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

NCT05208047 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CGT9486-21-301
• Study Type: interventional
• Target: 442
• Locations: 22 countries
• Sites: 110

Brief Summary

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.

Conditions

Advanced Gastrointestinal Stromal Tumors; Metastatic Cancer

Keywords

Sunitinib; Solid Tumors; Gastrointestinal Stromal Tumors; Gastrointestinal; KIT; Kinase Inhibitors; Growth Inhibitors; CGT9486; Unresectable; Metastatic; GIST; Bezuclastinib; PLX9486; Midazolam; Drug-drug interaction

Outcome Measures

Primary Outcomes (8)

• Part 1a - pharmacokinetics - Cmax

  Maximum plasma concentration (Cmax)

  16 days

• Part 1a - pharmacokinetics - AUC

  Area under the plasma concentration-time curve (AUC)

  16 days

• Part 1b - pharmacokinetics - Cmax

  Maximum plasma concentration (Cmax)

  14 days

• Part 1b - pharmacokinetics - AUC

  Area under the plasma concentration-time curve (AUC)

  14 days

• Part 1b - pharmacokinetics - Tmax

  Time to maximum observed plasma concentration (Tmax)

  14 days

• Part 2 - Progression Free Survival (PFS)

  Time from first dose to documented disease progression or death due to any cause, whichever occurs first

  Approximately 48 months

• DDI Substudy - pharmacokinetics - AUC

  Area under the plasma concentration-time curve (AUC)

  16 days

• DDI Substudy - pharmacokinetics - Cmax

  Maximum plasma concentration (Cmax)

  14 days

Secondary Outcomes (10)

• All Study Parts - observing the safety of each treatment regimen.

  Approximately 48 months

• All Study Parts - observing the safety of each treatment regimen.

  Approximately 48 months

• All Study Parts - observing the safety of each treatment regimen.

  Approximately 48 months

• All Study Parts - observing the safety of each treatment regimen.

  Approximately 48 months

• Part 1a, Part 1b, Part 2 - Overall Survival (OS)

  Approximately 48 months

Study Arms (6)

Part 1a

EXPERIMENTAL

CGT9486 plus sunitinib 37.5 mg QD

Drug: CGT9486 plus sunitinib

Part 2 - Experimental Group

EXPERIMENTAL

CGT9486 plus sunitinib 37.5 mg QD

Drug: CGT9486 plus sunitinib

Part 2 - Control Group

ACTIVE COMPARATOR

sunitinib 37.5 mg QD

Drug: Sunitinib

Part 1b - DDI Cohort 1

EXPERIMENTAL

CGT9486 plus sunitinib 37.5 mg QD

Drug: CGT9486

Part 1b - DDI Cohort 2

EXPERIMENTAL

sunitinib 37.5 mg QD plus CGT9486

Drug: Sunitinib

DDI Substudy (Midazolam)

EXPERIMENTAL

Midazolam, CGT9486, sunitinib

Drug: Midazolam; Drug: CGT9486 plus sunitinib

Interventions

CGT9486 DRUG

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

Part 1b - DDI Cohort 1

Sunitinib DRUG

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

Also known as: sunitinib - Part 1b

Part 1b - DDI Cohort 2

Midazolam DRUG

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

DDI Substudy (Midazolam)

CGT9486 plus sunitinib DRUG

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

Part 1a; Part 2 - Experimental Group

Eligibility Criteria

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

You may qualify if:

• 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.
• Documented disease progression on or intolerance to imatinib
• 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
• Have at least 1 measurable lesion according to mRECIST v1.1 (Part1a, Part 1b, Part 2)
• ECOG - 0 to 2
• Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits

You may not qualify if:

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

Sponsors & Collaborators

• Cogent Biosciences, Inc.: lead

Study Sites (110)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

University of Arizona- Cancer Center

Tucson, Arizona, 85719, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California, Los Angeles (UCLA)

Los Angeles, California, 90404, United States

Location

University of California, San Diego (UCSD)

