Inclusion Criteria:

          1. Age ≥18 years at the time of study entry.

          2. Histologically confirmed metastatic and/or unresectable GIST. Patients must
             demonstrate prior failure to at least imatinib. Any number of previous therapies for
             GIST is allowed.

          3. Failure of imatinib is defined as disease progression after ≥ 6 months of treatment
             with imatinib for advanced/metastatic disease. Exception to this rule is GIST patients
             with documented KIT or PDGFRA mutations.

          4. Measurable disease per modified RECIST 1.1.

          5. ECOG performance status 0 to 2.

          6. Adequate hematopoietic function (within 7 days prior to enrollment):

               1. Hemoglobin ≥ 9.0 g/dL (90 g/L).

               2. Absolute neutrophil count ≥ 1000/mm3.

               3. Platelets ≥ 100,000 /mm3. Patients must have at least a 2-week interval from the
                  last red blood cell (RBC) transfusion and/or growth factor support prior to the
                  Screening hemoglobin and neutrophil assessment. However, patients may receive
                  RBC, growth factor support, and/or platelet transfusions as clinically indicated
                  per institutional guidelines during the study.

          7. Adequate organ function (within 7 days prior to enrollment):

               1. Alanine aminotransferanse (ALT) and aspartate aminotransferanse (AST)

                  ≤2.5 x upper limit of normal (ULN), or ≤ 5.0 x ULN if liver metastases are
                  present.

               2. Alkaline phosphatase (ALP) limit < 2.5 x ULN or ≤ 5.0 x ULN if liver metastases
                  are present.

               3. Total serum bilirubin ≤ 2 x ULN. Patients with Gilbert's syndrome must have a
                  total bilirubin of < 3 × ULN.

               4. Adequate renal function: estimated creatinine clearance of ≥ 30 mL/min,
                  calculated using the formula of Cockroft and Gault

          8. Patients must be able to swallow oral medication and no malabsorption condition.

          9. 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.

         10. Women of childbearing potential must have a negative pregnancy test performed within 7
             days of the start of study drug administration.

         11. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Cohort A: Intolerance to first-line treatment imatinib 400mg daily.

          2. Use of any approved tyrosine kinase inhibitors or investigational agents within 1 week
             or 5 half-lives of the agent, whichever is shorter, prior to receiving study drugs.

          3. Participants who have had radiotherapy within 4 weeks prior to study entry.

          4. Major surgery or significant traumatic injury within 4 weeks prior to study entry.

          5. Presence of symptomatic or uncontrolled brain or central nervous system metastases.

          6. Known or suspected allergy or hypersensitivity to the selinexor, imatinib or any of
             its components.

          7. Patient has a history of another primary malignancy that has been diagnosed or
             required therapy within 1 year prior to the first dose of study drug (The following
             are exempt from the 1-year limit: completely resected basal cell and squamous cell
             skin cancer, curatively treated localized prostate cancer, and completely resected
             carcinoma in situ of any site.)

          8. Unstable cardiovascular function: • Symptomatic ischemia, or • Uncontrolled clinically
             significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic
             agents are excluded; 1st degree atrioventricular (AV) block or asymptomatic left
             anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded),
             or • Congestive heart failure (CHF) NYHA Class ≥ 3, or • Myocardial infarction (MI)
             within 3 months. • Left ventricular ejection fraction < 40 %. • Hypertension > 140 mm
             Hg systolic or > 90 mm Hg diastolic with or without antihypertensive therapy.

          9. Ongoing infection > Grade 2.

         10. Patients with any seizure disorder requiring medication.

         11. HIV-positive individuals on combination antiretroviral.

         12. Patients with active hepatitis B or C, or chronic hepatitis B or C requiring treatment
             with antiviral therapy.

         13. Serious psychiatric or medical conditions that could interfere with treatment.

         14. Pregnant or lactating females.

         15. Strong CYP3A4 inhibitors (e.g. clarithromycin, indinavir, itraconazole, ketoconazole ,
             nefazodone , nelfinavir , posaconazole, ritonavir, saquinavir, telithromycin,
             voriconazole) or strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, phenytoin,
             rifampin, St. John's Wort) within 28 days or 5 drug half-lives (if drug half-life in
             patients is known), whichever is longer, before start of study treatment.