Regorafenib plus envafolimab versus physician's choice for metastatic GIST with KIT exon 17 mutation

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

This study will test whether combining regorafenib with the immune drug envafolimab helps people with metastatic GIST who have KIT exon 17 mutations and have stopped responding to standard treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking University Cancer Hospital & Institute (other)
• Drugs / interventions: imatinib, sunitinib, ripretinib, envafolimab, immunotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07559864 on ClinicalTrials.gov

What this trial studies

This is a multicenter, prospective phase II randomized trial enrolling about 100 patients with metastatic GIST harboring KIT exon 17 mutations who progressed after standard therapies. Participants are randomized 1:1 to receive regorafenib plus envafolimab (regorafenib 120 mg orally daily, 3 weeks on/1 week off; envafolimab 200 mg subcutaneously every 2 weeks) or physician-selected targeted therapy or combinations. Treatment continues until disease progression, unacceptable toxicity, or withdrawal, with imaging assessments at baseline and every two months. The study will measure efficacy and safety and explore how features of the tumor immune microenvironment relate to response.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed metastatic GIST, a primary or secondary KIT exon 17 mutation, at least one measurable lesion, and prior progression or intolerance to imatinib, sunitinib, regorafenib, or ripretinib are eligible.

Not a fit: Patients without KIT exon 17 mutations, those still responding to approved therapies, or those with inadequate organ or bone marrow function are unlikely to benefit from this trial.

Why it matters

Potential benefit: If effective, the combination could improve tumor control and extend progression-free survival for patients with KIT exon 17–mutant metastatic GIST who have exhausted approved options.

How similar studies have performed: Preclinical data and early clinical signals suggest TKIs can modulate the immune microenvironment and may synergize with checkpoint inhibitors, but strong, consistent success in KIT exon 17–mutant GIST has not yet been established.

Eligibility criteria

Inclusion Criteria:

* 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;
* Provide 15 paraffin-embedded tissue sections before enrollment for immune microenvironment detection;
* ECOG PS score of 0-2;
* Signed informed consent form.

Exclusion Criteria:

* 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;
* 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.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Cancer Hospital — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Jian Li, MD

Conditions: GIST - Gastrointestinal Stromal Tumor, KIT Gene Mutation, Gastrointestinal Stromal Tumor, Treatment, kit gene