GIST - Gastrointestinal Stromal TumorPhase 2NCT07559864
Comparing Regorafenib Combined With Envafolimab to Physician's Choice in Patients With Metastatic Gastrointestinal Stromal Tumors Harboring KIT Exon 17 Mutations Refractory to Standard Treatment
A Phase 2 study testing physician-selected treatment and Regorafenib + Envafolimab in people with GIST - Gastrointestinal Stromal Tumor and KIT Gene Mutation, run by Jian Li at 1 site in China.
Trial summary
Gastrointestinal stromal tumors (GISTs) are mostly driven by c-kit or PDGFRA mutations, and commonly occur in the stomach and small intestine. Targeted therapy is the mainstay for advanced metastatic GISTs, but there is a lack of effective regimens after drug resistance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GIST - Gastrointestinal Stromal Tumor, KIT Gene Mutation
- What is being tested?
- physician-selected treatment and Regorafenib + Envafolimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 14 Jul 2025to 1 Jun 2027
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged ≥ 18 years, regardless of gender;
- Confirmed as gastrointestinal stromal tumor by histopathological examination;
- Having at least one measurable target lesion meeting the criteria of mRECIST v1.1 (non-lymph node lesions with a long axis ≥ 1.0 cm or a long axis ≥ the thickness of 2 slides); imaging assessment should be performed within 14 days before the first medication;
- Disease progression or intolerance after treatment with imatinib, sunitinib, regorafenib, or ripretinib;
- Primary or secondary KIT exon 17 mutation detected by genetic testing;
- Sufficient organ and bone marrow function, defined as follows: Blood routine: Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; platelet count (PLT) ≥ 75×10⁹/L; hemoglobin (HGB) ≥ 9.0 g/dL. No use of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), red blood cell transfusion, or platelet transfusion within 14 days before the examination; Liver and kidney function: For subjects without liver metastasis, serum total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN. For subjects with liver metastasis: TBIL ≤ 1.5×ULN; ALT and AST ≤ 5×ULN. Renal function: Serum creatinine (Scr) ≤ 1.5×ULN; Sufficient coagulation function, defined as international normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5×ULN; if the subject is receiving anticoagulant therapy, it is acceptable as long as PT is within the range specified for the anticoagulant drug;
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- Provide 15 paraffin-embedded tissue sections before enrollment for immune microenvironment detection;
- ECOG PS score of 0-2;
- Signed informed consent form.
Who cannot join
- A history of intolerance to regorafenib treatment, or previous receipt of immune checkpoint inhibitor therapy;
- Being in pregnancy or lactation;
- Those with an expected survival period of less than 3 months;
- Those who have undergone major surgery or suffered significant trauma within 4 weeks before the first blood collection during the screening period, or are expected to require major surgery during the study period;
- Patients with current active ulcers or gastrointestinal bleeding;
- A history of interstitial lung disease or non-infectious pneumonia; a history of active tuberculosis;
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- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
- Patients with clinically confirmed autoimmune diseases; those with positive HIV or HCV; those with HBV-DNA exceeding the laboratory normal range; those with acute CMV infection;
- Patients with clinically confirmed central nervous system metastases;
- Patients with other malignant tumors within 5 years;
- Immunosuppressed subjects, including those with known immunodeficiency; those currently receiving systemic steroid medications (except those who have used inhaled steroids recently or currently);
- Uncontrolled hypertension: After active antihypertensive treatment, three consecutive blood pressure measurements indicate systolic blood pressure ≥ 160 mmHg and diastolic blood pressure ≥ 100 mmHg;
- Subjects who, in the investigator's assessment, are unable or unwilling to comply with the requirements of the study protocol.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100101
Jian Li, MD, +86 010-88196561, oncogene@163.com
Jian Li, MD
About this study
Official title: A Phase II, Open-label, Multicenter, Randomized Controlled Clinical Trial Comparing Regorafenib Combined With Envafolimab to Physician's Choice in Patients With Metastatic Gastrointestinal Stromal Tumors Harboring KIT Exon 17 Mutations Refractory to Standard Treatment
Gastrointestinal stromal tumors (GISTs) are mostly driven by c-kit or PDGFRA mutations, and commonly occur in the stomach and small intestine. Targeted therapy is the mainstay for advanced metastatic GISTs, but there is a lack of effective regimens after drug resistance. Immune checkpoint inhibitors (ICIs) have limited efficacy as monotherapy, while tyrosine kinase inhibitor (TKI) drugs such as regorafenib can improve the immune microenvironment and exert a synergistic effect when combined with ICIs, with more significant efficacy especially in cases with kit exon 17 mutations. This study aims to explore the effectiveness of regorafenib combined with envafolimab in metastatic gastrointestinal stromal tumors with kit exon 17 mutations that have failed standard treatment.
