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

NCT05186753 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CGT9486-21-202
• Study Type: interventional
• Target: 237
• Locations: 15 countries
• Sites: 57

Brief Summary

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. Additionally, a substudy of subjects will investigate the efficacy, safety, and tolerability of bezuclastinib in patients who are experiencing inadequate symptom control with avapritinib.

Conditions

SSM; Mastocytosis, Indolent; Mastocytosis, Systemic; Mastocytosis; ISM; BMM; Smoldering Systemic Mastocytosis; Bone Marrow Mastocytosis

Keywords

Systemic Mastocytosis; Immune Complex Diseases; Immune System Diseases; Hypersensitivity; Hematologic Diseases; NonAdvSM; D816V; KIT D816V; Bezuclastinib; CGT9486; CGT; PLX; Nonadvanced Systemic Mastocytosis; PLX9486; Indolent Systemic Mastocytosis; ISM; Smoldering Systemic Mastocytosis; BMM; Bone Marrow Mastocytosis; SSM

Outcome Measures

Primary Outcomes (3)

• 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 on the Mastocytosis Symptom Severity Daily Diary (MS2D2)

  24 Weeks

• Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events

  CTCAE v5

  Up to 5 years

Secondary Outcomes (14)

• Part 2: Proportion of subjects who had at least 50% reduction in serum tryptase

  24 weeks

• Part 2: Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction

  24 weeks

• Part 2: Determine responder rates of subjects treated with bezuclastinib at the selected dose versus placebo

  24 weeks

• Part 2: Proportion of subjects who had at least 50% reduction in mast cell burden

  24 weeks

• Parts 1 & 2: Safety and tolerability of bezuclastinib as assessed by number of adverse events

  Up to 24 weeks

Other Outcomes (1)

• Substudy: Efficacy of bezuclastinib at selected dose in subjects whose symptoms are not adequately controlled by avapritinib

  Up to 2 years

Study Arms (10)

(Part 1a) Bezuclastinib Dose 1 + BSC

EXPERIMENTAL

Drug: Bezuclastinib Tablets (Formulation A)

(Part 1a) Bezuclastinib Dose 2 + BSC

EXPERIMENTAL

Drug: Bezuclastinib Tablets (Formulation A)

(Part 1a) Placebo + BSC

PLACEBO COMPARATOR

Drug: Placebo Tablets

(Part 1b) Bezuclastinib Dose 1 + BSC

EXPERIMENTAL

Drug: Bezuclastinib Tablets (Formulation B)

(Part 1b) Bezuclastinib Dose 2 + BSC

EXPERIMENTAL

Drug: Bezuclastinib Tablets (Formulation B)

(Part 1b) Placebo + BSC

PLACEBO COMPARATOR

Drug: Placebo Tablets

(Part 2) Bezuclastinib Selected Dose + BSC

EXPERIMENTAL

Drug: Bezuclastinib Tablets (Formulation B)

(Part 2) Placebo + BSC

PLACEBO COMPARATOR

Drug: Placebo Tablets

(Part 3) Bezuclastinib + BSC

EXPERIMENTAL

Drug: Bezuclastinib Tablets (Formulation A); Drug: Bezuclastinib Tablets (Formulation B)

(Prior Therapy Sub-study) Bezuclastinib

EXPERIMENTAL

Drug: Bezuclastinib Tablets (Formulation B)

Interventions

Bezuclastinib Tablets (Formulation B) DRUG

Bezuclastinib will be administered orally, once daily continuously for 28-day cycles

Also known as: CGT9486, PLX9486

(Part 1b) Bezuclastinib Dose 1 + BSC; (Part 1b) Bezuclastinib Dose 2 + BSC; (Part 2) Bezuclastinib Selected Dose + BSC; (Part 3) Bezuclastinib + BSC; (Prior Therapy Sub-study) Bezuclastinib

Placebo Tablets DRUG

Placebo will be administered orally, once daily continuously for 28-day cycles

(Part 1a) Placebo + BSC; (Part 1b) Placebo + BSC; (Part 2) Placebo + BSC

Bezuclastinib Tablets (Formulation A) DRUG

Bezuclastinib will be administered orally, once daily continuously for 28-day cycles

Also known as: CGT9486, PLX9486

(Part 1a) Bezuclastinib Dose 1 + BSC; (Part 1a) Bezuclastinib Dose 2 + BSC; (Part 3) Bezuclastinib + BSC

Eligibility Criteria

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

You may qualify if:

