GISTPhase 1/2LONGISTNCT07096609
Lenvatinib After Progression on Imatinib, Sunitinib, and Regorafenib for GIST Patients
A Phase 1/2 study testing Lenvatinib Capsules in people with GIST, run by Asan Medical Center at 1 site in South Korea.
Trial summary
The aim of this study is to evaluate the safety and efficacy of lenvatinib in patients with metastatic or advanced GIST who have failed at least imatinib, sunitinib, and regorafenib treatment. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- GIST
- What is being tested?
- Lenvatinib Capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteSouth Korea
- Study dates
- 29 Oct 2025to 31 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 20 years at the time of providing written informed consent.
- Histologically confirmed metastatic and/or advanced (unresectable or recurrent) GIST with positivity for CD117(+), DOG-1(+), or harboring mutations in the KIT or PDGFRα genes.
- Documented failure of prior treatment with imatinib, sunitinib, and regorafenib due to disease progression and/or intolerance.
- Note: There is no limitation on the number of prior therapies. Prior use of other tyrosine kinase inhibitors (TKIs) or chemotherapy in combination with imatinib, sunitinib, or regorafenib is permitted.
- Disease progression is defined as:
- Increase in tumor size by ≥ 20% per mRECIST version 1.1
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- Emergence of unequivocal new lesions (excluding newly developed small cystic liver lesions within 6 months after initiation of TKI treatment)
- Appearance of new solid nodules within cystic masses
- Increase in the size of existing solid nodules within cystic masses (>20%)
- Intolerance to prior TKIs is defined as:
- Drug compliance <75% due to ≥ Grade 2 non-hematologic toxicity, despite dose reduction to one level below the standard dose (i.e., imatinib 300 mg/day; sunitinib 37.5 mg/day on a 4-week on/2-week off schedule or 25 mg/day on a continuous schedule; regorafenib 120 mg/day)
- Despite the same dose reduction as above, the occurrence of febrile neutropenia, Grade 4 neutropenia lasting more than 6 days, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3-4 or persistent ≥ Grade 2 non-hematologic toxicity deemed intolerable
- ECOG performance status of 0-2.
- All toxicities from previous treatments must have recovered to Grade 0 or 1 as per NCI-CTCAE version 5.0.
- At least one measurable lesion as defined by mRECIST version 1.1.
- Adequate bone marrow, liver, renal, and other organ function:
- Absolute neutrophil count (ANC) ≥ 1,500/mm³
- Platelets ≥ 100,000/mm³
- Hemoglobin ≥ 8.0 g/dL
- Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
- AST/ALT ≤ 2.5 × ULN (or ≤ 5 × ULN in case of liver metastases)
- Serum creatinine ≤ 1.5 × ULN
- Life expectancy ≥ 12 weeks
- A washout period equivalent to at least 4 times the half-life of previous TKI or chemotherapeutic agents is required(Imatinib and regorafenib: ≥ 1 week; Sunitinib: ≥ 2 weeks)
- Signed written informed consent
Who cannot join
- Women of childbearing potential who are pregnant or breastfeeding
- Women or men unwilling to use effective contraception during the study treatment period and for 6 months after the last dose of the investigational drug
- All participants (both men and women) must use barrier contraception during the treatment period and for at least 1 month after the final dose
- Women of childbearing potential are defined as sexually mature females who have not undergone hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., had menstruation within the past 12 months)
- History of any of the following within 6 months prior to enrollment: myocardial infarction, severe or unstable angina, coronary or peripheral artery bypass surgery, congestive heart failure classified as NYHA Class III or IV, stroke or transient ischemic attack (TIA), or clinically significant arrhythmias requiring treatment
- Uncontrolled active infection
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- Diabetes mellitus with clinically significant signs of peripheral vascular disease
- Acute or chronic liver disease, or any chronic hepatic disorder (patients with stable chronic hepatitis B are eligible)
- Uncontrolled gastrointestinal toxicities greater than Grade 2 according to NCI-CTCAE (e.g., nausea, diarrhea, vomiting)
- Any severe acute or chronic medical or psychiatric condition, or clinically significant abnormal laboratory finding, that may increase the risk associated with study participation or investigational drug administration, or interfere with the interpretation of study results, as determined by the investigator
- History of life-threatening bleeding or any Grade 3 or 4 bleeding event requiring transfusion, endoscopic intervention, or surgical procedure within 3 months prior to initiation of study drug
- Treatment with clinically significant systemic anticoagulant or antithrombotic agents within 7 days prior to consent that, in the opinion of the investigator, may put the patient at risk. Use of aspirin is permitted up to a maximum dose of 325 mg/day
