(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis

A Multi-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study of The Safety and Efficacy of CGT9486 in Subjects With Nonadvanced Systemic Mastocytosis

This is a multi-part, randomized, double-blind, placebo-controlled Phase 2 clinical study comparing the safety and efficacy of bezuclastinib (CGT9486) plus best supportive care (BSC) with placebo plus BSC in patients with nonadvanced systemic mastocytosis (NonAdvSM), including indolent systemic mastocytosis and smoldering systemic mastocytosis, whose symptoms are not adequately controlled by BSC. This study will be conducted in three parts. Patients in Parts 1a, 1b and 2 will receive bezuclastinib or placebo, and may roll over onto Part 3 to receive treatment with bezuclastinib.

Study Overview

• Status: Recruiting
• Conditions: Mastocytosis; Mastocytosis, Systemic; SSM; Mastocytosis, Indolent
• Intervention / Treatment: Drug: Placebo Tablets; Drug: Bezuclastinib Tablets (Formulation A); Drug: Bezuclastinib Tablets (Formulation B)

• Study Type: Interventional
• Enrollment (Estimated): 138
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hina Jolin, PharmD; Phone Number: +1 (617) 945-5576; Email: hina.jolin@cogentbio.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Royal Prince Alfred Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
• Belgium
  • Edegem, Belgium, 2650
    • Recruiting
    • Antwerp University Hospital (UZA)
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Recruiting
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 2R3
      • Recruiting
      • University of Alberta
  • Ontario
    • Toronto, Ontario, Canada, M5G 1E2
      • Recruiting
      • Toronto Allergy and Asthma Clinic
• Czechia
  • Praha 10, Czechia
    • Recruiting
    • Fakultní nemocnice Královské Vinohrady
• France
  • Paris, France, 75013
    • Recruiting
    • AP-HP- Hopital Pitie-Salpetriere
  • Toulouse, France, 31400
    • Recruiting
    • CHU de Toulouse - Hôpital Larrey
• Germany
  • Aachen, Germany, 52074
    • Recruiting
    • Universitaetsklinikum Aachen, AoeR
  • Berlin, Germany, 12203
    • Recruiting
    • Charité Universitätsmedizin Berlin
  • Mannheim, Germany, 68167
    • Recruiting
    • University Medical Centre Mannheim
• Greece
  • Athens, Greece
    • Recruiting
    • Attikon University General Hospital Athens
• Ireland
  • Dublin, Ireland, D08 NHY1
    • Recruiting
    • St. James's Hospital
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
  • Firenze, Italy
    • Recruiting
    • Azienda Ospedaliero-Universitaria Careggi
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione Irccs Policlinico San Matteo
  • Rome, Italy, 168
    • Recruiting
    • Policlinico Universitario Agostino Gemelli
• Netherlands
  • Groningen, Netherlands, 9713
    • Recruiting
    • University Medical Center Groningen
• Norway
  • Oslo, Norway, 0424
    • Recruiting
    • Oslo University Hospital
• Poland
  • Gdańsk, Poland
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario Ramón y Cajal
  • Toledo, Spain
    • Recruiting
    • Instituto de Estudios de Mastocitosis de Castilla La Mancha-Hospital Virgen del Valle
• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • One of a Kind Clinical Research Center
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • Modena Allergy and Asthma Clinical
  • Florida
    • Clearwater, Florida, United States, 33756
      • Recruiting
      • Innovative Research of West Florida
    • Hialeah, Florida, United States, 33016
      • Recruiting
      • Maya Research Center
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic - Jacksonville
    • Orange City, Florida, United States, 32763
      • Recruiting
      • Mid Florida Hematology and Oncology Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • RUSH University
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Recruiting
      • Walter Reed National Military Medical Center
    • Glenn Dale, Maryland, United States, 20769
      • Recruiting
      • Allervie Clinical Research
    • White Marsh, Maryland, United States, 21162
      • Recruiting
      • Chesapeake Research Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic- Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University at St. Louis
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Recruiting
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Raleigh, North Carolina, United States, 27705
      • Recruiting
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45221
      • Recruiting
      • University of Cincinnati
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Recruiting
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75231
      • Recruiting
      • AIR Care
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Diagnosed with 1 of the following diagnoses according to the 2016 World Health Organization (WHO) classification for systemic mastocytosis (SM):

   • Indolent systemic mastocytosis (ISM), including the bone marrow mastocytosis subvariant
   • Smoldering systemic mastocytosis (SSM)
2. Moderate-to-severe symptoms based on a disease-specific PRO and after establishing a stable regimen of at least 2 antimediator therapies over a 14-day eligibility period
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
4. For patients receiving corticosteroids, the dose must be ≤10 mg/day of prednisone or equivalent

Key Exclusion Criteria:

