A Study of Regorafenib Combined With Envafolimab for Metastatic Gastrointestinal Stromal Tumors With Kit Gene Exon 17 Mutation That Failed Standard Treatment

Inclusion Criteria:

* Age ≥ 18 years, no gender restriction;
* Pathologically confirmed gastrointestinal stromal tumor (GIST);
* At least one measurable target lesion according to mRECIST v1.1 criteria (non-lymph node lesion with a long axis ≥ 1.0 cm or long axis ≥ 2 slide thicknesses); imaging assessment within 14 days before the first dose;
* Progression or intolerance after treatment with imatinib, sunitinib, regorafenib, or ripretinib;
* Genetic testing includes primary or secondary KIT exon 17 mutation;
* Adequate organ and bone marrow function, defined as follows:

Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; platelet count (PLT) ≥ 75 × 10\^9/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 testing; Liver and kidney function: For patients without liver metastasis, total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. For patients with liver metastasis: TBIL ≤ 1.5 × ULN; ALT and AST ≤ 5 × ULN. Kidney function: serum creatinine (Scr) ≤ 1.5 × ULN; Adequate coagulation function, defined as international normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 × ULN; if the patient is on anticoagulant therapy, PT should be within the intended range of the anticoagulant;

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

Exclusion Criteria:

* Unable to tolerate previous regorafenib treatment or previously received immune checkpoint inhibitors;
* Pregnant or breastfeeding;
* Expected survival less than 3 months;
* Underwent major surgery or experienced significant trauma within 4 weeks before the first blood draw during the screening period, or expected to need major surgery during the study;
* Currently have active ulcers or gastrointestinal bleeding;
* History of interstitial lung disease or non-infectious pneumonia; history of active tuberculosis;
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
* Clinically diagnosed autoimmune disease; HIV or HCV positive; HBV-DNA exceeding laboratory normal range; acute CMV infection;
* Patients with central nervous system metastasis;
* Patients with other malignancies within the past five years;
* Immunosuppressed subjects, including those with known immunodeficiency; currently using systemic steroids (except for recent or current use of inhaled steroids);
* Uncontrolled hypertension: Despite aggressive antihypertensive therapy, sequential measurements show systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥100 mmHg on three consecutive occasions;
* Subjects deemed by the investigator to be unable or unwilling to comply with the study protocol requirements.