- Uncontrolled hypertension (blood pressure ≥ 140/90 mmHg) that is not adequately managed with medication, or change in antihypertensive regimen within 7 days prior to consent; such patients may be at increased risk during VEGF inhibitor therapy
- Major surgery, significant trauma (e.g., bone fracture), or non-healed wounds within 3 weeks prior to consent (procedures such as catheter insertion are not considered major)
- History of other significant cardiovascular or vascular conditions within 6 months prior to consent that, in the opinion of the investigator, may place the patient at risk during VEGF inhibitor therapy, including but not limited to hypertensive crisis, hypertensive encephalopathy, stroke, transient ischemic attack (TIA), or clinically significant peripheral vascular disease
- Clinically significant glomerulonephritis, biopsy-proven tubulointerstitial nephritis, crystal nephropathy, or other history of renal failure
- Known diagnosis of HIV infection (HIV testing is not mandatory)
- History of another primary malignancy that has recently become clinically significant or currently requires active intervention
- Evidence of brain metastasis on radiological imaging (e.g., CT or MRI) in patients presenting with symptoms suggestive of central nervous system involvement
- History of alcohol or substance abuse disorder
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Asan Medical Center
Seoul, 05505
Jaewon Hyung, 82-2-3010-1464, musicine123@gmail.com
Hyung-Don kim, kimhdmd@amc.seoul.kr
About this study
Official title: A Single-center, Single-arm Phase II Study to Evaluate the Efficacy and Safety of Lenvatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) Who Have Failed Treatment With Imatinib, Sunitinib, and Regorafenib
The aim of this study is to evaluate the safety and efficacy of lenvatinib in patients with metastatic or advanced GIST who have failed at least imatinib, sunitinib, and regorafenib treatment.
Read the detailed description
The discovery of KIT gene mutations and the development of the KIT tyrosine kinase inhibitor imatinib (Glivec™, Novartis) have significantly improved the survival rates of patients with advanced and metastatic gastrointestinal stromal tumors (GIST). More recently, sunitinib (Sutene™, Pfizer) and regorafenib (Stivarga®, Bayer) have been proven effective as second- and third-line therapies, respectively, for patients who have failed imatinib treatment. However, nearly all patients eventually develop resistance to first-line imatinib, second-line sunitinib, and third-line regorafenib, resulting in disease progression. Although ripretinib, a fourth-line treatment, has demonstrated an improvement in progression-free survival to 6.3 months compared to placebo in the phase III INVICTUS trial, it remains inaccessible in many regions, including Korea, limiting its clinical application. Therefore, there is an urgent need for new therapeutic alternatives after imatinib, sunitinib, and regorafenib in clinical practice.
Lenvatinib is a multi-targeted tyrosine kinase inhibitor with potent anti-angiogenic activity, primarily targeting VEGFR1-3 with IC₅₀ values of 4.7, 3.0, and 2.3 nmol/L, respectively. It also exhibits inhibitory activity against c-KIT (IC₅₀: 85 nmol/L) and PDGFR-α (IC₅₀: 29 nmol/L). Pharmacokinetically, lenvatinib is rapidly absorbed with a bioavailability of 85% and has an elimination half-life of approximately 28 hours. The LENVAGIST study, presented at ESMO 2024, was a phase II randomized, placebo-controlled trial that demonstrated the significant clinical activity of lenvatinib in patients with advanced GIST who had progressed after treatment with imatinib and sunitinib. In this study, the 4-month progression-free survival rate was 39% in the lenvatinib group versus 11% in the placebo group (HR 0.44; 95% CI 0.27-0.71; p=0.0008), and the median overall survival was 14.4 months versus 8.7 months, respectively. Treatment-related grade ≥3 adverse events were observed in 56.4% of patients in the lenvatinib group and 18.4% in the placebo group.
- Conditions
- GIST
- Being tested
- Lenvatinib Capsules
- Keywords
- GIST, Lenvatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lenvatinib CapsulesDrug
Lenvatinib will be administered orally once daily at a dose of 12 mg (for patients weighing ≥ 60 kg) or 8 mg (for patients weighing < 60 kg). Each treatment cycle consists of 4 weeks (i.e., 28 days).
| Study group | Role | What they receive |
|---|---|---|
| Lenvatinib treatment | Experimental | Not described Receives: Drug: Lenvatinib Capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
DCR(disease control rate) at 12 weeks
To evaluate the disease control rate (DCR; defined as the sum of partial responses and stable disease) at 12 Weeks
Measured: at 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2025
- Study start29 Oct 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GISTStudies of the same condition, open and under way.
