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

Metastatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05208047
• Other study ID #: CGT9486-21-301
• Status: Recruiting
• Phase: Phase 3
• Start date: April 14, 2022
• Est. completion date: September 2026

Study information

• Verified date: May 2024
• Source: Cogent Biosciences, Inc.
• Contact: Cogent Biosciences
• Phone: 617-945-5576
• Email: peakinfo[@]cogentbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 426 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 426
• Est. completion date: September 2026
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

• 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

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)

Related Conditions & MeSH terms

• Advanced Gastrointestinal Stromal Tumors
• Gastrointestinal Stromal Tumors
• Metastatic Cancer

Intervention

Drug:
• CGT9486 plus sunitinib
Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.
• CGT9486
Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.
• Sunitinib
Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.
• Sunitinib
Participants will receive sunitinib orally until study stopping rules are met.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Cogent Biosciences, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1a - pharmacokinetics - Cmax	Maximum plasma concentration (Cmax)	16 days
Primary	Part 1a - pharmacokinetics - AUC	Area under the plasma concentration-time curve (AUC)	16 days
Primary	Part 1b - pharmacokinetics - Cmax	Maximum plasma concentration (Cmax)	14 days
Primary	Part 1b - pharmacokinetics - AUC	Area under the plasma concentration-time curve (AUC)	14 days
Primary	Part 1b - pharmacokinetics - Tmax	Time to maximum observed plasma concentration (Tmax)	14 days
Primary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	All Study Parts - observing the safety of each treatment regimen.	Change from baseline in laboratory results	Approximately 48 months
Secondary	All Study Parts - Overall Survival (OS)	Time from first dose to death due to any cause	Approximately 48 months
Secondary	All Study Parts - 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
Secondary	All Study Parts - Disease Control Rate (DCR)	Percentage of subjects who achieved CR + PR + stable disease (SD) at 16 weeks	Approximately 48 months
Secondary	All Study Parts - 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
Secondary	All Study Parts - 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
Secondary	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