Read the detailed description
This is a multicenter, prospective phase II clinical study aiming to explore the efficacy and safety of regorafenib combined with envafolimab in metastatic gastrointestinal stromal tumors (GIST) with KIT exon 17 mutations that have failed standard treatment, as well as to investigate the correlation between the immune microenvironment and the efficacy of immunotherapy.
The study will enroll patients with histologically confirmed advanced metastatic GIST harboring KIT exon 17 mutations, with at least one evaluable lesion. Patients will be randomized at a 1:1 ratio into two groups: the experimental group will receive regorafenib combined with envafolimab (regorafenib at a recommended dose of 120 mg orally once daily, administered for 3 weeks followed by 1 week off; envafolimab 200 mg subcutaneously injected once every 2 weeks); the control group will receive either re-challenge with one previously effective targeted agent or combination therapy with two agents selected based on the clinician's experience. Treatment will continue until disease progression, occurrence of intolerable toxicity, or voluntary withdrawal of the patient from the trial.
A total of 100 patients are planned to be enrolled. Enrolled patients will undergo imaging assessments at baseline and every 2 months during treatment.
- Being tested
- physician-selected treatment, Regorafenib + Envafolimab
- Keywords
- Gastrointestinal Stromal Tumor, Treatment, kit gene
- Medical subject headings
- Gastrointestinal Stromal Tumors, Piebaldism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
physician-selected treatmentDrug
physician-selected treatment
Regorafenib + EnvafolimabDrug
Regorafenib: 120mg, orally, qd, administered for 3 weeks followed by 1 week of rest.
Envafolimab: 200mg, subcutaneously injected, q21d.
| Study group | Role | What they receive |
|---|---|---|
| control group（physician-selected） | Active comparator | Physicians will make selections based on previous drug tolerance, genetic types, etc.: 1) Maintenance treatment with the original dose of previously effective TKIs: during the previous treatment, the patient had achieved at least stable disease (SD) or partial response (PR), with progression-free survival (PFS) exceeding 6 months and tolerable adverse reactions; 2) Combination therapy with two TKI targeted drugs: according to different action targets indicated by genetic testing of the patient's tissue or peripheral blood, different drugs will be selected for maintenance, or a combination of previously effective and well-tolerated drugs will be chosen, or combination therapy will be selected with reference to previous tolerance. Receives: Drug: physician-selected treatment |
| treatment group（Regorafenib + Envafolimab） | Experimental | Patients in the treatment group will receive regorafenib combined with envafolimab. Regorafenib: 120 mg, orally, once daily, administered for 3 weeks followed by 1 week of rest. Envafolimab: 200 mg, subcutaneously injected, once every 2 weeks. Receives: Drug: Regorafenib + Envafolimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival（PFS）
Defined as the time from date of study treatment to disease progression radiological/clinical or death due to any cause, whichever occurs first.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2026
- Study start14 Jul 2025
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GIST - Gastrointestinal Stromal TumorStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jian Li
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jian Li, Peking University Cancer Hospital & Institute
- Investigators
- Jian Li, MD, Study chair, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07559864
- Sponsor's protocol ID
- GIST006
- Status last verified
- Apr 2026
- First submitted
- 20 Apr 2026
- Last updated
- 30 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-label, Multicenter, Randomized Controlled Clinical Trial Comparing Regorafenib Combined With Envafolimab to Physician's Choice in Patients With Metastatic Gastrointestinal Stromal Tumors Harboring KIT Exon 17 Mutations Refractory to Standard Treatment
- ClinicalTrials.gov ID
- NCT07559864
- Acronym / sponsor ID
- GIST006
- Keywords
- Gastrointestinal Stromal Tumor, Treatment, kit gene
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Jian LiUniversity, hospital or other
- Study start
- 14 Jul 2025 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 30 Apr 2026 (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.
Gastrointestinal stromal tumors (GISTs) are mostly driven by c-kit or PDGFRA mutations, and commonly occur in the stomach and small intestine. Targeted therapy is the mainstay for advanced metastatic GISTs, but there is a lack of effective regimens after drug resistance. Immune checkpoint inhibitors (ICIs) have limited efficacy as monotherapy, while tyrosine kinase inhibitor (TKI) drugs such as regorafenib can improve the immune microenvironment and exert a synergistic effect when combined with ICIs, with more significant efficacy especially in cases with kit exon 17 mutations. This study aims to explore the effectiveness of regorafenib combined with envafolimab in metastatic gastrointestinal stromal tumors with kit exon 17 mutations that have failed standard treatment.
