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

A Phase 3 Randomized, Open-Label, Multicenter Clinical Study of CGT9486+Sunitinib vs. Sunitinib in Subjects With Locally Advanced, Unresectable, or Metastatic Gastrointestinal Stromal Tumors

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 482 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 Gastrointestinal Stromal Tumors (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. This study also contains two substudies: 1) a drug-drug interactions (DDI) substudy will investigate the potential for CGT9486 to be a Cytochrome P450 (CYP)3A4 inducer in approximately 16 patients who have received at least one prior line of therapy for GIST and 2) a substudy intended to test the efficacy of bezuclastinib and sunitinib as first-line (1L) treatment of GIST in approximately 40 participants with KIT exon 9 mutations and no prior systemic therapy (with the exception of up to 10 subjects with ongoing imatinib therapy of ≤4 weeks).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Cancer; Advanced Gastrointestinal Stromal Tumors
• Intervention / Treatment: Drug: Sunitinib; Drug: Sunitinib; Drug: CGT9486; Drug: Midazolam; Drug: CGT9486; Drug: CGT9486; Drug: Sunitinib; Drug: CGT9486; Drug: Sunitinib

• Study Type: Interventional
• Enrollment (Estimated): 482
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Cogent Biosciences; Phone Number: 617-945-5576; Email: peakinfo@cogentbio.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ANZ
    • Active, not recruiting
    • Instituto Alexander Fleming
  • Córdoba, Argentina, X5000HWE
    • Active, not recruiting
    • Instituto Oncologico de Cordoba (IONC)
• Australia
  • Bankstown, Australia, 2200
    • Active, not recruiting
    • Bankstown-Lidcombe Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Active, not recruiting
      • Sir Charles Gairdner Hospital
• Brazil
  • Campinas, Brazil, 130.83-888
    • Active, not recruiting
    • Hospital das Clinicas da Universidade Estadual de Campinas (UNICAMP)
  • Rio de Janeiro, Brazil, 20.230-130
    • Active, not recruiting
    • lnstituto Nacional de Cancer - INCA
  • São Paulo, Brazil, 09060-650
    • Active, not recruiting
    • CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
• Canada
  • Calgary, Canada, T2N 4N2
    • Active, not recruiting
    • Tom Baker Cancer Center
  • Montreal, Canada, HIT 2M4
    • Active, not recruiting
    • Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Active, not recruiting
      • Alberta Health Services Cross Cancer Institute
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Active, not recruiting
      • Princess Margaret Hospital
• Chile
  • Santiago, Chile, 7500921
    • Active, not recruiting
    • Instituto Oncológico FALP
  • Santiago, Chile, 7560908
    • Active, not recruiting
    • Centro de Oncologia de Precision, Universidad Mayor
• Czechia
  • Brno, Czechia, 65653
    • Active, not recruiting
    • Masarykuv onkologicky ustav
  • Hradec Králové, Czechia, 500 05
    • Withdrawn
    • Fakultni nemocnice Hradec Kralove
  • Olomouc, Czechia, 77900
    • Active, not recruiting
    • Fakultni nemocnice Olomouc - Oncology clinic
• Denmark
  • Aarhus, Denmark, 8200
    • Active, not recruiting
    • Aarhus University Hospital
• France
  • Bordeaux, France, 33076
    • Active, not recruiting
    • Institut Bergonie
  • Lille, France, 59000
    • Active, not recruiting
    • Centre Oscar Lambret
  • Lyon, France, 69008
    • Active, not recruiting
    • Centre Leon Berard
  • Marseille, France, 13005
    • Active, not recruiting
    • AP-HM - Hôpital de la Timone
  • Rennes, France, 35042
    • Active, not recruiting
    • Centre Eugene Marquis
  • Saint-Herblain, France, 44800
    • Active, not recruiting
    • ICO St-Herblain
  • Toulouse, France, 31400
    • Active, not recruiting
    • CHU de Toulouse - Hospital Rangueil
  • Villejuif, France, 94805
    • Active, not recruiting
    • Gustave Roussy
• Germany
  • Bad Saarow, Germany, 15526
    • Active, not recruiting
    • Helios Klinikum Bad Saarow
  • Berlin, Germany, 13125
    • Active, not recruiting
    • Helios Klinikum Berlin-Buch
  • Essen, Germany, 45147
    • Active, not recruiting
    • Universitaetsklinikum Essen
  • Hamburg, Germany, 20246
    • Active, not recruiting
    • Universitaetsklinikum Hamburg-Eppendorf
  • Hanover, Germany, 30625
    • Active, not recruiting
    • Medizinische Hochschule Hannover- Urology Oncology
  • Mannheim, Germany, 68167
    • Active, not recruiting
    • Universitaetsmedizin Mannheim
• Hong Kong
  • Central, Hong Kong
    • Withdrawn
    • Humanity & Health Clinical Trial Centre
  • Jordon, Hong Kong
    • Active, not recruiting
    • Hong Kong United Oncology Centre
  • Shatin, Hong Kong
    • Active, not recruiting
    • Prince of Wales Hospital
• Hungary
