A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib

NCT03673501 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 1 other identifier: DCC-2618-03-002
• Study Type: interventional
• Target: 453
• Locations: 22 countries
• Sites: 121

Brief Summary

This is a 2-arm, randomized, open-label, international, multicenter study comparing the efficacy of ripretinib to sunitinib in GIST patients who progressed on or were intolerant to first-line anticancer treatment with imatinib. Approximately 426 patients will be randomized in a 1:1 ratio to ripretinib 150 mg once daily (continuous dosing for 6 week cycles) or sunitinib 50 mg once daily (6 week cycles, 4 weeks on, 2 weeks off).

Conditions

Gastrointestinal Stromal Tumors

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS) in the KIT Exon 11 Intent to Treat (ITT) Population

  PFS is defined as the interval between the date of randomization and the earliest documented evidence of disease progression based on the independent radiologic review using modified RECIST Version 1.1-(mRECIST 1.1) GIST specific, or death due to any cause. Per mRECIST 1.1, progression was defined using mRECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years)

• Progression Free Survival (PFS) in the All Patient (AP) Intent to Treat (ITT) Population

  PFS is defined as the interval between the date of randomization and the earliest documented evidence of disease progression based on the independent radiologic review using modified RECIST Version 1.1-(mRECIST 1.1) Gastrointestinal stromal tumor (GIST) specific, or death due to any cause. Per mRECIST 1.1, progression was defined using mRECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years)

Secondary Outcomes (4)

• Objective Response Rate (ORR) in the KIT Exon 11 Intent to Treat (ITT) Population Population

  From confirmed CR or PR to disease progression (up to 1.74 years)

• Objective Response Rate (ORR) in the All Patient (AP) Intent to Treat (ITT) Population

  From confirmed CR or PR to disease progression (up to 1.74 years)

• Overall Survival (OS) in the KIT Exon 11 Intent to Treat (ITT) Population

  From date of randomization until death due to any cause (up to 3.33 years)

• Overall Survival (OS) in the All Patient (AP) Intent to Treat (ITT) Population

  From date of randomization until death due to any cause (up to 3.33 years)

Study Arms (2)

Ripretinib

EXPERIMENTAL

Ripretinib (150 mg) once a day continuous dosing for 6-week (42 days) cycles

Drug: Ripretinib

Sunitinib

ACTIVE COMPARATOR

Sunitinib (50 mg) once a day in 6-week (42 days) cycles with 4 weeks continuous dosing followed by 2 week break.

Drug: Sunitinib

Interventions

Ripretinib DRUG

Oral KIT/PDGFRA kinase inhibitor

Also known as: DCC-2618

Ripretinib

Sunitinib DRUG

Oral receptor tyrosine kinase (RTK) inhibitor

Also known as: Sutent

Sunitinib

Eligibility Criteria

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

You may qualify if:

• Patients ≥ 18 years of age at the time of informed consent.
• Histologic diagnosis of GIST and must be able to provide an archival tumor tissue sample, otherwise, a fresh biopsy is required.
• Molecular pathology report must be available. If molecular pathology report is not available or insufficient, an archival tumor tissue sample or fresh biopsy is required for mutation status confirmation by the central laboratory prior to randomization.
• Patients must have progressed on imatinib or have documented intolerance to imatinib.
• Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of ≤ 2 at screening.
• Female patients of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening and negative pregnancy test at Cycle 1 Day 1 prior to the first dose of study drug.
• Patients of reproductive potential must agree to follow the contraception requirements outlined in the study protocol.
• Patients must have at least 1 measurable lesion according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1 (non nodal lesions must be ≥ 1.0 cm in the long axis or ≥ double the slice thickness in the long axis) within 21 days prior to the first dose of study drug.
• Adequate organ function and bone marrow reserve as indicated by the central laboratory assessments performed at screening.
• Resolution of all toxicities from prior therapy to ≤ Grade 1 (or patient baseline) within 1 week prior to the first dose of study drug (excluding alopecia and ≤ Grade 3 clinically asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).
• The patient is capable of understanding and complying with the protocol and the patient has signed the informed consent document. Signed informed consent form (ICF) must be obtained before any study-specific procedures are performed and the patient must agree to not participate in any other interventional clinical trial while on treatment in this clinical trial. Participation in a noninterventional study (including observational studies) is permitted.