1. Diagnosed with any of the following WHO SM classifications: bone marrow mastocytosis, advanced systemic mastocytosis including SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia; or mast cell sarcoma
2. Diagnosed with mastocytosis of the skin without systemic involvement
3. Received prior treatment with any targeted KIT inhibitor with the exception of approved agents for the treatment of SM
4. Received prior cytoreductive therapy or investigational agent for <14 days or 5 half- lives of the drug and for cladribine, interferon alpha, pegylated interferon, or antibody therapy <28 days or 5 half-lives of the drug (whichever is longer), before starting screening assessments
5. Received radiotherapy or psoralen and ultraviolet A therapy <14 days before starting screening assessments
6. Received any hematopoietic growth factor support <14 days before starting screening assessments
7. History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
8. Need for treatment of corticosteroids at >10 mg/day of prednisone or equivalent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: (Part 2) Placebo + BSC	Drug: Placebo Tablets; Placebo will be administered orally, once daily continuously for 28-day cycles
Experimental: (Part 1a) Bezuclastinib Dose 1 + BSC	Drug: Bezuclastinib Tablets (Formulation A); Bezuclastinib will be administered orally, once daily continuously for 28-day cycles; Other Names: CGT9486; PLX9486
Experimental: (Part 1a) Bezuclastinib Dose 2 + BSC	Drug: Bezuclastinib Tablets (Formulation A); Bezuclastinib will be administered orally, once daily continuously for 28-day cycles; Other Names: CGT9486; PLX9486
Placebo Comparator: (Part 1a) Placebo + BSC	Drug: Placebo Tablets; Placebo will be administered orally, once daily continuously for 28-day cycles
Experimental: (Part 1b) Bezuclastinib Dose 1 + BSC	Drug: Bezuclastinib Tablets (Formulation B); Bezuclastinib will be administered orally, once daily continuously for 28-day cycles; Other Names: CGT9486; PLX9486
Experimental: (Part 1b) Bezuclastinib Dose 2 + BSC	Drug: Bezuclastinib Tablets (Formulation B); Bezuclastinib will be administered orally, once daily continuously for 28-day cycles; Other Names: CGT9486; PLX9486
Placebo Comparator: (Part 1b) Placebo + BSC	Drug: Placebo Tablets; Placebo will be administered orally, once daily continuously for 28-day cycles
Experimental: (Part 2) Bezuclastinib Selected Dose + BSC	Drug: Bezuclastinib Tablets (Formulation B); Bezuclastinib will be administered orally, once daily continuously for 28-day cycles; Other Names: CGT9486; PLX9486
Experimental: (Part 3) Bezuclastinib + BSC	Drug: Bezuclastinib Tablets (Formulation A); Bezuclastinib will be administered orally, once daily continuously for 28-day cycles; Other Names: CGT9486; PLX9486; Drug: Bezuclastinib Tablets (Formulation B); Bezuclastinib will be administered orally, once daily continuously for 28-day cycles; Other Names: CGT9486; PLX9486

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Determine recommended dose of bezuclastinib (CGT9486) in subjects with NonAdvSM	Selection of the recommended dose to be used in subsequent parts of the study.	3 months
Part 2: Efficacy of bezuclastinib at the selected dose versus placebo	Mean absolute change in a disease-specific patient reported outcome (PRO)	6 months
Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events	CTCAE v5	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change and percent change in patient reported outcome (PRO) measures		Up to 24 months
Change and percent change in serum tryptase		Up to 24 months
Change and percent change in bone marrow mast cells		Up to 24 months
Safety and tolerability of bezuclastinib as assessed by number of adverse events	CTCAE v5	Up to 24 months
Proportion of subjects who had at least 50% reduction in serum tryptase		Up to 24 months
Proportion of subjects who had at least 50% reduction in mast cell burden		Up to 24 months
Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction		Up to 24 months
Change and percent change in the levels of KIT D816V mutation allele burden		Up to 24 months
Assess the pharmacokinetics (PK) of bezuclastinib in subjects with NonAdvSM	Plasma concentrations of CGT9846	Up to 24 months
Change and percent change in the Mast Cell Quality of Life (MC-QOL) Score	Scale of 0-100, higher numbers represent more severe impairment to quality of life.	up to 24 months
Change and percent change in 12-item Short Form Health Survey (SF-12)	Scale of 0-100, higher numbers represent better symptom outcomes	up to 24 months
Change and percent change in EuroQol 5 Dimensions 5 Levels (EQ 5D-5L)	Scale of 0-100, higher numbers represent better symptom outcomes	up to 24 months
Determine responder rates of subjects treated with bezuclastinib at the selected dose	Response rate based on reduction in disease specific PRO	6 months

Collaborators and Investigators

• Sponsor: Cogent Biosciences, Inc.
• Investigators: Study Director: Rachael Easton, MD, PhD, Cogent Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2022
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: November 19, 2021
• First Submitted That Met QC Criteria: January 8, 2022
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Hypersensitivity; Immune System Diseases; Hematologic Diseases; ISM; CGT9486; Bezuclastinib; PLX9486; Systemic Mastocytosis; Immune Complex Diseases; D816V; KIT D816V; CGT; PLX; NonAdvSM; Nonadvanced Systemic Mastocytosis; Indolent Systemic Mastocytosis; Smoldering Systemic Mastocytosis
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Mast Cell Activation Disorders; Mastocytosis; Mastocytosis, Systemic
• Other Study ID Numbers: CGT9486-21-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No