Elotuzumab, Selinexor, and Dexamethasone for Relapsed Refractory Multiple Myeloma

Inclusion Criteria: Patients must meet all of the following inclusion criteria to be eligible to enroll in thisstudy:

1. Age ≥ 18 years
2. Willing and able to provide written informed consent in accordance with federal,local, and institutional guidelines. The patient must provide informed consent priorto the first screening procedure
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of ≤ 2
4. Having measurable MM based on the modified International Myeloma Working Group (IMWG)guidelines, defined by at least one of the following: Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP), urinary M-protein excretion ≥ 200 mg/24hours by urine electrophoresis (UPEP), and free light chain (FLC) ≥ 100 mg/L, providedthat the FLC ratio is abnormal.
5. Patients with non-secretory multiple myeloma will be included if they have 25% or moreof plasmacytoma size progression or appearance of new plasmacytoma lesions.
6. Must have at least previously received ≥ 1 anti-MM regimens
7. More than 6 months have passed since an allogeneic transplant or 100 days since anautologous stem cell transplant, if patients had any
8. Adequate hepatic function within 28 days prior to C1D1:
9. Total bilirubin < 1.5 × upper limit of normal (ULN) (except patients withGilbert's syndrome who must have a total bilirubin of < 3 × ULN), and
10. Aspartate aminotransferase (AST) and alanine aminotransferase (3) normal to<2 ×ULN.
11. Calculated creatinine clearance (CrCl) >15 mL/min based on the Cockcroft and Gaultformula.
12. Adequate hematopoietic function within 7 days prior to C1D1: total white blood cell (WBC) count ≥1500/mm3, absolute neutrophil count ≥1000/mm3, hemoglobin ≥8.5 g/dL and platelet count ≥75,000/mm3
13. Patients receiving hematopoietic growth factor support, including erythropoietin,darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocytemacrophage-colony stimulating factor (GM-CSF), and platelet stimulators (eg,eltrombopag, romiplostim, or interleukin-11) must have at least a 2-week intervalbetween growth factor support and the Screening assessments, but they may receivegrowth factor support during the study.
14. 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.

11. Female patients of childbearing potential must have a negative serum pregnancy test atScreening. Female patients of childbearing potential and fertile male patients who aresexually active with a female of childbearing potential must use highly
12. Effective methods of contraception throughout the study and for 3 months following thelast dose of study treatment.

Exclusion Criteria: Patients meeting any of the following exclusion criteria are not eligible to enroll in thisstudy:

1. Has received selinexor or another XPO1 inhibitor previously.
2. Has any concurrent medical condition or disease (eg, uncontrolled active hypertension,uncontrolled active diabetes, active systemic infection, etc.) that is likely tointerfere with study procedures.
3. Uncontrolled active infection requiring parenteral antibiotics, antivirals, orantifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylacticantibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
4. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
5. Pregnant or breastfeeding females.
6. Life expectancy of <6 months
7. Major surgery within 6 weeks prior to C1D1.
8. 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.
9. Patients with untreated hepatitis C virus (HCV) are eligible if there is adocumentation of negative viral load per institutional standard.
10. Patients with history of human immunodeficiency virus (HIV) are eligible if they havecluster of differentiation 4 (CD4+ )T-cell counts ≥350 cells/µL, negative viral loadper institutional standard, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.
11. Any active gastrointestinal dysfunction interfering with the patient's ability toswallow tablets, or any active gastrointestinal dysfunction that could interfere withabsorption of study treatment.
12. Inability or unwillingness to take supportive medications such as anti-nausea andanti-anorexia agents as recommended by the National Cancer Comprehensive Network (NCCN) for antiemesis and anorexia/cachexia (palliative care).
13. Any active, serious psychiatric, medical, or other conditions/situations that, in theopinion of the Investigator, could interfere with treatment, compliance, or theability to give informed consent.
14. Contraindication to any of the required concomitant drugs or supportive treatments.
15. Patients unwilling or unable to comply with the protocol including providing 24-hoururine samples for urine protein electrophoresis at the required time points.