(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors

NCT ID: NCT05208047

Last Updated: 2025-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

442 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-14

Study Completion Date

2026-09-30

Brief Summary

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This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination with sunitinib. This is a multi-part study that will enroll approximately 442 patients. Part 1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to be used in subsequent parts in approximately 20 patients who have received at least one prior line of therapy for GIST and 2) evaluating the potential for drug-drug interactions between CGT9486 and sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388 patients who are intolerant to, or who failed prior treatment with imatinib only and will compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being randomized in a 1:1 manner. Additionally, a drug-drug interactions substudy will investigate the potential for CGT9486 to be a CYP3A4 inducer in approximately 16 patients who have received at least one prior line of therapy for GIST.

Detailed Description

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Conditions

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Advanced Gastrointestinal Stromal Tumors Metastatic Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a multi-part study: Part 1a is a single-arm design, Part 1b is a two-arm parallel design drug-drug interaction evaluation in the first treatment cycle and single-arm design in subsequent treatment cycles, and Part 2 is a randomized two-arm parallel comparator study. The DDI substudy is a single-arm, fixed-sequence, crossover design to investigate the potential for CGT9486 to be a CYP3A4 inducer.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1a

CGT9486 plus sunitinib 37.5 mg QD

Group Type EXPERIMENTAL

CGT9486 plus sunitinib

Intervention Type DRUG

Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.

Part 2 - Experimental Group

CGT9486 plus sunitinib 37.5 mg QD

Group Type EXPERIMENTAL

CGT9486 plus sunitinib

Intervention Type DRUG

Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.

Part 2 - Control Group

sunitinib 37.5 mg QD

Group Type ACTIVE_COMPARATOR

Sunitinib

Intervention Type DRUG

Participants will receive sunitinib orally until study stopping rules are met.

Part 1b - DDI Cohort 1

CGT9486 plus sunitinib 37.5 mg QD

Group Type EXPERIMENTAL

CGT9486

Intervention Type DRUG

Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.

Part 1b - DDI Cohort 2

sunitinib 37.5 mg QD plus CGT9486

Group Type EXPERIMENTAL

Sunitinib

Intervention Type DRUG

Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.

DDI Substudy (Midazolam)

Midazolam, CGT9486, sunitinib

Group Type EXPERIMENTAL

Midazolam

Intervention Type DRUG

Participants will receive a single-dose of midazolam on Day 1 and Day 16

CGT9486 plus sunitinib

Intervention Type DRUG

Patients will receive CGT9486 orally starting on Day 2 and sunitinib starting on Day 16 until study stopping rules are met.

Interventions

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CGT9486 plus sunitinib

Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.

Intervention Type DRUG

CGT9486

Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.

Intervention Type DRUG

Sunitinib

Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.

Intervention Type DRUG

Sunitinib

Participants will receive sunitinib orally until study stopping rules are met.

Intervention Type DRUG

Midazolam

Participants will receive a single-dose of midazolam on Day 1 and Day 16

Intervention Type DRUG

CGT9486 plus sunitinib

Patients will receive CGT9486 orally starting on Day 2 and sunitinib starting on Day 16 until study stopping rules are met.

Intervention Type DRUG

Other Intervention Names

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sunitinib - Part 1b sunitinib - Part 2

Eligibility Criteria

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Inclusion Criteria

1. Histologically confirmed locally advanced, metastatic, and/or unresectable GIST. Molecular pathology report must be available for Part 2; if molecular pathology report is unavailable or inadequate, an archival or fresh tumor tissue sample will be required to evaluate mutational status prior to randomization.
2. Documented disease progression on or intolerance to imatinib
3. Subjects must have received the following treatment:

DDI Substudy/Part 1a: Treatment with ≥1 prior lines of therapy for GIST Part 1b: Treatment with ≥2 prior TKI for GISTs Part 2: Prior treatment with imatinib only
4. Have at least 1 measurable lesion according to mRECIST v1.1 (Part1a, Part 1b, Part 2)
5. ECOG - 0 to 2
6. Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits

Exclusion Criteria

1. Known PDGFR driving mutations or known succinate dehydrogenase deficiency
2. Clinically significant cardiac disease
3. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug
4. Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption
5. Any active bleeding excluding hemorrhoidal or gum bleeding
6. Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody.
7. Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
8. Received strong CYP3A4 inhibitors or inducers
9. Received sunitinib within 3 weeks (Part 1a, Part 1b, DDI Substudy)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cogent Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Mayo Clinic

Scottsdale, Arizona, United States

Site Status

University of Arizona- Cancer Center

Tucson, Arizona, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

University of California, Los Angeles (UCLA)

Los Angeles, California, United States

Site Status

University of California, San Diego (UCSD)

San Diego, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

University of Colorado Denver

Denver, Colorado, United States

Site Status

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Mid Florida Hematology and Oncology Center

Orange City, Florida, United States

Site Status

Orlando Health Cancer Institute

Orlando, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Site Status

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

University of Toledo Medical Center

Toledo, Ohio, United States

Site Status

Oregon Health & Science University (OHSU)

Portland, Oregon, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

University of Tennessee

Knoxville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status

University of Wisconsin - Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

Instituto Alexander Fleming

Buenos Aires, , Argentina

Site Status

Instituto Oncologico de Cordoba (IONC)

Córdoba, , Argentina

Site Status

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

Bankstown-Lidcombe Hospital

Bankstown, , Australia

Site Status

Hospital das Clinicas da Universidade Estadual de Campinas (UNICAMP)