  • Debrecen, Hungary, 4032
    • Active, not recruiting
    • Debreceni Egyetem, Klinikai Központ, Onkológiai Klinika
• Italy
  • Aviano, Italy, 33081
    • Active, not recruiting
    • Centro Riferimento Oncologico - Aviano
  • Bologna, Italy, 40138
    • Active, not recruiting
    • Irccs Azienda Ospedaliero-Universitaria Di Bologna - Policlinico Di Sant'Orsola
  • Brescia, Italy, 25123
    • Active, not recruiting
    • ASST degli Spedali Civili di Brescia
  • Candiolo, Italy, 10060
    • Withdrawn
    • IRCCS La Fondazione e l'Istituto di Candiolo
  • Florence, Italy, 50134
    • Active, not recruiting
    • Azienda Ospedaliero-Universitaria Careggi
  • Meldola, Italy, 47014
    • Active, not recruiting
    • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"
  • Milan, Italy, 20133
    • Active, not recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy, 20141
    • Active, not recruiting
    • Istituto Europeo Di Oncologia
  • Palermo, Italy, 90127
    • Active, not recruiting
    • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
  • Roma, Italy, 00128
    • Active, not recruiting
    • Policlinico Universitario Campus Bio-Medico
  • Rozzano, Italy, 20089
    • Active, not recruiting
    • Istituto Clinico Humanitas
  • Verona, Italy, 31726
    • Active, not recruiting
    • Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento
• Mexico
  • Aguascalientes, Mexico, 20116
    • Withdrawn
    • Centro de Investigacion Medica Aquascalientes (CIMA)
  • Monterrey, Mexico, 64710
    • Active, not recruiting
    • I Can Oncology Center SA De CV
  • Oaxaca City, Mexico, 68000
    • Withdrawn
    • Oaxaca Site Management Organization S.C.
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Active, not recruiting
    • Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL)
  • Groningen, Netherlands, 9713 GZ
    • Active, not recruiting
    • UMC Groningen
  • Nijmegen, Netherlands, 6525 GA
    • Active, not recruiting
    • Stichting Radboud Universitair Medisch Centrum
  • Rotterdam, Netherlands, 3015 GD
    • Active, not recruiting
    • Erasmus MC
• Norway
  • Bergen, Norway, 5021
    • Active, not recruiting
    • Haukeland University Hospital - Bergen
  • Oslo, Norway, 0310
    • Active, not recruiting
    • Oslo University Hospital
• Poland
  • Brzozów, Poland, 36-200
    • Active, not recruiting
    • Szpital Specjalistyczny w Brzozowie
  • Bydgoszcz, Poland, 85-796
    • Withdrawn
    • Centrum Onkologii im. Prof. Franciszka Lukaszczyka
  • Gliwice, Poland, 44-102
    • Active, not recruiting
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach, Oddzial Chemioterapii Dziennej
  • Warsaw, Poland, 02-781
    • Active, not recruiting
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow
• South Korea
  • Seoul, South Korea, 06351
    • Active, not recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 08308
    • Active, not recruiting
    • Korea University Guro Hospital
  • Seoul, South Korea, 05505
    • Active, not recruiting
    • Asan Medical Center
  • Seoul, South Korea, 03080
    • Active, not recruiting
    • Seoul National University Hosptial
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea, 10408
      • Withdrawn
      • National Cancer Center
• Spain
  • Barcelona, Spain, 08035
    • Active, not recruiting
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08908
    • Active, not recruiting
    • Institut Catala d'Oncologia - L'Hospitalet
  • Barcelona, Spain, 08041
    • Withdrawn
    • Hospital de la Santa Creu i Sant Pau Barcelona
  • El Palmar, Spain, 30120
    • Withdrawn
    • Hospital Clínico Universitario Virgen de la Arrixaca
  • Madrid, Spain, 28041
    • Active, not recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Active, not recruiting
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28007
    • Active, not recruiting
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28040
    • Active, not recruiting
    • Hospital Fundación Jiménez Díaz
  • Santiago de Compostela, Spain, 15706
    • Active, not recruiting
    • Hospital Clínico Universitario de Santiago de Compostela
  • Seville, Spain, 41013
    • Active, not recruiting
    • Hospital Universitario Virgen del Rocio
  • Zaragoza, Spain, 50009
    • Withdrawn
    • Hospital Universitario Miguel Servet
• Sweden
  • Lund, Sweden, 22185
    • Active, not recruiting
    • Skane University Hospital Lund
  • Solna, Sweden, 171 76
    • Active, not recruiting
    • Karolinska University Hospital
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Active, not recruiting
    • Chang Gung Memorial Hospital - Kaohsiung Branch
  • New Taipei City, Taiwan, 10002
    • Active, not recruiting
    • National Taiwan University Hospital
  • Taichung, Taiwan, 40447
    • Active, not recruiting
    • China Medical University Hospital
  • Taipei, Taiwan, 11217
