SSMPhase 2NCT05186753

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

A Phase 2 study testing Bezuclastinib Tablets (Formulation A) and Bezuclastinib Tablets (Formulation B) in people with SSM and Mastocytosis, Indolent, run by Cogent Biosciences, Inc. at 57 sites in 15 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: SSM, Mastocytosis, Indolent, Mastocytosis, Systemic
What is being tested?: Bezuclastinib Tablets (Formulation A) and Bezuclastinib Tablets (Formulation B)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 237 participants
Where: 57 sitesin 15 countries
Study dates: 27 Jun 2022to Jan 2030
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 10Show fewer

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

Trial locations and contacts

57 sites in 15 countries.

Country

City, postcode or hospital

57 sites in 15 countries

United States24 sites

University of Michigan
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30322
Walter Reed National Military Medical Center
Bethesda, Maryland, 20814
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Rush University
Chicago, Illinois, 60612
University of Cincinnati
Cincinnati, Ohio, 45221
Innovative Research of West Florida
Clearwater, Florida, 33756
The Ohio State University
Columbus, Ohio, 43210
AIR Care
Dallas, Texas, 75231
Allervie Clinical Research
Glenn Dale, Maryland, 20769
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
Modena Allergy and Asthma Clinical
La Jolla, California, 92037
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03766
Vanderbilt University Medical Center
Nashville, Tennessee, 37235
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Duke University
Raleigh, North Carolina, 27705
One of a Kind Clinical Research Center
Scottsdale, Arizona, 85258
Washington University at St. Louis
St Louis, Missouri, 63110
University of South Florida
Tampa, Florida, 33612
Metrodora Institute of Technology
West Valley City, Utah, 84119
Institute for Asthma and Allergy
Wheaton, Maryland, 20902

Other trials in United States

Germany5 sites

Universitaetsklinikum Aachen, AoeR
Aachen, 52074
Charité Universitätsmedizin Berlin
Berlin, 12203
Universitaetsklinikum Hamburg-Eppendorf
Hamburg
Universitätsklinikum Schleswig-Holstein
Kiel
University Medical Centre Mannheim
Mannheim, 68167

Other trials in Germany

Italy5 sites

IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
Bologna, 40138
AOU Policlinico Rodolico San Marco
Catania
Azienda Ospedaliero-Universitaria Careggi
Florence
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
AUSL della Romagna-Ospedale S.Maria delle Croci
Ravenna

Other trials in Italy

Spain4 sites

Hospital Universitario Vall d'Hebron
Barcelona, 08035
Institut Catala d'Oncologia - L'Hospitalet
Barcelona
Hospital Universitario Ramon y Cajal
Madrid, 28046
Instituto de Estudios de Mastocitosis de Castilla La Mancha-Hospital Virgen del Valle
Toledo

Other trials in Spain

Canada3 sites

Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
University of Alberta
Edmonton, Alberta, T6G 2R3
St. Michael's Hospital
Toronto, Ontario

Other trials in Canada

Australia2 sites

Royal Adelaide Hospital
Adelaide, South Australia, 5000
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050

Other trials in Australia

Belgium2 sites

Antwerp University Hospital (UZA)
Edegem, 2650
CHU Tivoli
La Louvière

Other trials in Belgium

France2 sites

AP-HP- Hopital Pitie-Salpetriere
Paris, 75013
CHU de Toulouse - Hopital Larrey
Toulouse, 31400

Other trials in France

Ireland2 sites

Cork University Hospital
Cork
St. James's Hospital
Dublin, D08 NHY1

Other trials in Ireland

Netherlands2 sites

University Medical Center Groningen
Groningen, 9713
Erasmus Rotterdam
Rotterdam

Other trials in Netherlands

Poland2 sites

Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
Gdansk
Samodzielny Publiczny Szpital Kliniczny Nr 1 - Klinika Hematoonkologii i Transplantacji Szpiku
Lublin

Other trials in Poland

Czechia1 site

Fakultni nemocnice Kralovske Vinohrady
Prague

Other trials in Czechia

Norway1 site

Oslo University Hospital
Oslo, 0424

Other trials in Norway

Switzerland1 site

University Hospital Basel
Basel, 4031

Other trials in Switzerland

United Kingdom1 site

Guy's Hospital
London, SE1 9RT

Other trials in United Kingdom

About this study

Official title: 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. 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
Being tested: Bezuclastinib Tablets (Formulation A), Bezuclastinib Tablets (Formulation B), Placebo Tablets
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
Medical subject headings: Mastocytosis, Mastocytosis, Systemic, Immune Complex Diseases, Immune System Diseases, Hypersensitivity, Hematologic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Bezuclastinib Tablets (Formulation A)Drug
Also called CGT9486, PLX9486
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
Bezuclastinib Tablets (Formulation B)Drug
Also called CGT9486, PLX9486
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
Placebo TabletsDrug
Placebo will be administered orally, once daily continuously for 28-day cycles

