A PHASE 3 RANDOMIZED, OPEN-LABEL TRIAL OF SELINEXOR, POMALIDOMIDE, AND DEXAMETHASONE (SPd) VERSUS ELOTUZUMAB, POMALIDOMIDE, AND DEXAMETHASONE (EloPd) IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM)

There is no difference in the patient population enrolled in Part 1 or Part 2
of the study. 1. Relapsed or refractory MM per IMWG criteria with measurable
disease as defined by at least 1 of the following: a. 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. b. Urinary
M-protein excretion >=200 mg/24 hours. c. Serum free light chain (FLC) >=100
mg/L, provided that the FLC ratio is abnormal (normal FLC ratio: 0.26 to 1.65).
2. Received at least 1 and no more than 4 prior anti-MM lines of therapy.
Induction therapy followed by stem cell transplant and
consolidation/maintenance therapy will be considered as 1 line of therapy. 3.
Prior therapy that includes >=2 consecutive cycles of lenalidomide and a
proteasome inhibitor given alone or in combination.
4. Prior therapy with an anti-CD38 mAb as part of their immediate last line of
therapy prior to study entry (Before protocol version 2.0 patients with any
prior therapy with an anti-CD38 mAb were eligible for the study.) 5. Eastern
Cooperative Oncology Group (ECOG) performance status of <=2. 6. Resolution of
any clinically significant non-hematological toxicities (if any) from previous
treatments to Grade <=1 by Cycle 1 Day 1 (C1D1). Patients with clinically
significant Grade 2 neuropathy from previous treatments may be included. 7.
Adequate hepatic function within 28 days prior to C1D1: a. Total bilirubin <2 ×
upper limit of normal (ULN) (except patients with Gilbert's syndrome who must
have a total bilirubin of <3 × ULN) b. Aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) <2.5 × ULN 8. Adequate renal function within 28
days prior to C1D1 (estimated creatinine clearance [CrCl] of >=15 mL/min (not
requiring dialysis), calculated using the formula of Cockcroft and Gault or
measured by 24-hour urine collection). 9. Adequate hematopoietic function
within 7 days prior to C1D1 defined as absolute neutrophil count >=1.5 x 10^9/L,
hemoglobin >=8.5 g/dL, and platelet count >=100 x 10^9/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 plasma cells) a. Patients
receiving hematopoietic growth factor support, including erythropoietin,
darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte
macrophage colony stimulating factor (GM-CSF), and platelet stimulators (e.g.,
romiplostim, or eltrombopag) must have a 2-week interval between growth factor
support and the Screening assessments. b. Patients must have: - At least a
2-week interval from the last red blood cell (RBC) transfusion prior to the
Screening hemoglobin assessment, and - At least a 1-week interval from the last
platelet transfusion prior to the Screening platelet assessment. However,
patients may receive RBC and/or platelet transfusions as clinically indicated
per institutional guidelines during the study. 10. Patients with active
hepatitis B virus (HBV) are eligible if antiviral therapy for hepatitis B has
been given for >8 weeks and viral load is <100 IU/mL. Patients with evidence of
non-active HBV should be discussed with the Medical Monitor and should be
monitored or receive prophylaxis at the discretion of the Investigator and
study site institutional guidelines 11. Patients with a history of hepatitis C
virus (HCV) are eligible if they have received adequate curative anti-HCV
treatment and HCV viral load is below the limit of quantification. 12. Patients
with a history of human immunodeficiency virus (HIV) are eligible if they have
CD4+ T cell counts >=350 ells/µcL, negative viral load, and no history of
acquired immunodeficiency syndrome (AIDS)- defining opportunistic infections in
the last year and should be on established antiretroviral therapy (ART) for at
least 4 weeks.
13. Global (excluding Germany): Female patients of childbearing
potential must have a negative serum pregnancy test within 10 to 14
days and a second negative serum test within 24 hours prior to the first
dose of study treatment. Female patients of childbearing potential ho are
sexually active must agree to use a barrier method in addition to highly
effective methods of contraception throughout the study and for 90 days
following the last dose of study treatment.
Germany only: Premenopausal female patients of childbearing potential
must have a negative serum pregnancy test within 10 to 14 days and a
second negative serum test within 24 hours prior to the first dose of
study treatment. Premenopausal female patients of childbearing
potential who are sexually active must agree to use a barrier method in
addition to highly effective methods of contraception throughout the
study and for 90 days following the last dose of study treatment.
Please refer to protocol for inclusion criteria #14 to 17.

There is no difference in the patient population enrolled in Part 1 or Part 2
of the study. This trial will enroll patients who meet all of the inclusion
criteria and none of the exclusion criteria. 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: a. a selective inhibitor of nuclear export (SINE) compound, including
selinexor. b. pomalidomide or elotuzumab. 6. Any concurrent medical condition
or disease that is likely to interfere with study procedures. 7. Uncontrolled
active infection requiring parenteral antibiotics, antivirals, or antifungals
within 1 week prior to C1D1. Patients on prophylactic antibiotics or with a
controlled infection within 1 week prior to C1D1 are acceptable. 8. Known
intolerance, hypersensitivity, or contraindication to any of the study
treatments. 9. Radiation, chemotherapy, or immunotherapy or any other
anticancer therapy including investigational therapies and high dose
dexamethasone (i.e., 40 mg daily for 4 days per week) <=2 weeks prior to C1D1.
Patients on long-term glucocorticoids during Screening do not require a washout
period, but must be able to tolerate the specified dexamethasone dose in this
study. 10. Prior autologous stem cell transplantation <100 days or allogeneic
stem cell transplantation <4 months prior to C1D1. 11. Major surgery within 4
weeks prior to C1D1. 12. Active graft versus host disease after allogeneic stem
cell transplantation. 13. Pregnant or breastfeeding females. 14. In the opinion
of the Investigator, patients who are below their ideal body weight and would
be unduly impacted by changes in their weight. 15. Clinically significant
cardiac disease, including: a. Myocardial infarction within 6 months before
C1D1, or unstable or uncontrolled disease/condition related to or affecting
cardiac function (e.g., unstable angina, congestive heart failure, New York
Heart Association Class III-IV). b. Uncontrolled cardiac arrhythmia (CTCAE v.
5.0 Grade 2 or higher) or clinically significant electrocardiogram (ECG)
abnormalities. c. Screening 12-lead ECG showing a baseline QT interval as
corrected by Fridericia's formula (QTcF [APPENDIX 4]) >470 msec. 16. Any active
gastrointestinal dysfunction interfering with the patient's ability to swallow
tablets, or any active gastrointestinal dysfunction that could interfere with
absorption of study treatment. 17. Any active, serious psychiatric, medical, or
other conditions/situations that, in the opinion of the Investigator, could
interfere with treatment, compliance, or the ability to give informed consent.
18. Contraindication to or inability to tolerate any of the required
concomitant drugs such as dual antiemetics (Section 10.1.1 ), or supportive
treatments. 19. Patients unwilling or unable to comply with the protocol.