    • Active, not recruiting
    • Taipei Veterans General Hospital (VGHTP)
  • Taoyuan, Taiwan, 33305
    • Active, not recruiting
    • Chang Gung Memorial Hospital - Linkou Branch (CGMHLK)
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Active, not recruiting
    • Cambridge Addenbrooke's Hospital
  • Glasgow, United Kingdom, G12 0YN
    • Withdrawn
    • Beatson, West of Scotland Cancer Centre
  • London, United Kingdom, NW1 2PG
    • Active, not recruiting
    • University College London Hospital
  • London, United Kingdom, SW3 6JJ
    • Active, not recruiting
    • Royal Marsden Hospital - Surrey
  • London, United Kingdom, SE1 9RT
    • Withdrawn
    • Guy's Hospital
  • Manchester, United Kingdom, M20 4BX
    • Active, not recruiting
    • The Christie NHS Foundation Trust
  • Sheffield, United Kingdom, S10 2SJ
    • Active, not recruiting
    • Sheffield Teaching Hospitals NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Withdrawn
      • University of Alabama at Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Active, not recruiting
      • Mayo Clinic
    • Tucson, Arizona, United States, 85719
      • Active, not recruiting
      • University of Arizona- Cancer Center
  • California
    • Duarte, California, United States, 91010
      • Active, not recruiting
      • City of Hope
    • Los Angeles, California, United States, 90404
      • Active, not recruiting
      • University of California, Los Angeles (UCLA)
    • San Diego, California, United States, 92093
      • Active, not recruiting
      • University of California, San Diego (UCSD)
    • San Francisco, California, United States, 94158
      • Active, not recruiting
      • University of California, San Francisco
  • Colorado
    • Denver, Colorado, United States, 80204
      • Active, not recruiting
      • University of Colorado Denver
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • MedStar Washington Hospital Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Active, not recruiting
      • Mayo Clinic Jacksonville
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami - Sylvester Comprehensive Cancer Center
    • Orange City, Florida, United States, 32763
      • Withdrawn
      • Mid Florida Hematology and Oncology Center
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Orlando Health Cancer Institute
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Active, not recruiting
      • University of Iowa Hospital and Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Active, not recruiting
      • University of Kansas Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Active, not recruiting
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Active, not recruiting
      • University of Michigan Comprehensive Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Active, not recruiting
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63130
      • Recruiting
      • Washington University
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Recruiting
      • Nebraska Methodist Hospital
  • New York
    • Buffalo, New York, United States, 14203
      • Active, not recruiting
      • Roswell Park Comprehensive Cancer Center
    • New York, New York, United States, 10021
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Active, not recruiting
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Active, not recruiting
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Active, not recruiting
      • The Ohio State University Comprehensive Cancer Center
    • Toledo, Ohio, United States, 43614
      • Withdrawn
      • University of Toledo Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Active, not recruiting
      • Oregon Health & Science University (OHSU)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Active, not recruiting
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • Active, not recruiting
      • University of Pittsburgh Medical Center - Hillman Cancer Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Withdrawn
      • University of Tennessee
    • Nashville, Tennessee, United States, 37232
      • Active, not recruiting
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030-4009
      • Active, not recruiting
      • The University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Active, not recruiting
      • Fred Hutchinson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Active, not recruiting
      • University of Wisconsin - Carbone 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. 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. (GIST 1L Substudy: must have documented mutation in KIT Exon 9 with an available molecular pathology report; archival or fresh tumor tissue sample will be required)
2. Documented disease progression on or intolerance to imatinib (Part 1a, Part 1b, Part 2, DDI Substudy)

