Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)

This oncology study will be a phase 2 study for patients with advanced or metastatic GIST.
This study will determine overall response rate at 6 months for TMZ therapy in patients with
SDH-mutant/deficient GIST.

Treatment will continue for 6 months (with option to continue if benefiting treatment) or
until disease progression or unacceptable toxicity (whichever occurs first). All patients
will have regular evaluations for assessment of safety parameters. Temozolomide dose may be
held and/or modified for the management of adverse treatment effects according to
pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to
assess tumor resection.

An end of treatment visit for clinical evaluations and safety assessments will be performed
approximately 28 days (7 days) after the last dose of study drug. Patients discontinuing
study treatment will be followed every 3-6 months for disease recurrence and survival.

Inclusion Criteria:

1. Patient has pathologically confirmed SDH-mutant/deficient GIST.

2. Has recovered from the acute toxic effects of all prior chemotherapy, immunotherapy,
or radiotherapy.

3. Patient has an ECOG Performance Status of 0-2.

4. Patient has adequate hematologic, hepatic and renal function.

5. Female patient of childbearing potential has a negative serum or urine pregnancy
within 72 hours prior to receiving the first dose of study medication.

6. Female patient of childbearing potential agrees to use 2 methods of birth control or
be surgically sterile, or abstain from heterosexual activity for the course of the
study through 120 days after the last dose of study medication.

7. Male patient with a partner of childbearing potential agrees to use an adequate method
of contraception starting with the first dose of study therapy through 120 days after
the last dose of study therapy.

8. Has measurable or evaluable disease as per RECIST v1.1 (Appendix B).

9. Life expectancy of >12 weeks.

Exclusion Criteria:

1. Patients who have had major surgery within 4 weeks of initiation of study medication.

2. Patients who are receiving other concurrent anti-neoplastic therapy (e.g.,
chemotherapy, targeted therapy, immunotherapy, or radiotherapy) at the start of study
treatment.

3. Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events.

4. Evidence of severe or uncontrolled systemic diseases [e.g., unstable or uncompensated
respiratory, cardiac (including life threatening arrhythmias)].

5. Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy except alopecia
(if applicable) unless agreed that the patient can be entered after discussion with
the Medical Monitor.

6. Presence of cardiac impairment class III and IV definitions; OR history of myocardial
infarction/active ischemic heart disease within one year of study entry; OR
uncontrolled dysrhythmias; OR poorly controlled angina.

7. Pregnant or breast-feeding females.

8. Medical condition such as uncontrolled infection (including HIV), uncontrolled
diabetes mellitus or cardiac disease which, in the opinion of the treating physician,
would make this protocol unreasonably hazardous for the patient.

9. Any concurrent condition which in the investigator's opinion makes it undesirable for
the subject to participate in this trial or which would jeopardize compliance with the
protocol.

10. Patients who cannot swallow oral formulations of the agent