The Efficacy and Safety of Temozolomide in SDH-deficient GIST

Inclusion Criteria:

1. Age 20 years or older, at the time of acquisition of informed consent

2. Histologically confirmed GIST with CD117(+), DOG-1(+)

3. Wild type GIST without KIT or PDGFRα gene mutations determined by Sanger sequencingand panel sequencing

4. Eastern Cooperative Oncology Group (ECOG) performance status 0 ~ 2

5. Resolution of all adverse events with prior treatments to grade 0 or 1 by NCI-CTCAEversion 5.0

6. At least one measurable lesion by RECIST version 1.1.

7. Adequate bone marrow, hepatic, renal, and other organ functions, before adjuvantimatinib treatment

• Neutrophil >1,500/mm3

• Platelet > 100,000/mm3

• Hemoglobin >8.0 g/dL

• Total bilirubin < 1.5 x upper limit of normal (ULN)

• AST/ALT < 2.5 x ULN

• Creatinine <1.5 x ULN

8. Life expectancy ≥12 weeks

9. Disease progression or discontinuation of treatment due to intolerable toxicity atleast with palliative 1st line imatinib .

10. Washout period of previous TKIs or chemotherapy for more than 4 times the half life ((Imitinib and regorafenib need 1 week and sunitinib need 2 weeks.)

11. Provision of a signed written informed consent

Exclusion Criteria:

1. Confirmed GIST with KIT or PDGFRα gene mutations determined by Sanger sequencing andpanel sequencing

2. Women of child-bearing potential who are pregnant or breast feeding

3. Women or men who are not willing to use effective contraception entering the studyperiod or until at least 6 months after the last study drug administration

4. If any of the following applies within ≤ 6 months prior to starting study enrollment : Myocardial Infarction, severe instable angina, coronary/peripheral bypass, NYHAclass III or IV congestive heart failure, stroke or transient ischemic attack,treatment required severe arrhythmia

5. Uncontrolled infection

6. Acute and chronic liver disease and all chronic liver impairment.(But Patients withstable chronic hepatitis B are eligible

7. Acute, or chronic medical or psychiatric condition or laboratory abnormality such asactive uncontrolled infection that difficult to study participation in the judgmentof the investigator

8. Known diagnosis of HIV infection (HIV testing is not mandatory).

9. History of another primary malignancy that is currently clinically significant orcurrently requires active intervention.

10. Alcohol or substance abuse disorder

11. The patients with NTRK fusion