- More trials run by Asan Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jaewon Hyung, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07096609
- Sponsor's protocol ID
- AMC2502
- Acronym
- LONGIST
- Status last verified
- Apr 2026
- First submitted
- 24 Jul 2025
- Last updated
- 3 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Single-arm Phase II Study to Evaluate the Efficacy and Safety of Lenvatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) Who Have Failed Treatment With Imatinib, Sunitinib, and Regorafenib
- ClinicalTrials.gov ID
- NCT07096609
- Acronym / sponsor ID
- LONGIST / AMC2502
- Conditions
- GIST
- Keywords
- GIST, Lenvatinib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Study start
- 29 Oct 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 31 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to evaluate the safety and efficacy of lenvatinib in patients with metastatic or advanced GIST who have failed at least imatinib, sunitinib, and regorafenib treatment.
Detailed description
The discovery of KIT gene mutations and the development of the KIT tyrosine kinase inhibitor imatinib (Glivec™, Novartis) have significantly improved the survival rates of patients with advanced and metastatic gastrointestinal stromal tumors (GIST). More recently, sunitinib (Sutene™, Pfizer) and regorafenib (Stivarga®, Bayer) have been proven effective as second- and third-line therapies, respectively, for patients who have failed imatinib treatment. However, nearly all patients eventually develop resistance to first-line imatinib, second-line sunitinib, and third-line regorafenib, resulting in disease progression. Although ripretinib, a fourth-line treatment, has demonstrated an improvement in progression-free survival to 6.3 months compared to placebo in the phase III INVICTUS trial, it remains inaccessible in many regions, including Korea, limiting its clinical application. Therefore, there is an urgent need for new therapeutic alternatives after imatinib, sunitinib, and regorafenib in clinical practice.
Lenvatinib is a multi-targeted tyrosine kinase inhibitor with potent anti-angiogenic activity, primarily targeting VEGFR1-3 with IC₅₀ values of 4.7, 3.0, and 2.3 nmol/L, respectively. It also exhibits inhibitory activity against c-KIT (IC₅₀: 85 nmol/L) and PDGFR-α (IC₅₀: 29 nmol/L). Pharmacokinetically, lenvatinib is rapidly absorbed with a bioavailability of 85% and has an elimination half-life of approximately 28 hours. The LENVAGIST study, presented at ESMO 2024, was a phase II randomized, placebo-controlled trial that demonstrated the significant clinical activity of lenvatinib in patients with advanced GIST who had progressed after treatment with imatinib and sunitinib. In this study, the 4-month progression-free survival rate was 39% in the lenvatinib group versus 11% in the placebo group (HR 0.44; 95% CI 0.27-0.71; p=0.0008), and the median overall survival was 14.4 months versus 8.7 months, respectively. Treatment-related grade ≥3 adverse events were observed in 56.4% of patients in the lenvatinib group and 18.4% in the placebo group.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenvatinib treatment | Experimental | Drug: Lenvatinib Capsules |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Age ≥ 20 years at the time of providing written informed consent.
- Histologically confirmed metastatic and/or advanced (unresectable or recurrent) GIST with positivity for CD117(+), DOG-1(+), or harboring mutations in the KIT or PDGFRα genes.
- Documented failure of prior treatment with imatinib, sunitinib, and regorafenib due to disease progression and/or intolerance.
- ECOG performance status of 0-2.
- All toxicities from previous treatments must have recovered to Grade 0 or 1 as per NCI-CTCAE version 5.0.
Key exclusion criteria (20 listed)
- Women of childbearing potential who are pregnant or breastfeeding
- Women or men unwilling to use effective contraception during the study treatment period and for 6 months after the last dose of the investigational drug
- All participants (both men and women) must use barrier contraception during the treatment period and for at least 1 month after the final dose
- Women of childbearing potential are defined as sexually mature females who have not undergone hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., had menstruation within the past 12 months)
- History of any of the following within 6 months prior to enrollment: myocardial infarction, severe or unstable angina, coronary or peripheral artery bypass surgery, congestive heart failure classified as NYHA Class III or IV, stroke or transient ischemic attack (TIA), or clinically significant arrhythmias requiring treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lenvatinib CapsulesLenvatinib will be administered orally once daily at a dose of 12 mg (for patients weighing ≥ 60 kg) or 8 mg (for patients weighing < 60 kg). Each treatment cycle consists of 4 weeks (i.e., 28 days). | Drug | Lenvatinib treatment |
Primary outcome
DCR(disease control rate) at 12 weeks
Time frame: at 12 weeks
To evaluate the disease control rate (DCR; defined as the sum of partial responses and stable disease) at 12 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lenvatinib Capsules in people with GIST, run by Asan Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jaewon Hyung (82-2-3010-1464, musicine123@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DCR(disease control rate) at 12 weeks (time frame: at 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2026.