Clinical trial NCT05208047: (Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Lead sponsor: Cogent Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-26
Enrollment: 442
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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.


Eligibility criteria: 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.
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

Key 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)

Primary outcomes:
measure: Part 1a - pharmacokinetics - Cmax
timeFrame: 16 days
measure: Part 1a - pharmacokinetics - AUC
timeFrame: 16 days
measure: Part 1b - pharmacokinetics - Cmax
timeFrame: 14 days
measure: Part 1b - pharmacokinetics - AUC
timeFrame: 14 days
measure: Part 1b - pharmacokinetics - Tmax
timeFrame: 14 days
measure: Part 2 - Progression Free Survival (PFS)
timeFrame: Approximately 48 months
measure: DDI Substudy - pharmacokinetics - AUC
timeFrame: 16 days
measure: DDI Substudy - pharmacokinetics - Cmax
timeFrame: 14 days
Secondary outcomes:
measure: All Study Parts - observing the safety of each treatment regimen.
timeFrame: Approximately 48 months
measure: All Study Parts - observing the safety of each treatment regimen.
timeFrame: Approximately 48 months
measure: All Study Parts - observing the safety of each treatment regimen.
timeFrame: Approximately 48 months
measure: All Study Parts - observing the safety of each treatment regimen.
timeFrame: Approximately 48 months
measure: Part 1a, Part 1b, Part 2 - Overall Survival (OS)
timeFrame: Approximately 48 months
measure: Part 1a, Part 1b, Part 2 - Objective Response Rate (ORR)
timeFrame: Approximately 48 months
measure: Part 1a, Part 1b, Part 2 - Disease Control Rate (DCR)
timeFrame: Approximately 48 months
measure: Part 1a, Part 1b. Part 2 - Time to response (TTR)
timeFrame: Approximately 48 months
measure: Part 1a, Part 1b, Part 2 - Duration of Response (DOR)
timeFrame: Approximately 48 months
measure: Part 2 Only - European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30)
timeFrame: Approximately 48 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Tucson
country: United States
facility: University of Arizona- Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: San Diego
country: United States
facility: University of California, San Diego (UCSD)
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami - Sylvester Comprehensive Cancer Center
state: Florida
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Center
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Hillman Cancer Center
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin - Carbone Cancer Center
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming
city: Córdoba
country: Argentina
facility: Instituto Oncologico de Cordoba (IONC)
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Bankstown
country: Australia
facility: Bankstown-Lidcombe Hospital
city: Campinas
country: Brazil
facility: Hospital das Clinicas da Universidade Estadual de Campinas (UNICAMP)
city: Rio De Janeiro
country: Brazil
facility: lnstituto Nacional de Cancer - INCA
city: São Paulo
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
city: Edmonton
country: Canada
facility: Alberta Health Services Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
city: Montréal
country: Canada
facility: Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)
city: Santiago
country: Chile
facility: Instituto Oncologico FALP
city: Santiago
country: Chile
facility: Centro de Oncologia de Precision, Universidad Mayor
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
city: Hradec Králové
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc - Oncology clinic
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: AP-HM - Hôpital de la Timone
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Saint-Herblain
country: France
facility: ICO St-Herblain
city: Toulouse
country: France
facility: CHU de Toulouse - Hospital Rangueil
city: Villejuif
country: France
facility: Gustave Roussy
city: Bad Saarow
country: Germany
facility: Helios Klinikum Bad Saarow
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover- Urology Oncology
city: Mannheim
country: Germany
facility: Universitaetsmedizin Mannheim
city: Central
country: Hong Kong
facility: Humanity & Health Clinical Trial Centre
city: Jordon
country: Hong Kong
facility: Hong Kong United Oncology Centre
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital
city: Debrecen
country: Hungary
facility: Debreceni Egyetem, Klinikai Központ, Onkológiai Klinika
city: Aviano
country: Italy
facility: Centro Riferimento Oncologico - Aviano
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia
city: Candiolo
country: Italy
facility: IRCCS La Fondazione e l'Istituto di Candiolo
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
city: Roma
country: Italy
facility: Policlinico Universitario Campus Bio-Medico
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hosptial
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Aguascalientes
country: Mexico
facility: Centro de Investigacion Medica Aquascalientes (CIMA)
city: Monterrey
country: Mexico
facility: I Can Oncology Center SA De CV
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization S.C.
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL)
city: Groningen
country: Netherlands
facility: UMC Groningen
city: Nijmegen
country: Netherlands
facility: Stichting Radboud Universitair Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Bergen
country: Norway
facility: Haukeland University Hospital - Bergen
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Brzozów
country: Poland
facility: Szpital Specjalistyczny w Brzozowie
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach, Oddzial Chemioterapii Dziennej
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau Barcelona
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia - L'Hospitalet
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Santiago De Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago de Compostela
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Lund
country: Sweden
facility: Skane University Hospital Lund
city: Solna
country: Sweden
facility: Karolinska University Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital - Kaohsiung Branch
city: New Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital (VGHTP)
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou Branch (CGMHLK)
city: Cambridge
country: United Kingdom
facility: Cambridge Addenbrooke's Hospital
city: Glasgow
country: United Kingdom
facility: Beatson, West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Surrey
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
References: