Hospital - Unity Health Toronto

Toronto, Ontario, M5B 1W8, Canada

RECRUITING

Necker-Enfants Malades Hospital

Paris, 75015, France

ACTIVE NOT RECRUITING

Centre Hospitalier Universitaire (CHU) de Poitiers

Poitiers, 86000, France

ACTIVE NOT RECRUITING

Centre Hospitalier Universitaire (CHU) de Toulouse

Toulouse, 31300, France

ACTIVE NOT RECRUITING

University Hospital Aachen

Aachen, 52074, Germany

ACTIVE NOT RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79104, Germany

ACTIVE NOT RECRUITING

UKSH Campus Lubeck

Lübeck, 23562, Germany

ACTIVE NOT RECRUITING

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

ACTIVE NOT RECRUITING

IRCCS Azienda Ospedaliero Universitaria di Bologna

Bologna, 40138, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliero Universitaria Careggi

Florence, 50134, Italy

ACTIVE NOT RECRUITING

AOU San Giovanni di Dio e Ruggi dAragonia

Salerno, 84131, Italy

ACTIVE NOT RECRUITING

Azienda Ospidaleira Universitaria Integrata Verona

Verona, 37124, Italy

WITHDRAWN

University Medical Center Groningen

Groningen, 9713, Netherlands

ACTIVE NOT RECRUITING

Oslo University Hospital

Oslo, 0450, Norway

ACTIVE NOT RECRUITING

Public University Hospital No. 1 in Lublin

Lublin, 20-400, Poland

ACTIVE NOT RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08740, Spain

ACTIVE NOT RECRUITING

Institut Català d'Oncologia - Hospital Duran i Reynals

Barcelona, 08908, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

ACTIVE NOT RECRUITING

Universitätsspital Basel

Basel, 4031, Switzerland

RECRUITING

Guy's Hospital - NHS Foundation Trust

London, London, SE1 9RT, United Kingdom

RECRUITING

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

RECRUITING

University College London Hospital - NHS Foundation Trust

London, NW1 2BU, United Kingdom

RECRUITING

MeSH Terms

Conditions

Mastocytosis, Systemic; Leukemia, Mast-Cell; Mastocytosis; Hematologic Neoplasms; Soft Tissue Neoplasms; Neoplasms by Site; Skin Diseases; Immune Complex Diseases; Immune System Diseases; Hypersensitivity; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms; Neoplasms, Connective Tissue; Urticaria Pigmentosa; Leukemia, Myelomonocytic, Chronic; Myeloproliferative Disorders

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Mast Cell Activation Disorders; Hemic and Lymphatic Diseases; Skin and Connective Tissue Diseases; Connective Tissue Diseases; Mastocytosis, Cutaneous; Skin Neoplasms; Pigmentation Disorders; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rachael Easton, MD, Ph.D.

  Cogent Biosciences, Inc.

  STUDY DIRECTOR

Central Study Contacts

Cogent Biosciences, Inc.

CONTACT

617-945-5576; ApexInfo@cogentbio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: There are two parts to this study, including Part I, Dose Optimization, and Part II Expansion. Part II is separated into two stages.

Study Record Dates

• First Submitted: July 22, 2021
• First Posted: August 9, 2021
• Study Start: November 9, 2021
• Primary Completion: September 19, 2025
• Study Completion (Estimated): July 1, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); CH (1); IT (4); ES (3); GB (3); CA (2); FR (3); BE (1); DE (4); NL (1); PL (1); NO (1); US (14)