San Diego, California, 92093, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

University of Colorado Denver

Denver, Colorado, 80204, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

University of Wisconsin - Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

Instituto Alexander Fleming

Buenos Aires, C1426ANZ, Argentina

Location

Instituto Oncologico de Cordoba (IONC)

Córdoba, X5000HWE, Argentina

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Bankstown-Lidcombe Hospital

Bankstown, 2200, Australia

Location

Hospital das Clinicas da Universidade Estadual de Campinas (UNICAMP)

Campinas, 130.83-888, Brazil

Location

lnstituto Nacional de Cancer - INCA

Rio de Janeiro, 20.230-130, Brazil

Location

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

São Paulo, 09060-650, Brazil

Location

Alberta Health Services Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Tom Baker Cancer Center

Calgary, T2N 4N2, Canada

Location

Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)

Montreal, HIT 2M4, Canada

Location

Instituto Oncologico FALP

Santiago, 7500921, Chile

Location

Centro de Oncologia de Precision, Universidad Mayor

Santiago, 7560908, Chile

Location

Masarykuv onkologicky ustav

Brno, 65653, Czechia

Location

Fakultni nemocnice Olomouc - Oncology clinic

Olomouc, 77900, Czechia

Location

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

AP-HM - Hôpital de la Timone

Marseille, 13005, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

ICO St-Herblain

Saint-Herblain, 44800, France

Location

CHU de Toulouse - Hospital Rangueil

Toulouse, 31400, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover- Urology Oncology

Hanover, 30625, Germany

Location

Universitaetsmedizin Mannheim

Mannheim, 68167, Germany

Location

Hong Kong United Oncology Centre

Jordon, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Debreceni Egyetem, Klinikai Központ, Onkológiai Klinika

Debrecen, 4032, Hungary

Location

Centro Riferimento Oncologico - Aviano

Aviano, 33081, Italy

Location

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

Bologna, 40138, Italy

Location

ASST degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

Location

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"

Meldola, 47014, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, 90127, Italy

Location

Policlinico Universitario Campus Bio-Medico

Roma, 00128, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento

Verona, 31726, Italy

Location

I Can Oncology Center SA De CV

Monterrey, 64710, Mexico

Location

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

Amsterdam, 1066 CX, Netherlands

Location

UMC Groningen

Groningen, 9713 GZ, Netherlands

Location

Stichting Radboud Universitair Medisch Centrum

Nijmegen, 6525 GA, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Haukeland University Hospital - Bergen

Bergen, 5021, Norway

Location

Oslo University Hospital

Oslo, 0310, Norway

Location

Szpital Specjalistyczny w Brzozowie

Brzozów, 36-200, Poland

Location

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

Gliwice, 44-102, Poland

Location

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

Warsaw, 02-781, Poland

Location

Seoul National University Hosptial

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Clinico Universitario de Santiago de Compostela

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Skane University Hospital Lund

Lund, 22185, Sweden

Location

Karolinska University Hospital

Solna, 171 76, Sweden

Location

Chang Gung Memorial Hospital - Kaohsiung Branch

Kaohsiung City, 83301, Taiwan

Location

National Taiwan University Hospital

New Taipei City, 10002, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taipei Veterans General Hospital (VGHTP)

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital - Linkou Branch (CGMHLK)

Taoyuan District, 33305, Taiwan

Location

Cambridge Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

University College London Hospital

London, NW1 2PG, United Kingdom

Location

Royal Marsden Hospital - Surrey

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S10 2SJ, United Kingdom

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Gastrointestinal Stromal Tumors

Interventions

Sunitinib; Midazolam

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzodiazepines; Benzazepines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 23, 2021
• First Posted: January 26, 2022
• Study Start: April 14, 2022
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

PL (3); GB (5); TW (5); US (32); CA (4); AU (2); ES (8); KR (4); IT (11); DK (1); FR (8); HK (2); SE (2); NL (4); ME (1); DE (6); AR (2); HU (1); CL (2); CZ (2); NO (2); BR (3)