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(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

Primary Purpose

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

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
bezuclastinib
Sponsored by
Cogent Biosciences, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Systemic Mastocytosis (AdvSM) focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham (UAB) HospitalRecruiting
  • Mayo Clinic ArizonaRecruiting
  • City of Hope Comprehensive Cancer CenterRecruiting
  • UCLA Medical CenterRecruiting
  • Stanford Cancer InstituteRecruiting
  • Galiz Research
  • Winship Cancer Institute - Emory UniversityRecruiting
  • Rush University Medical CenterRecruiting
  • Dana-Farber Cancer InstituteRecruiting
  • Columbia University Irving Medical Center
  • Cleveland Clinic Taussig Cancer CenterRecruiting
  • MUSC Health University Medical CenterRecruiting
  • The University of Texas MD Anderson Cancer CenterRecruiting
  • Huntsman Cancer Institute - University of Utah HealthRecruiting
  • Nepean HospitalRecruiting
  • Gold Coast University HospitalRecruiting
  • Peter MacCallum Cancer CentreRecruiting
  • AKH Wien, UniversitatsklinikumRecruiting
  • CHU de LiegeRecruiting
  • University of Alberta HospitalRecruiting
  • St. Michael's Hospital - Unity Health TorontoRecruiting
  • Centre Hospitalier Universitaire (CHU) de PoitiersRecruiting
  • Centre Hospitalier Universitaire (CHU) de ToulouseRecruiting
  • University Hospital AachenRecruiting
  • Universitätsklinikum FreiburgRecruiting
  • IRCCS Azienda Ospedaliero Universitaria di BolognaRecruiting
  • University Medical Center GroningenRecruiting
  • Oslo University HospitalRecruiting
  • Hospital Universitario Vall d'HebronRecruiting
  • Institut Català d'Oncologia - Hospital Duran i ReynalsRecruiting
  • Hospital Universitario Ramón y CajalRecruiting
  • University College London Hospital - NHS Foundation TrustRecruiting
  • Guy's Hospital - NHS Foundation TrustRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

bezuclastinib

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Safety of CGT9486 as assessed by incidence of Adverse Events (AEs)
Incidence of AEs according to CTCAE version 5.0 or higher
To determine the effects of bezuclastinib on mutation allele burden.
Percentage change in KIT D816V
To determine the effects of bezuclastinib on serum tryptase.
Percentage change in Serum Tryptase
To assess the pharmacokinetics of bezuclastinib in subjects with AdvSM.
Percentage change in plasma concentrations of bezuclastinib
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
Change in spleen and liver volume by imaging
Percentage change
Change in Patient Global Impression of Severity (PGIS) scale
0 -10 points (higher values represent worse symptom outcomes)
Change in Patient Global Impression of Change (PGIC) scale
0 - 7 points (higher values represent better symptom outcomes)
Change in Mastocytosis Quality of Life Questionnaire (MC-QoL)
0 - 100 (higher values represent better symptom outcomes)
Change in Mastocytosis Activity Score (MAS)
0 - 252 (higher values represent worse symptom outcomes)
Duration of Response (DOR)
Months
Time to Response (TTR)
Months
Progression Free Survival (PFS)
Months
Overall Survival (OS)
Months
Pure Pathologic Response (PPR)
Months