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
   • GIST 1L Substudy: No prior systemic therapy for GIST including adjuvant therapy. Exception: up to 10 subjects with ongoing imatinib therapy of ≤4 weeks
4. Have at least 1 measurable lesion according to mRECIST v1.1 (Part1a, Part 1b, Part 2, GIST 1L Substudy)

5. Eastern Cooperative Oncology Group (ECOG) Status

   • 0 to 2 (Part 1a, Part 1b, Part 2, DDI Substudy)
   • 0 to 1 (GIST 1L Substudy)
6. Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits

Key Exclusion Criteria:

1. Known Platelet-Derived Growth Factor Receptor (PDGFR) driving mutations or known succinate dehydrogenase deficiency (Part 1a, Part 1b, Part 2, DDI Substudy)
2. Clinically significant cardiac disease
3. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug (Part 1a, Part 1b, Part 2, DDI Substudy)
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 (Part 1a, Part 1b, Part 2, DDI Substudy)
9. Received sunitinib within 3 weeks (Part 1a, Part 1b, DDI Substudy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1a; CGT9486 plus sunitinib 37.5 mg QD	Drug: Sunitinib; Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Other Names: sunitinib - Part 1b; Drug: Sunitinib; Participants will receive sunitinib orally until study stopping rules are met.; Other Names: sunitinib - Part 2; Drug: CGT9486; Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: CGT9486; Participants will receive CGT9486 orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: CGT9486; Participants will receive CGT9486 orally starting on Day 2 until study stopping rules are met.; Drug: Sunitinib; Participants will receive CGT9486 until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Drug: CGT9486; Participants will receive sunitinib until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: Sunitinib; Participants will receive sunitinib orally starting on Day 16 until study stopping rules are met.
Experimental: Part 2 - Experimental Group; CGT9486 plus sunitinib 37.5 mg QD	Drug: Sunitinib; Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Other Names: sunitinib - Part 1b; Drug: Sunitinib; Participants will receive sunitinib orally until study stopping rules are met.; Other Names: sunitinib - Part 2; Drug: CGT9486; Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: CGT9486; Participants will receive CGT9486 orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: CGT9486; Participants will receive CGT9486 orally starting on Day 2 until study stopping rules are met.; Drug: Sunitinib; Participants will receive CGT9486 until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Drug: CGT9486; Participants will receive sunitinib until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: Sunitinib; Participants will receive sunitinib orally starting on Day 16 until study stopping rules are met.
Active Comparator: Part 2 - Control Group; sunitinib 37.5 mg QD	Drug: Sunitinib; Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Other Names: sunitinib - Part 1b; Drug: Sunitinib; Participants will receive sunitinib orally until study stopping rules are met.; Other Names: sunitinib - Part 2; Drug: Sunitinib; Participants will receive CGT9486 until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Drug: Sunitinib; Participants will receive sunitinib orally starting on Day 16 until study stopping rules are met.
Experimental: Part 1b - DDI Cohort 1; CGT9486 plus sunitinib 37.5 mg QD	Drug: Sunitinib; Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Other Names: sunitinib - Part 1b; Drug: Sunitinib; Participants will receive sunitinib orally until study stopping rules are met.; Other Names: sunitinib - Part 2; Drug: CGT9486; Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: CGT9486; Participants will receive CGT9486 orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: CGT9486; Participants will receive CGT9486 orally starting on Day 2 until study stopping rules are met.; Drug: Sunitinib; Participants will receive CGT9486 until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Drug: CGT9486; Participants will receive sunitinib until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: Sunitinib; Participants will receive sunitinib orally starting on Day 16 until study stopping rules are met.
Experimental: Part 1b - DDI Cohort 2; sunitinib 37.5 mg QD plus CGT9486	Drug: Sunitinib; Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Other Names: sunitinib - Part 1b; Drug: Sunitinib; Participants will receive sunitinib orally until study stopping rules are met.; Other Names: sunitinib - Part 2; Drug: CGT9486; Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: CGT9486; Participants will receive CGT9486 orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: CGT9486; Participants will receive CGT9486 orally starting on Day 2 until study stopping rules are met.; Drug: Sunitinib; Participants will receive CGT9486 until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Drug: CGT9486; Participants will receive sunitinib until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: Sunitinib; Participants will receive sunitinib orally starting on Day 16 until study stopping rules are met.