Campinas, , Brazil

Site Status

lnstituto Nacional de Cancer - INCA

Rio de Janeiro, , Brazil

Site Status

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

São Paulo, , Brazil

Site Status

Alberta Health Services Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Tom Baker Cancer Center

Calgary, , Canada

Site Status

Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)

Montreal, , Canada

Site Status

Instituto Oncologico FALP

Santiago, , Chile

Site Status

Centro de Oncologia de Precision, Universidad Mayor

Santiago, , Chile

Site Status

Masarykuv onkologicky ustav

Brno, , Czechia

Site Status

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Site Status

Fakultni nemocnice Olomouc - Oncology clinic

Olomouc, , Czechia

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Aarhus University Hospital

Aarhus, , Denmark

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Institut Bergonie

Bordeaux, , France

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Centre Oscar Lambret

Lille, , France

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Centre Leon Berard

Lyon, , France

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AP-HM - Hôpital de la Timone

Marseille, , France

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Centre Eugene Marquis

Rennes, , France

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ICO St-Herblain

Saint-Herblain, , France

Site Status

CHU de Toulouse - Hospital Rangueil

Toulouse, , France

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Gustave Roussy

Villejuif, , France

Site Status

Helios Klinikum Bad Saarow

Bad Saarow, , Germany

Site Status

Helios Klinikum Berlin-Buch

Berlin, , Germany

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Universitaetsklinikum Essen

Essen, , Germany

Site Status

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

Medizinische Hochschule Hannover- Urology Oncology

Hanover, , Germany

Site Status

Universitaetsmedizin Mannheim

Mannheim, , Germany

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Humanity & Health Clinical Trial Centre

Central, , Hong Kong

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Hong Kong United Oncology Centre

Jordon, , Hong Kong

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Prince of Wales Hospital

Shatin, , Hong Kong

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Debreceni Egyetem, Klinikai Központ, Onkológiai Klinika

Debrecen, , Hungary

Site Status

Centro Riferimento Oncologico - Aviano

Aviano, , Italy

Site Status

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

Bologna, , Italy

Site Status

ASST degli Spedali Civili di Brescia

Brescia, , Italy

Site Status

IRCCS La Fondazione e l'Istituto di Candiolo

Candiolo, , Italy

Site Status

Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

Site Status

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"

Meldola, , Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

Istituto Europeo di Oncologia

Milan, , Italy

Site Status

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, , Italy

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Policlinico Universitario Campus Bio-Medico

Roma, , Italy

Site Status

Istituto Clinico Humanitas

Rozzano, , Italy

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Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento

Verona, , Italy

Site Status

Centro de Investigacion Medica Aquascalientes (CIMA)

Aguascalientes, , Mexico

Site Status

I Can Oncology Center SA De CV

Monterrey, , Mexico

Site Status

Oaxaca Site Management Organization S.C.

Oaxaca City, , Mexico

Site Status

Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL)

Amsterdam, , Netherlands

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UMC Groningen

Groningen, , Netherlands

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Stichting Radboud Universitair Medisch Centrum

Nijmegen, , Netherlands

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Erasmus MC

Rotterdam, , Netherlands

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Haukeland University Hospital - Bergen

Bergen, , Norway

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Oslo University Hospital

Oslo, , Norway

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Szpital Specjalistyczny w Brzozowie

Brzozów, , Poland

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Centrum Onkologii im. Prof. Franciszka Lukaszczyka

Bydgoszcz, , Poland

Site Status

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach, Oddzial Chemioterapii Dziennej

Gliwice, , Poland

Site Status

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow

Warsaw, , Poland

Site Status

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

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Seoul National University Hosptial

Seoul, , South Korea

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Asan Medical Center

Seoul, , South Korea

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Samsung Medical Center

Seoul, , South Korea

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Korea University Guro Hospital

Seoul, , South Korea

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Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital de la Santa Creu i Sant Pau Barcelona

Barcelona, , Spain

Site Status

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, , Spain

Site Status

Hospital Clinico Universitario Virgen de la Arrixaca

El Palmar, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

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Hospital Clinico San Carlos

Madrid, , Spain

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Hospital Fundación Jiménez Díaz

Madrid, , Spain

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Hospital Universitario 12 de Octubre

Madrid, , Spain

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Hospital Clinico Universitario de Santiago de Compostela

Santiago de Compostela, , Spain

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Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Skane University Hospital Lund

Lund, , Sweden

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Karolinska University Hospital

Solna, , Sweden

Site Status

Chang Gung Memorial Hospital - Kaohsiung Branch

Kaohsiung City, , Taiwan

Site Status

National Taiwan University Hospital

New Taipei City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

Taipei Veterans General Hospital (VGHTP)

Taipei, , Taiwan

Site Status

Chang Gung Memorial Hospital - Linkou Branch (CGMHLK)

Taoyuan District, , Taiwan

Site Status

Cambridge Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Beatson, West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

University College London Hospital

London, , United Kingdom

Site Status

Guy's Hospital

London, , United Kingdom

Site Status

Royal Marsden Hospital - Surrey

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, , United Kingdom

Site Status

Countries

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United States Argentina Australia Brazil Canada Chile Czechia Denmark France Germany Hong Kong Hungary Italy Mexico Netherlands Norway Poland South Korea Spain Sweden Taiwan United Kingdom

Other Identifiers

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CGT9486-21-301

Identifier Type: -

Identifier Source: org_study_id

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