Full Information

First Posted
July 22, 2021
Last Updated
October 24, 2023
Sponsor
Cogent Biosciences, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04996875
Brief Title
(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 9, 2021 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cogent Biosciences, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
There are two parts to this study, including Part I, Dose Optimization, and Part II Expansion. Part II will be separated into two stages.
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
bezuclastinib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
bezuclastinib
Other Intervention Name(s)
PLX9486, CGT9486
Intervention Description
Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.
Primary Outcome Measure Information:
Title
Part I: Identify clinically active and tolerable exposures of bezuclastinib in patients with AdvSM
Time Frame
18 months
Title
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
Secondary Outcome Measure Information:
Title
Safety of CGT9486 as assessed by incidence of Adverse Events (AEs)
Description
Incidence of AEs according to CTCAE version 5.0 or higher
Time Frame
18 months
Title
To determine the effects of bezuclastinib on mutation allele burden.
Description
Percentage change in KIT D816V
Time Frame
18 months
Title
To determine the effects of bezuclastinib on serum tryptase.
Description
Percentage change in Serum Tryptase
Time Frame
18 months
Title
To assess the pharmacokinetics of bezuclastinib in subjects with AdvSM.
Description
Percentage change in plasma concentrations of bezuclastinib
Time Frame
18 months
Title
Change from baseline in histopathologic findings in blood and bone marrow
Description
Percentage change in mast cell infiltration in the bone marrow and percentage change in eosinophilia and monocytosis in the blood
Time Frame
18 months
Title
Change in spleen and liver volume by imaging
Description
Percentage change
Time Frame
18 months
Title
Change in Patient Global Impression of Severity (PGIS) scale
Description
0 -10 points (higher values represent worse symptom outcomes)
Time Frame
18 months
Title
Change in Patient Global Impression of Change (PGIC) scale
Description
0 - 7 points (higher values represent better symptom outcomes)
Time Frame
18 months
Title
Change in Mastocytosis Quality of Life Questionnaire (MC-QoL)
Description
0 - 100 (higher values represent better symptom outcomes)
Time Frame
18 months
Title
Change in Mastocytosis Activity Score (MAS)
Description
0 - 252 (higher values represent worse symptom outcomes)
Time Frame
18 months
Title
Duration of Response (DOR)
Description
Months
Time Frame
18 months
Title
Time to Response (TTR)
Description
Months
Time Frame
18 months
Title
Progression Free Survival (PFS)
Description
Months
Time Frame
18 Months
Title
Overall Survival (OS)
Description
Months
Time Frame
18 months
Title
Pure Pathologic Response (PPR)
Description
Months
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Diagnosed with 1 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. Key Exclusion Criteria: Persistent toxicity from previous therapy for Advanced Systemic Mastocytosis 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 also lack the 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hina Jolin, PharmD
Phone
+1 (617) 945-5576
Email
ApexInfo@cogentbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rachael Easton, MD, Ph.D.
Organizational Affiliation
Cogent Biosciences, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham (UAB) Hospital
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Name
Mayo Clinic Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Individual Site Status
Recruiting
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Name
Stanford Cancer Institute
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Name
Galiz Research
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Individual Site Status
Withdrawn
Facility Name
Winship Cancer Institute - Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Withdrawn
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Name
MUSC Health University Medical Center
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Huntsman Cancer Institute - University of Utah Health
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Recruiting
Facility Name
Nepean Hospital
City
Kingswood
State/Province
New South Wales
ZIP/Postal Code
2747
Country
Australia
Individual Site Status
Recruiting
Facility Name
Gold Coast University Hospital
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Individual Site Status
Recruiting
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne N.
State/Province
Victoria
ZIP/Postal Code
3051
Country
Australia
Individual Site Status
Recruiting
Facility Name
AKH Wien, Universitatsklinikum
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Name
CHU de Liege
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Individual Site Status
Recruiting
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2G3
Country
Canada
Individual Site Status
Recruiting
Facility Name
St. Michael's Hospital - Unity Health Toronto
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire (CHU) de Poitiers
City
Poitiers
ZIP/Postal Code
86000
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire (CHU) de Toulouse
City
Toulouse
ZIP/Postal Code
31300
Country
France
Individual Site Status
Recruiting
Facility Name
University Hospital Aachen
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum Freiburg
City
Freiburg
ZIP/Postal Code
79104
Country
Germany
Individual Site Status
Recruiting
Facility Name
IRCCS Azienda Ospedaliero Universitaria di Bologna
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Individual Site Status
Recruiting
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Oslo University Hospital
City
Oslo
ZIP/Postal Code
0450
Country
Norway
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08740
Country
Spain
Individual Site Status
Recruiting
Facility Name
Institut Català d'Oncologia - Hospital Duran i Reynals
City
Barcelona
ZIP/Postal Code
08908
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Recruiting
Facility Name
University College London Hospital - NHS Foundation Trust
City
London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Guy's Hospital - NHS Foundation Trust
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

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