NCT03673501 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-02-05

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).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: 1. Patients ≥ 18 years of age at the time of informed consent. 2. Histologic diagnosis of GIST and must be able to provide an archival tumor tissue sample, otherwise, a fresh biopsy is required. 3. 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. 4. Patients must have progressed on imatinib or have documented intolerance to imatinib. 5. Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of ≤ 2 at screening. 6. 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. 7. Patients of reproductive potential must agree to follow the contraception requirements outlined in the study protocol. 8. 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. 9. Adequate organ function and bone marrow reserve as indicated by the central laboratory assessments performed at screening. 10. 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). 11. 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. Exclusion Criteria: 1. 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. 2. 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. 3. Patient has known active central nervous system metastases. 4. 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. 5. Left ventricular ejection fraction (LVEF) \< 50% at screening. 6. Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before the first dose of study drug. 7. 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. 8. 12-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 9. 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. 10. 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. 11. Any other clinically significant comorbidities. 12. 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. 13. If female, the patient is pregnant or lactating. 14. Known allergy or hypersensitivity to any component of the study drug. 15. Gastrointestinal abnormalities including but not limited to: * inability to take oral medication * malabsorption syndromes * requirement for intravenous (IV) alimentation 16. Any active bleeding excluding hemorrhoidal or gum bleeding.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Ripretinib (150 mg) once a day continuous dosing for 6-week (42 days) cycles
intervention Names
Drug: Ripretinib
label
Ripretinib
type
EXPERIMENTAL
description
Sunitinib (50 mg) once a day in 6-week (42 days) cycles with 4 weeks continuous dosing followed by 2 week break.
intervention Names
Drug: Sunitinib
label
Sunitinib
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Ripretinib
description
Oral KIT/PDGFRA kinase inhibitor
name
Ripretinib
other Names
DCC-2618
type
DRUG
arm Group Labels
Sunitinib
description
Oral receptor tyrosine kinase (RTK) inhibitor
name
Sunitinib
other Names
Sutent
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 453
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Progression Free Survival (PFS) in the KIT Exon 11 Intent to Treat (ITT) Population
time Frame
From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years)
description
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.
measure
Progression Free Survival (PFS) in the All Patient (AP) Intent to Treat (ITT) Population
time Frame
From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years)

secondary Outcomes

description
ORR was defined as the proportion of patients with confirmed complete response (CR) + confirmed partial response (PR) based on independent radiologic review using modified RECIST (mRECIST) criteria as best overall response. Per mRECIST 1.1 criteria, complete response is defined as disappearance of all target lesions; partial response is defined as \>=30% decrease in the sum of the longest diameter of target lesions.
measure
Objective Response Rate (ORR) in the KIT Exon 11 Intent to Treat (ITT) Population Population
time Frame
From confirmed CR or PR to disease progression (up to 1.74 years)
description
ORR was defined as the proportion of patients with confirmed complete response (CR) + confirmed partial response (PR) based on independent radiologic review using modified RECIST (mRECIST) criteria as best overall response. Per mRECIST 1.1 criteria, complete response is defined as disappearance of all target lesions; partial response is defined as \>=30% decrease in the sum of the longest diameter of target lesions.
measure
Objective Response Rate (ORR) in the All Patient (AP) Intent to Treat (ITT) Population
time Frame
From confirmed CR or PR to disease progression (up to 1.74 years)
description
OS was defined as the time from the date of randomization until death due to any cause.
measure
Overall Survival (OS) in the KIT Exon 11 Intent to Treat (ITT) Population
time Frame
From date of randomization until death due to any cause (up to 3.33 years)
description
OS was defined as the time from the date of randomization until death due to any cause.
measure
Overall Survival (OS) in the All Patient (AP) Intent to Treat (ITT) Population
time Frame
From date of randomization until death due to any cause (up to 3.33 years)

Full study description

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).

Source references

references

citation
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
type
DERIVED
citation
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pmid
38182785
type
DERIVED
citation
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citation
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
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pmid
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type
DERIVED