A Study of Selinexor (Seli) + Low-dose Dexamethasone (LDD) in Penta-refractory Multiple Myeloma (MM), Seli and Bortezomib + LDD in Triple-class Refractory MM, and Seli and Pomalidomide + LDD in Relapsed Refractory MM

A Study of Selinexor (Seli) + Low-dose Dexamethasone (LDD) in Penta-refractory Multiple Myeloma (MM), Seli and Bortezomib + LDD in Triple-class Refractory MM, and Seli and Pomalidomide + LDD in Relapsed Refractory MM

A Phase 2b, Open-label Study of Selinexor Plus Low-dose Dexamethasone (Sd) in Patients With Penta-refractory Multiple Myeloma (MM), Selinexor and Bortezomib Plus Low-dose Dexamethasone (SVd) in Patients With Triple-class Refractory MM, and Selinexor and Pomalidomide Plus Low-dose Dexamethasone (SPd) in Patients With Relapsed Refractory MM.

The purpose of this study is to assess the efficacy, antitumor activity, safety and tolerability of selinexor plus low-dose dexamethasone in participants with penta-refractory multiple myeloma or selinexor and bortezomib plus low-dose dexamethasone in participants with triple-class refractory multiple myeloma or selinexor and pomalidomide plus low-dose dexamethasone in participants with relapsed and/or refractory multiple myeloma.

Multiple Myeloma, Selinexor, Penta-refractory Multiple Myeloma, Triple-class Refractory Multiple Myeloma, KPT-330

Participants will receive fixed dose of 40 milligram (mg) of Selinexor oral tablet followed by 20 mg of low-dose Dexamethasone oral tablet twice weekly (BIW) on Days 1, 3, 8, 10, 15, 17, 22, and 24 of each 28-day cycle.

Participants will receive fixed dose of 100 mg of Selinexor oral tablet followed by 40 mg of low-dose Dexamethasone oral tablet once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle. (Dexamethasone may be given as 20 mg on days 1 and 2 of each week).

Participants will receive fixed dose of 80 mg of Selinexor oral tablet followed by 20 mg of low-dose Dexamethasone oral tablet BIW on Days 1, 3, 8, 10,15, 17, 22, and 24 of each 28-day cycle.

Participants will receive fixed dose of 100 mg of Selinexor oral tablet on Days 1, 8, 15, 22, and 29 followed by 1.3 milligram per square-meter (mg/m^2) of Bortezomib subcutaneous (SC) injection on Days 1, 8, 15, and 22 and followed by 40 mg of low-dose Dexamethasone oral tablet on Days 1, 8, 15, 22, and 29 of each 35-day cycle (Dexamethasone dose may be split to 20 mg on days 1 and 2).

Participants will receive fixed dose of 40 mg of Selinexor oral tablet on Days 1, 8, 15, and 22 of each 28-day cycle followed by Pomalidomide 4 mg PO on Days 1 through 21 of each 28-day cycle and followed by 40 mg of low-dose Dexamethasone oral tablet on Days 1, 8, 15, and 22 of each 28-day cycle. (Dexamethasone dose 20 mg QW for those of >75 years old at the Investigator's discretion, before QW dosing of Selinexor; it may be divided over 1 to 4 days at the Investigator's discretion).

