(Apex) CGT9486 in Patients With Advanced Systemic Mastocytosis

Sponsor

Cogent Biosciences, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04996875

Collaborator

(none)

140

Enrollment

Locations

Arm

45.7

Anticipated Duration (Months)

12.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Advanced Systemic Mastocytosis (AdvSM) SM With an Associated Hematologic Neoplasm (SM-AHN) Mast Cell Leukemia (MCL) Aggressive Systemic Mastocytosis (ASM)	Drug: CGT9486 tablets	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

There are two parts to this study. Part I will be Dose Confirmation and Part II will be Expansion.There are two parts to this study. Part I will be Dose Confirmation and Part II will be Expansion.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 9, 2021

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CGT9486	Drug: CGT9486 tablets CGT9486 is supplied as tablets to be taken orally with food and water, continuously in 28-day cycles. Other Names: PLX9486 bezuclastinib

Arm

Intervention/Treatment

Experimental: CGT9486

Drug: CGT9486 tablets

CGT9486 is supplied as tablets to be taken orally with food and water, continuously in 28-day cycles.

Other Names:

PLX9486

bezuclastinib

Outcome Measures

Primary Outcome Measures

Determine the optimal dose of CGT9486 by safety assessments and response criteria [18 months]
Overall Response Rate according to modified IWG-MRT-ECNM response criteria [18 months]

Secondary Outcome Measures

Safety of CGT9486 as assessed by incidence of adverse events (AEs) [18 months]
Incidence of AEs according to CTCAE version 5.0 or higher
Mutation allele burden [18 months]
Percentage change in KIT D816V
Serum Tryptase [18 months]
Percentage change in Serum Tryptase
Pharmacokinetic studies [18 months]
Percentage change in plasma concentrations of CGT9486
Change from baseline in histopathologic findings in blood and bone marrow [18 months]
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 [18 months]
Percentage
Change in Patient Global Impression of Severity (PGIS) scale [18 months]
0 -10 points (higher values represent worse symptom outcomes)
Change in Patient Global Impression of Change (PGIC) scale [18 months]
0 - 7 points (higher values represent better symptom outcomes)
Change in Mastocytosis Quality of Life Questionnaire (MC-QoL) [18 months]
0 - 100 (higher values represent better symptom outcomes)
Change in Mastocytosis Activity Score (MAS) [18 months]
0 - 252 (higher values represent worse symptom outcomes)
Duration of Response (DOR) [18 months]
Months
Time to Response (TTR) [18 months]
Months
Progression Free Survival (PFS) [18 Months]
Months
Overall Survival (OS) [18 months]
Months
Pure Pathologic Response (PPR) [18 months]
Months

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 before the first dose of study drug
Need for treatment with steroids

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	Stanford Cancer Institute	Stanford	California	United States	94305
3	Galiz Research	Hialeah	Florida	United States	33016
4	Rush University Medical Center	Chicago	Illinois	United States	60612
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	Columbia University Irving Medical Center	New York	New York	United States	10032
7	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44106
8	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
9	Huntsman Cancer Institute - University of Utah Health	Salt Lake City	Utah	United States	84112
10	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
11	Guys' and St. Thomas' NHS Foundation Trust - Guys' Hospital	London		United Kingdom	SE1 9RT