Detailed description
This is a multicenter, prospective phase II clinical study aiming to explore the efficacy and safety of regorafenib combined with envafolimab in metastatic gastrointestinal stromal tumors (GIST) with KIT exon 17 mutations that have failed standard treatment, as well as to investigate the correlation between the immune microenvironment and the efficacy of immunotherapy.
The study will enroll patients with histologically confirmed advanced metastatic GIST harboring KIT exon 17 mutations, with at least one evaluable lesion. Patients will be randomized at a 1:1 ratio into two groups: the experimental group will receive regorafenib combined with envafolimab (regorafenib at a recommended dose of 120 mg orally once daily, administered for 3 weeks followed by 1 week off; envafolimab 200 mg subcutaneously injected once every 2 weeks); the control group will receive either re-challenge with one previously effective targeted agent or combination therapy with two agents selected based on the clinician's experience. Treatment will continue until disease progression, occurrence of intolerable toxicity, or voluntary withdrawal of the patient from the trial.
A total of 100 patients are planned to be enrolled. Enrolled patients will undergo imaging assessments at baseline and every 2 months during treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| control group（physician-selected） | Active comparator | Drug: physician-selected treatmentPhysicians will make selections based on previous drug tolerance, genetic types, etc.: 1) Maintenance treatment with the original dose of previously effective TKIs: during the previous treatment, the patient had achieved at least stable disease (SD) or partial response (PR), with progression-free survival (PFS) exceeding 6 months and tolerable adverse reactions; 2) Combination therapy with two TKI targeted drugs: according to different action targets indicated by genetic testing of the patient's tissue or peripheral blood, different drugs will be selected for maintenance, or a combination of previously effective and well-tolerated drugs will be chosen, or combination therapy will be selected with reference to previous tolerance. |
| treatment group（Regorafenib + Envafolimab） | Experimental | Drug: Regorafenib + EnvafolimabPatients in the treatment group will receive regorafenib combined with envafolimab. Regorafenib: 120 mg, orally, once daily, administered for 3 weeks followed by 1 week of rest. Envafolimab: 200 mg, subcutaneously injected, once every 2 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Aged ≥ 18 years, regardless of gender;
- Confirmed as gastrointestinal stromal tumor by histopathological examination;
- Having at least one measurable target lesion meeting the criteria of mRECIST v1.1 (non-lymph node lesions with a long axis ≥ 1.0 cm or a long axis ≥ the thickness of 2 slides); imaging assessment should be performed within 14 days before the first medication;
- Disease progression or intolerance after treatment with imatinib, sunitinib, regorafenib, or ripretinib;
- Primary or secondary KIT exon 17 mutation detected by genetic testing;
Key exclusion criteria (13 listed)
- A history of intolerance to regorafenib treatment, or previous receipt of immune checkpoint inhibitor therapy;
- Being in pregnancy or lactation;
- Those with an expected survival period of less than 3 months;
- Those who have undergone major surgery or suffered significant trauma within 4 weeks before the first blood collection during the screening period, or are expected to require major surgery during the study period;
- Patients with current active ulcers or gastrointestinal bleeding;
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 |
|---|---|---|
| physician-selected treatmentphysician-selected treatment | Drug | control group（physician-selected） |
| Regorafenib + EnvafolimabRegorafenib: 120mg, orally, qd, administered for 3 weeks followed by 1 week of rest. Envafolimab: 200mg, subcutaneously injected, q21d. | Drug | treatment group（Regorafenib + Envafolimab） |
Primary outcome
Progression Free Survival（PFS）
Time frame: Up to 2 years
Defined as the time from date of study treatment to disease progression radiological/clinical or death due to any cause, whichever occurs first.
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 30 Apr 2026.
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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.
Jian Li, MD study chair
Peking University Cancer Hospital & Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing physician-selected treatment and Regorafenib + Envafolimab in people with GIST - Gastrointestinal Stromal Tumor and KIT Gene Mutation, run by Jian Li at 1 site in China.
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 9 inclusion and 13 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 30 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 China. 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 phase mean?
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 Jian Li, MD (+86 010 88196561, oncogene@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival（PFS） (time frame: Up to 2 years). 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 30 Apr 2026; AzTrials last refreshed its copy on 7 Nov 2026.