A Study of Combination of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Subject With Previously Treated Multiple Myeloma

Inclusion Criteria:

1. Relapsed or refractory MM with measurable disease per IMWG guidelines as defined byat least 1 of the following:

2. Serum M-protein ≥0.5 g/dL (≥5 g/L) by serum protein electrophoresis (SPEP) or,for immunoglobulin (Ig) A or D myeloma, by quantitative serum IgA or IgD levels ≥ 0.5 g/dL.

3. Urinary M-protein excretion ≥200 mg/24 hours

4. Serum free light chain (FLC) ≥100 mg/L, provided that the FLC ratio is abnormal (normal FLC ratio: 0.26 to 1.65)

5. Received at least 1 and no more than 4 prior anti-MM lines of therapy. Inductiontherapy followed by stem cell transplant and consolidation/maintenance therapy willbe considered as 1 line of therapy.

6. Prior therapy that includes ≥ consecutive cycles of lenalidomide and a proteasomeinhibitor given alone or in combination

7. Prior therapy with an anti-CD38 mAb as part of their immedicate last treatment priorto study entry (Before protocol version2.0, patient with any prior therapy with ananti-CD38 mAb were eligible for the study).

8. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

9. Resolution of any clinically significant non-hematological toxicities (if any) fromprevious treatments to Grade ≤1 by Cycle 1 Day 1 (C1D1). Patients with Grade 2non-hematological toxicities may be included.

10. Adequate hepatic function within 28 days prior to C1D1:

11. Total bilirubin <2 × upper limit of normal (ULN) (except patients withGilbert's syndrome who must have a total bilirubin of <3 × ULN)

12. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 × ULN

13. Adequate renal function within 28 days prior to C1D1 (estimated creatinine clearance [CrCl] of ≥15 mL/min (not requiring dialysis), calculated using the formula ofCockcroft and Gault or measured by 24-hour urine collection).

14. Adequate hematopoietic function within 7 days prior to C1D1 defined as absoluteneutrophil count ≥1.5 x 109/L , hemoglobin ≥8.5 g/dL, and platelet count ≥100 x 109/L (patients for whom <50% of bone marrow nucleated cells are plasma cells) or ≥75 x 109/L (patients for whom ≥50% of bone marrow nucleated cells are plasmacells).

15. Patients receiving hematopoietic growth factor support, includingerythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF),granulocyte macrophage-colony stimulating factor (GM-CSF), and plateletstimulators (e.g., eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments,but they may receive growth factor support during the study.

16. Patients must have:

• At least a 2-week interval from the last red blood cell (RBC) transfusionprior to the Screening hemoglobin assessment, and
• At least a 1-week interval from the last platelet transfusion prior to theScreening platelet assessment. However, patients may receive RBC and/or platelet transfusions as clinicallyindicated per institutional guidelines during the study.

10. Patients with active hepatitis B virus (HBV) are eligible if antiviral therapy forhepatitis B has been given for >8 weeks and viral load is <100 IU/mL. Patients withevidence of non-active HBV should be discussed with the Medical Monitor and shouldbe monitored or receive prophylaxis at the discretion of the Investigator and studysite institutional guidelines

11. Patients with a history of hepatitis C virus (HCV) are eligible if they havereceived adequate curative anti-HCV treatment and HCV viral load is below the limitof quantification.

12. Patients with a history of human immunodeficiency virus (HIV) are eligible if theyhave CD4+ T cell counts ≥350 cells/µL, negative viral load, and no history ofacquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in thelast year and should be on established antiretroviral therapy (ART) for at least 4weeks.

13. Female patients of childbearing potential must have a negative serum pregnancy testwithin 10 to 14 days and a second test within 24 hours prior to the first dose ofstudy treatment. Female patients of childbearing potential and fertile male patientswho are sexually active must use highly effective methods of contraceptionthroughout the study and for 3 months following the last dose of study treatment.

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

15. Written informed consent signed in accordance with federal, local, and institutionalguidelines.

16. Patients must be able and willing to take enteric-coated aspirin according toclinical practice, or if history of prior thrombotic disease, must be fullyanticoagulated with warfarin (international normalized ratio [INR] 2-3) or betreated with full-dose, low molecular weight heparin, as if to treat deep venousthrombosis (DVT)/pulmonary embolism (PE) at the Investigator's discretion. Forpatient on warfarin, INR should be repeated as clinically indicated. Use ofalternative anticoagulants, such as direct oral anticoagulants, may be consideredper Investigator discretion.

Exclusion Criteria:

1. Smoldering MM.

2. Plasma cell leukemia.

3. Documented active systemic amyloid light chain amyloidosis.

4. Any history of central nervous system MM.

5. Prior treatment with:

6. A selective inhibitor of nuclear export (SINE) compound, including selinexor

7. Pomalidomide and/or elotuzumab.

8. Any concurrent medical condition or disease that is likely to interfere with studyprocedures.

9. Uncontrolled active infection requiring parenteral antibiotics, antivirals, orantifungals within 1 week prior to C1D1. Patients on prophylactic antibiotics orwith a controlled infection within 1 week prior to C1D1 are acceptable.

10. Known intolerance, hypersensitivity, or contraindication to any of the studytreatments.

11. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy includinginvestigational therapies and high dose dexamethasone (i.e., 40 mg daily for 4 daysper week) ≤2 weeks prior to C1D1. Patients on long-term glucocorticoids duringScreening do not require a washout period but must be able to tolerate the specifieddexamethasone dose in this study.

12. Prior autologous stem cell transplantation <60 days or allogeneic stem celltransplantation <4 months prior to C1D1.

13. Major surgery within 4 weeks prior to C1D1.

14. Active graft versus host disease after allogeneic stem cell transplantation.

15. Pregnant or breastfeeding females.

16. In the opinion of the Investigator, patients who are below their ideal body weightand would be unduly impacted by changes in their weight.

17. Clinically significant cardiac disease, including:

18. Myocardial infarction within 6 months before C1D1, or unstable or uncontrolleddisease/condition related to or affecting cardiac function (e.g., unstableangina, congestive heart failure, New York Heart Association Class III-IV).

19. Uncontrolled cardiac arrhythmia (CTCAE v. 5.0 Grade 2 or higher) or clinicallysignificant electrocardiogram (ECG) abnormalities.

20. Screening 12-lead ECG showing a baseline QT interval as corrected byFridericia's formula (QTcF) >470 msec.

21. Any active gastrointestinal dysfunction interfering with the patient's ability toswallow tablets, or any active gastrointestinal dysfunction that could interferewith absorption of study treatment.

22. Any active, serious psychiatric, medical, or other conditions/situations that, inthe opinion of the Investigator, could interfere with treatment, compliance, or theability to give informed consent.

23. Contraindication to any of the required concomitant drugs or supportive treatments.

24. Patients unwilling or unable to comply with the protocol.