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

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.