• Diagnosed with 1 of the following diagnoses according to the 2016 World Health Organization (WHO) classification for systemic mastocytosis (SM):
• Indolent systemic mastocytosis (ISM),
• Bone marrow mastocytosis (BMM)
• Smoldering systemic mastocytosis (SSM)
• Moderate-to-severe symptoms based on a minimum total symptom scoew (TSS) of the Mastocytosis Activity Score (MAS) and after establishing a stable regimen of at least 2 antimediator therapies over a 14-day eligibility period
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
• For patients receiving corticosteroids, the dose must be ≤10 mg/day of prednisone or equivalent

You may not qualify if:

• Persistent toxicity from previous therapy for NonAdvSM that has not resolved to ≤ Grade 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
• Diagnosed with mastocytosis of the skin without systemic involvement
• Received prior treatment with any targeted KIT inhibitor with the exception of approved agents for the treatment of SM
• 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
• Received radiotherapy or psoralen and ultraviolet A therapy \<14 days before starting screening assessments
• Received any hematopoietic growth factor support \<14 days or 5 half lives of the drug before starting screening assessments
• History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
• Need for treatment of corticosteroids at \>10 mg/day of prednisone or equivalent
• Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives before the first dose of study drug

Sponsors & Collaborators

• Cogent Biosciences, Inc.: lead

Study Sites (57)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

One of a Kind Clinical Research Center

Scottsdale, Arizona, 85258, United States

Location

Modena Allergy and Asthma Clinical

La Jolla, California, 92037, United States

Location

Innovative Research of West Florida

Clearwater, Florida, 33756, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20814, United States

Location

Allervie Clinical Research

Glenn Dale, Maryland, 20769, United States

Location

Institute for Asthma and Allergy

Wheaton, Maryland, 20902, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University at St. Louis

St Louis, Missouri, 63110, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

Location

Duke University

Raleigh, North Carolina, 27705, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45221, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37235, United States

Location

AIR Care

Dallas, Texas, 75231, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Metrodora Institute of Technology

West Valley City, Utah, 84119, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Antwerp University Hospital (UZA)

Edegem, 2650, Belgium

Location

CHU Tivoli

La Louvière, Belgium

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

Location

St. Michael's Hospital

Toronto, Ontario, Canada

Location

Fakultni nemocnice Kralovske Vinohrady

Prague, Czechia

Location

AP-HP- Hopital Pitie-Salpetriere

Paris, 75013, France

Location

CHU de Toulouse - Hopital Larrey

Toulouse, 31400, France

Location

Universitaetsklinikum Aachen, AoeR

Aachen, 52074, Germany

Location

Charité Universitätsmedizin Berlin

Berlin, 12203, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, Germany

Location

University Medical Centre Mannheim

Mannheim, 68167, Germany

Location

Cork University Hospital

Cork, Ireland

Location

St. James's Hospital

Dublin, D08 NHY1, Ireland

Location

IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola

Bologna, 40138, Italy

Location

AOU Policlinico Rodolico San Marco

Catania, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

AUSL della Romagna-Ospedale S.Maria delle Croci

Ravenna, Italy

Location

University Medical Center Groningen

Groningen, 9713, Netherlands

Location

Erasmus Rotterdam

Rotterdam, Netherlands

Location

Oslo University Hospital

Oslo, 0424, Norway

Location

Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii

Gdansk, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 1 - Klinika Hematoonkologii i Transplantacji Szpiku

Lublin, Poland

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28046, Spain

Location

Instituto de Estudios de Mastocitosis de Castilla La Mancha-Hospital Virgen del Valle

Toledo, Spain

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

MeSH Terms

Conditions

Mastocytosis; Mastocytosis, Systemic; Immune Complex Diseases; Immune System Diseases; Hypersensitivity; Hematologic Diseases

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mast Cell Activation Disorders; Hemic and Lymphatic Diseases

Study Officials

• Rachael Easton, MD, PhD

  Cogent Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In Part 1a and 1b of the study, patients with NonAdvSM will be randomly assigned to 1 of 2 dose levels of bezuclastinib plus BSC, or to placebo plus BSC. Upon analysis of the Part 1 data, a dose will be selected for Part 2. In Part 2, patients with NonAdvSM will be randomly assigned to the selected dose of bezuclastinib plus BSC, or to placebo plus BSC. Patients who complete Part 1 or Part 2 may participate in Part 3 in which all patients will receive bezuclastinib plus BSC. Subjects participating in the substudy will receive open-label bezuclastinib plus BSC.

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: January 11, 2022
• Study Start: June 27, 2022
• Primary Completion: May 22, 2025
• Study Completion (Estimated): April 1, 2030
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

PL (2); DE (5); ES (4); CA (3); IT (5); NO (1); IE (2); AU (2); CZ (1); NL (2); BE (2); CH (1); GB (1); FR (2); US (24)