Study groups in NCT05186753
Study group	Role	What they receive
(Part 1a) Bezuclastinib Dose 1 + BSC	Experimental	Not described Receives: Drug: Bezuclastinib Tablets (Formulation A)
(Part 1a) Bezuclastinib Dose 2 + BSC	Experimental	Not described Receives: Drug: Bezuclastinib Tablets (Formulation A)
(Part 1a) Placebo + BSC	Placebo comparator	Not described Receives: Drug: Placebo Tablets
(Part 1b) Bezuclastinib Dose 1 + BSC	Experimental	Not described Receives: Drug: Bezuclastinib Tablets (Formulation B)
(Part 1b) Bezuclastinib Dose 2 + BSC	Experimental	Not described Receives: Drug: Bezuclastinib Tablets (Formulation B)
(Part 1b) Placebo + BSC	Placebo comparator	Not described Receives: Drug: Placebo Tablets
(Part 2) Bezuclastinib Selected Dose + BSC	Experimental	Not described Receives: Drug: Bezuclastinib Tablets (Formulation B)
(Part 2) Placebo + BSC	Placebo comparator	Not described Receives: Drug: Placebo Tablets
(Part 3) Bezuclastinib + BSC	Experimental	Not described Receives: Drug: Bezuclastinib Tablets (Formulation A); Drug: Bezuclastinib Tablets (Formulation B)
(Prior Therapy Sub-study) Bezuclastinib	Experimental	Not described Receives: Drug: Bezuclastinib Tablets (Formulation B)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 3 months
Part 2: Efficacy of bezuclastinib at the selected dose versus placebo
Mean absolute change on the Mastocytosis Symptom Severity Daily Diary (MS2D2)
Measured: 24 Weeks
Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events
CTCAE v5
Measured: Up to 5 years

Secondary outcomes (14)

Part 2: Proportion of subjects who had at least 50% reduction in serum tryptase
Measured: 24 weeks
Part 2: Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction
Measured: 24 weeks
Part 2: Determine responder rates of subjects treated with bezuclastinib at the selected dose versus placebo
Proportion of subjects with at least a 30% reduction of the total symptom score (TSS) on the MS2D2.
Proportion of subjects with at least a 50% reduction of the total symptom score (TSS) on the MS2D2.
Measured: 24 weeks
Part 2: Proportion of subjects who had at least 50% reduction in mast cell burden
Measured: 24 weeks
Parts 1 & 2: Safety and tolerability of bezuclastinib as assessed by number of adverse events
CTCAE v5
Measured: Up to 24 weeks
Parts 1, 2, & 3: Change and percent change in patient reported outcome (PRO) measures
Measured: Up to 5 years
Parts 1 & 3: Change and percent change in serum tryptase
Measured: Up to 12 months
Parts 1 & 3: Change and percent change in bone marrow mast cells
Measured: Up to 18 months
Part 1: Assess the pharmacokinetics (PK) of bezuclastinib in subjects with NonAdvSM
Plasma concentrations of CGT9846
Measured: 3 months
Part 2: Determine mean change from baseline in predetermined PRO sub-domain and individual item scores
Measured: 24 weeks
Parts 2 & 3: Determine change of the lead (most severe) symptom and lead (most severe) subdomain of the MS2D2 in subjects treated with bezuclastinib versus placebo
Change and percent change from baseline in the symptom score of the subject's most severe symptom.
Change and percent change from baseline in the MS2D2 subdomain score of the subject's most severe subdomain.
Measured: Up to 5 years
Part 3: Change and percent change in the levels of KIT D816V mutation allele burden
Measured: Up to 12 months
Part 3: To determine the efficacy of bezuclastinib at the selected dose
Proportion of subjects with at least a 50% reduction in MS2D2 TSS from baseline at 1 year and 2 years from start of bezuclastinib
Change and percent change from baseline in the MS2D2 TSS, subdomain, and individual item scores
Measured: Up to 2 years
Part 3: Usage of concomitant medications as rescue therapy for NonAdvSM and changes from baseline in rescue therapy and best supportive care medications regimen
Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Jun 2022Jan 2030

First posted11 Jan 2022
Study start27 Jun 2022
Primary completion22 May 2025
Study completionJan 2030 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for SSMStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: 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.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 237 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05186753
Sponsor's protocol ID: CGT9486-21-202
Status last verified: Oct 2026
First submitted: 19 Nov 2021
Last updated: 22 Oct 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No