This is an open-label, single-arm study of ATG-010 (selinexor) plus low-dose Dexamethasone (Sd) in patients with multiple myeloma previously treated with lenalidomide and bortezomib refractory to prior treatment with immunomodulatory agents and proteasome Inhibitors.

This is a single-arm, open-label, multicenter study of ATG-010 (Selinexor) plus low dose Dexamethasone dosed twice weekly each week in four-week cycles, in patients with triple-refractory MM. The population refractory for the primary efficacy analysis will contain only patients with triple-MM enrolled. PK analysis would be performed which would contain approximately 30% of the patients enrolled. Safety analyses will be performed on the overall population of patients who received at least one dose of study drug among triple-refractory patient populations. Patients will receive treatment until progressive disease (PD), death, toxicity that cannot be managed by standard care, or withdrawal, whichever occurs first.

Inclusion Criteria:

1. Written informed consent in accordance with federal, local, and institutional guidelines.

2. Age ≥ 18 years at the time of signing informed consent.

3. Patients must have previously received including proteasome inhibitors (PI) (i.e., lenalidomide) and immunomodulatory drugs (i.e., bortezomib) and were refractory to both drugs.

4. Any clinically significant non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #17) that patients experienced from treatments in previous clinical studies must have resolved to Grade ≤ 2 by Cycle 1 Day 1.

5. Adequate hepatic function within 21 days prior to Cycle 1 Day 1: total bilirubin < 2x upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3x ULN), AST < 2.5x ULN and ALT < 2.5x ULN.

6. Adequate renal function within 21 days prior to Cycle 1 Day 1: estimated creatinine clearance of ≥ 20 mL/min, calculated using the formula of cockroft and gault.

7. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

8. Measurable MM based on IMWG guidelines.

9. Adequate hematopoietic function within 21 days prior to Cycle 1 Day 1 (See Exclusion Criterion #20 for transfusion washout periods for RBCs and platelets):

   1. Hemoglobin level ≥ 8.5 g/dL
   2. ANC ≥ 1000/mm^3
   3. Platelet count ≥ 75,000/mm^3 (patients in whom < 50% of bone marrow nucleated cells are plasma cells) or ≥ 50,000/mm^3 (patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells. [Platelet transfusions < 1 week prior to Cycle 1 Day 1 are prohibited (see below).]

10. Female subjects of child-bearing potential must have both of the following:

    1. Agree to the use of two study physician-approved contraceptive methods simultaneously, or practice complete abstinence starting at the time of ICF signature, while on study medication, and 3 months following the last dose of study drug.
    2. Have negative serum pregnancy test result at screening.

Exclusion Criteria:

• The presence of any of the following will exclude a subject from enrollment:

  1. Active smoldering MM.

  2. Active plasma cell leukemia.

  3. Documented systemic amyloid light chain amyloidosis.

  4. Active central nervous system (CNS) MM.

  5. Pregnancy or breastfeeding.

  6. Chemotherapy ≤ 4 week, radiation and immunotherapy ≤ 4 weeks prior to Cycle 1 Day 1, and radio-immunotherapy 6 weeks prior to Cycle 1 Day 1.

  7. Active graft vs. host disease (after allogeneic stem cell transplantation) at Cycle 1 Day 1

  8. Life expectancy of < 4 months.

  9. Major surgery within four weeks prior to Cycle 1 Day 1.

  10. Active, unstable cardiovascular function:

      1. Symptomatic ischemia, or
      2. Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or
      3. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, or
      4. Myocardial infarction (MI) within 3 months prior to Cycle 1 Day 1.

  11. Prior exposure to a SINE compound, including ATG-010.