Phase Ib Study of SUnitinib Alternating With REgorafenib in Patients With Metastatic and/or Unresectable GIST

Inclusion Criteria: * At least 18 years of age at the time of study entry. * Histologically confirmed metastatic and/or unresectable GIST. Patients must demonstrate prior failure to at least imatinib, sunitinib and regorafenib (4th line and beyond). Any number of previous therapies for GIST is allowed. * Measurable disease per modified RECIST 1.1. A lesion in a previously irradiated area is ineligible to be considered as measurable disease unless there is objective evidence of progression of the lesion prior to study enrollment. * ECOG performance status 0 or 1 (see Appendix A). * Participants must have adequate organ and marrow function as outlined in the protocol. * Patients must be able to swallow oral medication. * Willingness to use effective means of birth control throughout the duration of clinical study and for at least 3 months after completion of study drug. * Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of study drug administration. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Use of any approved tyrosine kinase inhibitors or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is shorter, prior to receiving study drugs. * Patients with intolerance to sunitinib and/or regorafenib. * Participants who have had radiotherapy within 4 weeks prior to study entry. * Major surgery, or significant traumatic injury within 4 weeks prior to study entry. * Presence of symptomatic or uncontrolled brain or central nervous system metastases. * Known or suspected allergy to the investigational agent or any agent given in association with this trial. * Individuals with a history of a different malignancy, other than cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy OR other primary malignancy is neither currently clinically significant nor requiring active intervention. * Clinically significant cardiac arrhythmias and/or patients who require anti-arrhythmic therapy (excluding beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded. * History of clinically significant cardiac disease or congestive heart failure \> NYHA class 2 (See Appendix C). Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months. * Hypertension as defined by systolic blood pressure \>140 mmHg or diastolic blood pressure \> 90 mmH despite optimal medical management. * Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than 1 month before the start of study medication). * Patients with evidence or history of any bleeding diathesis, irrespective of severity. * Ongoing infection ≥ Grade 2. * Patients with any seizure disorder requiring medication. * Non-healing wound, ulcer, or bone fracture. * Persistent proteinuria Grade 2 or higher measured by urine protein:creatinine ratio on a urine sample or during 24-hour assessment. * HIV-positive individuals on combination antiretroviral therapy. * Patients with active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy. * Interstitial lung disease with ongoing signs and symptoms at the time of informed consent. * Uncontrolled intercurrent illness. * Pregnant or lactating females. * Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol. * Strong CYP3A4 inhibitors within 28 days or 5 drug half-lives, whichever is longer, before start of study drug.