Inclusion Criteria: Age greater than or equal to (≥)18 years at the time of signing informed consent. Written informed consent in accordance with federal, local, and institutional guidelines. Measurable MM based on IMWG guidelines as defined by at least one of the following: Serum M-protein ≥ 0.5 gram per deciliter (g/dL) by serum protein electrophoresis (SPEP) or, for Immunoglobulin (Ig) A myeloma, by quantitative IgA. Urinary M-protein excretion ≥ 200 mg/24 hours. Free light chain (FLC) ≥ 100 milligram per liter (mg/L), provided that the FLC ratio is abnormal. Only for arms Sd-40 BIW, Sd-100 QW and Sd-80 BIW: Participants must have relapsed or refractory multiple myeloma (RRMM) and have previously received at least 4 anti-MM prior therapies and have MM that is refractory to previous treatment with at least 2 proteasome inhibitors (PIs), at least 2 immunomodulatory agent (IMiDs), and 1 anti-cluster of differentiation (CD38) monoclonal antibody. Refractory is defined as lesser than or equal to (≤) 25 percent (%) response to therapy, or progression during therapy or progression within 60 days after completion of therapy. Only for arm SVd: Participants must have previously received 1 to 5 anti-MM prior therapies and have MM that is refractory to previous treatment with at least 1 PI, at least 1 IMiD, and 1 anti- CD38 monoclonal antibody. Only for arm SPd: relapsed or refractory pomalidomide naïve MM with: documented evidence of progressive disease (PD) after achieving at least SD for ≥1 cycle during a previous MM regimen (i.e., relapsed MM); ≤25% response (i.e., patients never achieved ≥MR) or PD during or within 60 days from the end of the most recent MM regimen (i.e., refractory MM); previously undergone ≥2 cycles of lenalidomide and a PI (in separate therapeutic regimens [not for maintenance] or in combination). Only for arm SPd: only patients that were prescribed with pomalidomide as per standard of care will be enrolled in this arm at the discretion of the Investigators. Only for arm SPd: adequate hematopoietic function within 28 days prior to C1D1: total white blood cell (WBC) count ≥1,500/mm³, ANC ≥1,000/mm³, hemoglobin (Hb) ≥8.0 g/dL, Platelet count ≥100,000/mm³ Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. Female participants of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female participants, effective methods of contraception must be used throughout the study and for 7 months for female and 4 months for male following the discontinuation of study treatment. Participants agrees to provide bone marrow aspirate to be used for genetic testing of participants agrees to provide bone marrow aspirate to be used for genetic testing of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Exclusion Criteria: Active plasma cell leukemia. Documented systemic amyloid light chain amyloidosis. Active central nervous system MM. Only for SVd arm: Greater than Grade 2 peripheral neuropathy or Grade ≥ 2 peripheral neuropathy with pain at baseline, regardless of whether or not the participant is currently receiving medication. Radiation, chemotherapy, immunotherapy, or any other anticancer therapy (including investigational therapies) ≤ 2 weeks prior to Cycle 1 Day 1 (C1D1). (Steroids are permitted up to 1 pulse of 40 mg per day for 4 days in the 2 weeks prior to C1D1). Active graft vs. host disease (after allogeneic stem cell transplantation) at C1D1. Ongoing clinically significant non-hematological toxicities from prior treatments that are Grade greater than (>) 2 at C1D1. Inadequate hepatic function defined as total bilirubin ≥ 2x upper limit of normal (ULN) (≥ 3x ULN for participants with Gilbert's syndrome), aspartate transaminase (AST) ≥ 2.5x ULN, and alanine transaminase (ALT) ≥ 2.5x ULN. Inadequate renal function defined as estimated creatinine clearance of lesser than (<) 20 milliliter per minute (mL/min), calculated using the formula of Cockroft and Gault. Inadequate hematopoietic function defined as the following: Absolute neutrophil count (ANC) < 1000/cubic millimeter (mm³) Platelet count < 75,000/mm³ Hemoglobin (Hb) level < 8.5 g/dL Life expectancy of < 4 months, based on the opinion of the Investigator. Major surgery within 4 weeks prior to C1D1. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose. Active gastrointestinal dysfunction interfering with the ability to swallow tablets, or any gastrointestinal dysfunction that could interfere with absorption of the study treatment. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus RNA or hepatitis B virus surface antigen. Receipt of red blood cells (RBC) transfusions within 2 weeks of C1D1. Receipt of platelet transfusion within 1 week of C1D1. Receipt of the following blood growth factors within 2 weeks prior to C1D1: Granulocyte colony stimulating factor, granulocyte-macrophage colony stimulating factor, erythropoietin, or megakaryocyte growth factor. Female participants who are pregnant or lactating. Known intolerance, hypersensitivity, or contraindication to glucocorticoid therapy at C1D1. Concurrent therapy with approved or investigational anticancer therapeutic including topical therapies. Prior exposure to a SINE compound, including selinexor. Serious, active psychiatric or active medical conditions which, in the opinion of the Investigator or the Sponsor, could interfere with the participation in the study. Contraindication to any of the required concomitant drugs or supportive treatments.