A Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With Specific KIT Exon Mutations Who Were Previously Treated With Imatinib

NCT05734105 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: DCC-2618-03-0032022-503058-37-00
• Study Type: interventional
• Target: 54
• Locations: 15 countries
• Sites: 70

Brief Summary

This is a Phase 3, 2-arm, randomized, open-label, global, multicenter study comparing the efficacy of ripretinib to sunitinib in participants with GIST who progressed on first-line treatment with imatinib, harbor co-occurring KIT exons 11+17/18 mutations, and are without KIT exon 9, 13, or 14 mutations. Upon disease progression as determined by an independent radiologic review, participants randomized to sunitinib will be given the option to either crossover to receive ripretinib 150 mg QD or discontinue sunitinib.

Conditions

GIST

Keywords

advanced gastrointestinal tumors; gastrointestinal stromal tumors; imatinib; ripretinib

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  The time from randomization until documented progressive disease (PD) based on IRR per mRECIST or death due to any cause, whichever occurs first.

  Up to end of treatment; up to approximately 48 months

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  Up to end of treatment; up to approximately 48 months

• Overall Survival (OS)

  Up to approximately 48 months

Study Arms (2)

Ripretinib

EXPERIMENTAL

150 mg QD of ripretinib (3×50 mg tablets) will be dosed continuously in repeated 42-day cycles.

Drug: Ripretinib

Sunitinib

ACTIVE COMPARATOR

50 mg QD of sunitinib (4×12.5 mg capsules) will be dosed in 42-day cycles. Sunitinib will be given continuously for 4 weeks with a 2-week break.

Drug: Sunitinib

Interventions

Ripretinib DRUG

50 mg tablets

Also known as: QINLOCK, DCC-2618

Ripretinib

Sunitinib DRUG

12.5 mg tablets

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:

• Male or female ≥18 years of age.
• Histologic diagnosis of GIST with co-occurring KIT exons 11+17/18 mutations confirmed by ctDNA sample.
• Participants must have advanced GIST and radiologic progression on imatinib treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2 at screening.
• Female participants of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug.
• Participants of reproductive potential must agree to follow contraception requirements.
• Participants must have at least 1 measurable lesion according to mRECIST v1.1 within 21 days prior to the first dose of study drug.
• Adequate organ function and bone marrow reserve based on laboratory assessments performed at screening.

You may not qualify if:

• History of KIT exon 9 mutation or detection of KIT exon 9, 13, or 14 mutations in a ctDNA sample.
• 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.
• Use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A prior to the first dose of study drug, and consumption of grapefruit or grapefruit juice within 14 days prior to the first dose of study drug.
• Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug.
• Known human immunodeficiency virus or hepatitis C infection only if the participant is taking medications that are excluded per protocol, acute or chronic hepatitis B, or acute or chronic hepatitis C infection.
• Gastrointestinal abnormalities including, but not limited to:
• inability to take oral medication
• malabsorption syndromes
• requirement for intravenous alimentation
• Any active bleeding excluding hemorrhoidal or gum bleeding.

Sponsors & Collaborators

• Deciphera Pharmaceuticals, LLC: lead

Study Sites (70)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Northwell Health Cancer Institute/ R.J. Zuckerberg Cancer Center

New York, New York, 11042, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Alfred Health

Melbourne, Victoria, 3004, Australia

Location

INCA - Instituto Nacional de Cancer

Rio de Janeiro, Rio de Janeiro, 20231, Brazil

Location

CEPEN - Centro de Pesquisa e Ensino em Saude de Santa Catarina

Florianópolis, Santa Catarina, 88034-000, Brazil

Location

Hospital de Cancer de Barretos - Fundacao Pio XII

Barretos, São Paulo, 14748-400, Brazil

Location

Hospital Sirio-Libanes

São Paulo, São Paulo, 01308, Brazil

Location

Hospital 9 de Julho

São Paulo, São Paulo, 01409-002, Brazil

Location

AC Camargo Câncer Center

São Paulo, São Paulo, 01509-900, Brazil

Location

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

University Health Network, Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Clínica San Carlos De Apoquindo Red Salud UC Christus

Las Condes, RM, 7620002, Chile

Location

Centro de Oncología de Precisión

Santiago, RM, 7550000, Chile

Location

CHU Dijon

Dijon, Bourgogone, 21079, France

Location

Centre Eugène Marquis

Rennes, Ille et Vilaine, 35000, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Helios Klinikum Berlin-Buch

Berlin, Germany

Location

University Hospital Essen (Universitätsklinikum Essen)

Essen, 45147, Germany

Location

Heidelberg University Hospital

Heidelberg, 69120, Germany

Location

Universitares Krebszentrum Leipzig

Leipzig, 04103, Germany

Location

Istituto Nazionale Tumori IRCCS Fondazione "G Pascale"

Naples, Napoli, 80131, Italy

Location

U.O.C. Oncologia Medica

Palermo, Palermo, 90127, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, 40138, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Oncologico Veneto-IOV IRCCS

Padua, 35128, Italy

Location

Università Campus Bio-Medico di Roma

Roma, 00128, Italy

Location

IRCCS Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

UMC Groningen

Groningen, 9713, Netherlands

Location

LUMC

Leiden, 2333 ZA, Netherlands

Location

Oslo University Hospital

Oslo, Norway, 0379, Norway

Location

Narodowy Instytut Onkologii Im . Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, Warszawa, 02-781, Poland

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitario Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

Location

Complejo Hospitalario Universitario de Vigo - Hospital Alvaro Cunqueiro

Vigo, Pontevedra, 36312, Spain

Location

Instituto Valenciano de Oncologia - IVO

Valencia, Valencia, 46009, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario Centra de Asturias

Oviedo, 33011, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

The Royal Marsden Hospital NHS Foundation Trust

London, Greater London, SW3 6JJ, United Kingdom

Location

St. James University Hospital

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Related Publications (1)

• George S, Blay JY, Chi P, Jones RL, Serrano C, Somaiah N, Gelderblom H, Zalcberg JR, Reichmann W, Sprott K, Cox P, Sherman ML, Ruiz-Soto R, Heinrich MC, Bauer S. The INSIGHT study: a randomized, Phase III study of ripretinib versus sunitinib for advanced gastrointestinal stromal tumor with KIT exon 11 + 17/18 mutations. Future Oncol. 2024;20(27):1973-1982. doi: 10.1080/14796694.2024.2376521. Epub 2024 Sep 4.

  PMID: 39229786 DERIVED

Related Links

• INSIGHT Patient Website
• INSIGHT Physician 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

Study Officials

• Clinical Team

  Deciphera Pharmaceuticals, LLC

  STUDY DIRECTOR

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: February 8, 2023
• First Posted: February 17, 2023
• Study Start: December 13, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

AU (2); NO (1); US (20); BR (6); CL (2); ES (8); NL (2); PL (1); DE (4); FR (5); GB (2); TW (3); KR (3); IT (7); CA (4)