You may not qualify if:

• Treatment with any other line of therapy in addition to imatinib for advanced GIST. Imatinib-containing combination therapy in the first-line setting is not allowed.
• Patients with a prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of this clinical trial are not eligible.
• Patient has known active central nervous system metastases.
• New York Heart Association class II-IV heart disease, myocardial infarction within 6 months of cycle 1 day 1, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure.
• Left ventricular ejection fraction (LVEF) \< 50% at screening.
• Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before the first dose of study drug.
• Venous thrombotic events (e.g. deep vein thrombosis) or pulmonary arterial events (e.g. pulmonary embolism) within 1 month before the first dose of study drug. Patients on stable anticoagulation therapy for at least one month are eligible.
• lead ECG demonstrating QT interval corrected (QTc) by Fridericia's formula \> 450 ms in males or \> 470 ms in females at screening or history of long QTc syndrome
• Use of known substrates or inhibitors of breast cancer resistance protein (BCRP) transporters within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug.
• Major surgeries (e.g. abdominal laparotomy) within 4 weeks of the first dose of study drug. All major surgical wounds must be healed and free of infection or dehiscence before the first dose of study drug.
• Any other clinically significant comorbidities.
• Known human immunodeficiency virus or hepatitis C infection only if the patient is taking medications that are excluded per protocol, active hepatitis B, or active hepatitis C infection.
• If female, the patient is pregnant or lactating.
• Known allergy or hypersensitivity to any component of the study drug.
• Gastrointestinal abnormalities including but not limited to:

Sponsors & Collaborators

• Deciphera Pharmaceuticals, LLC: lead

Study Sites (121)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259, United States

Location

University of California San Diego Medical Center

La Jolla, California, 92103, United States

Location

UCLA Hematology Oncology Center - Main Site

Los Angeles, California, 90024, United States

Location

Stanford Medicine

Stanford, California, 94305, United States

Location

University of Colorado Hospital - Anschutz Cancer Pavillion

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80220, United States

Location

Smilow Cancer Hospital at Yale

New Haven, Connecticut, 06511, United States

Location

Washington Cancer Institute at MedStar Washington Hospital Center

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

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176, United States

Location

Orlando Health UF Health Cancer Center

Orlando, Florida, 32806, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30332, United States

Location

Georgia Cancer Specialists

Sandy Springs, Georgia, 30342, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

IU Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

Norton Cancer Institute, Audubon Hospital Campus

Louisville, Kentucky, 40241, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 43606, United States

Location

The Monter Cancer Center

Lake Success, New York, 11042, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center-Montefiore Medical Park

The Bronx, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

Location

University of Toledo

Toledo, Ohio, 43606, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health & Science University Center for Health and Healing

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Henry-Joyce Cancer Clinic

Nashville, Tennessee, 37232, United States

Location

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Froedtert Hospital-Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Sanatorio Allende

Córdoba, Córdoba Province, X5000JHQ, Argentina

Location

Instituto Medicao Especializado Alexander Fleming

Buenos Aires, Argentina

Location

Border Medical Oncology Research Unit

Albury, New South Wales, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Location

Ashford Cancer Centre Research

Kurralta Park, South Australia, 5037, Australia

Location

Ashford Cancer Centre Research

Kurralta Park, South Australia, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Princess Alexandara Hospital

Woolloongabba, Australia

Location

Institut Jules Bordet

Brussels, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Location

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C1, Canada

Location

Hopital Maisonneuve-Rosemont

Québec, Canada

Location

Clinica San Carlos de Apoquindo Red Salud UC Christs

Santiago, Chile

Location

Fakultni nemocnice v Motole

Prague, Czechia

Location

Institut Bergonnié

Bordeaux, France

Location

Centre Georges François Leclerc

Dijon, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Hopital La Timone

Marseille, France

Location

IPC

Marseille, France

Location

IGR

Paris, France

Location

CHU Poitiers-Hopital la Miletrie

Poitiers, France

Location

ICO - Site René Gauducheau

Saint-Herblain, France

Location

HELIOS Klinikum Berlin-Buch

Berlin, Germany

Location

Technische Universitat Dresden

Dresden, Germany

Location

West German Cancer Center

Essen, Germany

Location

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, Hungary

Location

Debreceni Egyetem

Debrecen, Hungary

Location

Shamir Medical Center (Assaf Harofeh)

Be’er Ya‘aqov, Israel

Location

Rabin Medical Cente

Petah Tikva, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, Italy

Location

stituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori

Meldola, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

IOV - Istituto Oncologico Veneto IRCCS

Padua, Italy

Location

Universita degli Studi di Palermo

Palermo, Italy

Location

Università Campus Bio-Medico di Roma

Rome, Italy

Location

Antoni van Leeuwenhoek

Amsterdam, Netherlands

Location

The Netherlands Cancer Institute

Amsterdam, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Leiden University Medical Centre