Experimental: DDI Substudy (Midazolam); Midazolam, CGT9486, sunitinib	Drug: Sunitinib; Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Other Names: sunitinib - Part 1b; Drug: Sunitinib; Participants will receive sunitinib orally until study stopping rules are met.; Other Names: sunitinib - Part 2; Drug: CGT9486; Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: Midazolam; Participants will receive a single-dose of midazolam on Day 1 and Day 16; Drug: CGT9486; Participants will receive CGT9486 orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: CGT9486; Participants will receive CGT9486 orally starting on Day 2 until study stopping rules are met.; Drug: Sunitinib; Participants will receive CGT9486 until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Drug: CGT9486; Participants will receive sunitinib until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: Sunitinib; Participants will receive sunitinib orally starting on Day 16 until study stopping rules are met.
Experimental: GIST 1L Substudy; CGT9486, sunitinib	Drug: Sunitinib; Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Other Names: sunitinib - Part 1b; Drug: Sunitinib; Participants will receive sunitinib orally until study stopping rules are met.; Other Names: sunitinib - Part 2; Drug: CGT9486; Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: CGT9486; Participants will receive CGT9486 orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: CGT9486; Participants will receive CGT9486 orally starting on Day 2 until study stopping rules are met.; Drug: Sunitinib; Participants will receive CGT9486 until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.; Drug: CGT9486; Participants will receive sunitinib until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.; Other Names: Bezuclastinib; Drug: Sunitinib; Participants will receive sunitinib orally starting on Day 16 until study stopping rules are met.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
All Study Parts - observing the safety of each treatment regimen.	Incidence and severity of Adverse Events from first dose of study drug	Approximately 48 months
All Study Parts - observing the safety of each treatment regimen.	Incidence and severity of Serious Adverse Events from first dose of study drug	Approximately 48 months
All Study Parts - observing the safety of each treatment regimen.	Incidence of Adverse Events leading to dose modifications from first dose of study drug	Approximately 48 months
All Study Parts - observing the safety of each treatment regimen.	Change from baseline in laboratory results	Approximately 48 months
Part 2 Only - European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30)	Change in individual scores in patients with locally advanced, unresectable, or metastatic GIST treated with CGT9486 in combination with sunitinib compared with patients treated with sunitinib monotherapy. The scale comprises 30 questions, 24 of which are aggregated into 9 multi-item scales, to include 5 functioning scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting) and 1 global health status scale. The remaining 6 single-item scales assess symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact). All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.	Approximately 48 months
Part 1a, Part 1b, Part 2 - Overall Survival (OS)	Time from first dose to death due to any cause	Approximately 48 months
Part 1a, Part 1b, Part 2 - Objective Response Rate (ORR)	Percentage of subjects who achieved documented complete response (CR) + confirmed partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	Approximately 48 months
Part 1a, Part 1b, Part 2 - Disease Control Rate (DCR)	Percentage of subjects who achieved CR + PR + stable disease (SD) at 16 weeks	Approximately 48 months
Part 1a, Part 1b. Part 2 - Time to response (TTR)	Time from first dose to first documented response based on modified Response Evaluation Criteria in Solid Tumors Version 1.1	Approximately 48 months
Part 1a, Part 1b, Part 2 - Duration of Response (DOR)	Time from first response (CR or PR) to the date of progression or death from any cause, whichever occurs first	Approximately 48 months

Collaborators and Investigators

• Sponsor: Cogent Biosciences, Inc.
• Investigators: Study Director: Jessica Sachs, MD, Cogent Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Actual): September 30, 2025
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: December 23, 2021
• First Submitted That Met QC Criteria: January 14, 2022
• First Posted (Actual): January 26, 2022

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Metastatic; Unresectable; Midazolam; Solid Tumors; Gastrointestinal; GIST; KIT; Sunitinib; Drug-drug interaction; Gastrointestinal Stromal Tumors; Growth Inhibitors; Kinase Inhibitors; CGT9486; Bezuclastinib; PLX9486
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplastic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Gastrointestinal Stromal Tumors; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Indoles; Benzazepines; Pyrroles; Benzodiazepines; Sunitinib; Midazolam
• Other Study ID Numbers: CGT9486-21-301

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
• product manufactured in and exported from the U.S.: No