Gastrointestinal Stromal Tumor Clinical Trials

• 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

∙ 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