Leiden, Netherlands

Location

Oslo University Hospital

Oslo, Norway

Location

Centrum Onkologii-Instytut im. M. Sklodowskiej Curie

Warsaw, Poland

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Ajou University Hospital

Suwon, South Korea

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital de Basurto

Bilbao, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Clinico San Carlos

Madrid, Spain

Location

Hospital Universitario HM Madrid Sanchinarro

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Instituto Valenciano de Oncología,

Valencia, Spain

Location

Complejo Hospitalario Universitario de Vigo

Vigo, Spain

Location

Karolinska universitetssjukhuset

Solna, Sweden

Location

Centre Hospitalier Universitaire Vaudois, Fondation du Centre Pluridisciplinaire d'Oncologi

Lausanne, Switzerland

Location

Universitaetsspital Zuerich, Klinik fuer Onkologie

Zurich, Switzerland

Location

Chang Gung Memorial Hospital

Linkou District, Taoyuan County, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital,

Kaohsiung City, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

National Chen Kung University Hospital

Tainan, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

St James's University Hospital

Leeds, United Kingdom

Location

Royal Marsden Hospital - Fulham

London, United Kingdom

Location

University College London Hospitals

London, United Kingdom

Location

Weston Park Hospital

Sheffield, United Kingdom

Location

Related Publications (5)

• Heinrich MC, Blay JY, Gelderblom H, George S, Schoffski P, von Mehren M, Zalcberg JR, Jones RL, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Boye K, Goldstein D, Sanchez C, Siontis BL, Cox P, Davis E, Sherman ML, Ruiz-Soto R, Bauer S. Updated Overall Survival and Long-Term Safety With Ripretinib Versus Sunitinib in Patients With GI Stromal Tumor: Final Overall Survival Analysis From INTRIGUE. J Clin Oncol. 2025 Jul 10;43(20):2239-2244. doi: 10.1200/JCO-24-02818. Epub 2025 May 23.

  PMID: 40408605 DERIVED

• Heinrich MC, Jones RL, George S, Gelderblom H, Schoffski P, von Mehren M, Zalcberg JR, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Siontis BL, Goldstein D, Boye K, Sanchez C, Steeghs N, Rutkowski P, Druta M, Serrano C, Somaiah N, Chi P, Reichmann W, Sprott K, Achour H, Sherman ML, Ruiz-Soto R, Blay JY, Bauer S. Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial. Nat Med. 2024 Feb;30(2):498-506. doi: 10.1038/s41591-023-02734-5. Epub 2024 Jan 5.

  PMID: 38182785 DERIVED

• Gelderblom H, Jones RL, Blay JY, George S, von Mehren M, Zalcberg JR, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Siontis BL, Goldstein D, Boye K, Sanchez C, Steeghs N, Rutkowski P, Druta M, Serrano C, Somaiah N, Chi P, Harrow B, Becker C, Reichmann W, Sherman ML, Ruiz-Soto R, Heinrich MC, Bauer S; INTRIGUE investigators. Patient-reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after treatment with imatinib in INTRIGUE, a phase 3, open-label study. Eur J Cancer. 2023 Oct;192:113245. doi: 10.1016/j.ejca.2023.113245. Epub 2023 Jul 20.

  PMID: 37598656 DERIVED

• Bauer S, Jones RL, Blay JY, Gelderblom H, George S, Schoffski P, von Mehren M, Zalcberg JR, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Su Y, Meade J, Wang T, Sherman ML, Ruiz-Soto R, Heinrich MC. Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Dec 1;40(34):3918-3928. doi: 10.1200/JCO.22.00294. Epub 2022 Aug 10.

  PMID: 35947817 DERIVED

• Nemunaitis J, Bauer S, Blay JY, Choucair K, Gelderblom H, George S, Schoffski P, Mehren MV, Zalcberg J, Achour H, Ruiz-Soto R, Heinrich MC. Intrigue: Phase III study of ripretinib versus sunitinib in advanced gastrointestinal stromal tumor after imatinib. Future Oncol. 2020 Jan;16(1):4251-4264. doi: 10.2217/fon-2019-0633. Epub 2019 Nov 22.

  PMID: 31755321 DERIVED

Related Links

• Deciphera Company Website

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

ripretinib; Sunitinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; 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

Results Point of Contact

• Title: INTRIGUE Clinical Team
• Organization: Deciphera Pharmaceuticals, LLC

clinicaltrials@deciphera.com

781-209-6400

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 13, 2018
• First Posted: September 17, 2018
• Study Start: February 8, 2019
• Primary Completion: September 1, 2021
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 5, 2026
• Results First Posted: January 2, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2); HU (2); US (43); IT (6); KR (4); AR (2); BE (2); IL (3); PL (1); TW (5); CA (6); CL (1); ES (12); SG (1); DE (3); SE (1); FR (9); NO (1); NL (4); CZ (1); AU (7); GB (5)