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

NCT05028348 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: EMN29
• Study Type: interventional
• Target: 117
• Locations: 4 countries
• Sites: 20

Brief Summary

This phase 3 randomized, open-label multicenter trial will compare the efficacy, safety and the impact on health-related quality of life (HR-QoL) of SPd versus EloPd in pomalidomide-naïve patients with MM who have received 1 to 4 prior anti-MM regimens and been treated with an immunomodulatory imide drug (IMiD), proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody (mAb).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  from date of randomization until the date of first confirmed progressive disease (PD), per IMWG response criteria, or death due to any cause, whichever occurs first.

  from randomization to the date of disease progression or death (approximately up to 5 years)

Secondary Outcomes (9)

• Overall Response Rate (ORR)

  from screening until end of treatment/progressive disease (approximately up to 2 years)

• Overall survival (OS)

  From randomization until death from any cause (up to 3 years after end of treatment)

• Duration of response

  screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment, and every 3 months up to 3 years

• Time to response

  screening, Day 1 of each treatment cycle (each cycle is 28 days), at end of treatment, and every 3 months up to 3 years

• Progression-free survival on the next line of therapy (PFS2)

  the time from randomization to progression on the next line of treatment or death, whichever comes first., assessed up to approx. 5 years

Study Arms (2)

Selinexor, pomalidomide and dexamethasone (SPd)

EXPERIMENTAL

Selinexor will be given as an oral dose: 40 mg (2 20 mg tablets) once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle. * Pomalidomide will be given as an oral 4 mg dose QD on Days 1 to 21 of each 28-day cycle. * Patients ≤75 years: o Dexamethasone will be given as an oral 40 mg dose QW on Days 1, 8, 15, and 22 of each 28-day cycle. Dose may be divided over 2 days at the Investigator's discretion. * Patients \> 75 years: * Dexamethasone will be given as an oral 20 mg dose QW on Days 1, 8, 15, and 22 of each 28-day cycle. Dose may be divided over 2 days at the Investigator's discretion.

Drug: Selinexor; Drug: Pomalidomide; Drug: Dexamethasone Oral

Elotuzumab, Pomalidomide and Dexamethasone (EloPd)

ACTIVE COMPARATOR

Elotuzumab will be given IV 10 mg/kg on Days 1, 8, 15, and 22 of cycle 1 and 2 then 20 mg/kg on Day 1 of cycles ≥3 of each 28-day cycle. * Pomalidomide will be given as an oral 4 mg dose once a day (QD) on Days 1 to 21 of each 28-day cycle. * Patients ≤75 years: * Dexamethasone 28 mg PO + 8 mg IV on days of elotuzumab dosing * Dexamethasone 40 mg PO on non-elotuzumab days (e.g., days 8, 15, and 22 of cycle 3 and beyond). Dose may be divided over 2 days at the Investigator's discretion. * Patients \>75 years: * Dexamethasone 8 mg PO + 8 mg IV on days of elotuzumab dosing * Dexamethasone 20 mg PO on non-elotuzumab dosing weeks (e.g., days 8, 15, and 22 of cycle 3 and beyond). Dose may be divided over 2 days at the Investigator's discretion.

Drug: Elotuzumab; Drug: Pomalidomide; Drug: Dexamethasone Oral

Interventions

Selinexor DRUG

Selinexor will be given as an oral dose 40 mg (2 20 mg tablets) QW on Days 1, 8, 15, and 22 of each 28-day cycle.

Also known as: KPT-330

Selinexor, pomalidomide and dexamethasone (SPd)

Elotuzumab DRUG

Elotuzumab will be given IV 10 mg/kg on Days 1, 8, 15, and 22 of cycle 1 and 2 then 20 mg/kg on Day 1 of cycles ≥3 of each 28-day cycle.

Elotuzumab, Pomalidomide and Dexamethasone (EloPd)

Pomalidomide DRUG

Pomalidomide will be given as an oral 4 mg dose QD on Days 1 to 21 of each 28-day cycle.

Elotuzumab, Pomalidomide and Dexamethasone (EloPd); Selinexor, pomalidomide and dexamethasone (SPd)

Dexamethasone Oral DRUG

Dexamethasone will be given as an oral 40 mg dose QW on Days 1, 8, 15, and 22 of each 28-day cycle. Preferred dosing of dexamethasone is 40 mg QW for patients who are ≤75 years of age (20 mg QW for \>75-year-old patients at the Investigator's discretion) before QW dosing of selinexor, however, it may be divided over 2 days at the Investigator's discretion.

Elotuzumab, Pomalidomide and Dexamethasone (EloPd); Selinexor, pomalidomide and dexamethasone (SPd)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed or refractory MM with measurable disease per IMWG guidelines as defined by at least 1 of the following:
• 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.
• Urinary M-protein excretion ≥200 mg/24 hours
• Serum free light chain (FLC) ≥100 mg/L, provided that the FLC ratio is abnormal (normal FLC ratio: 0.26 to 1.65)
• 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.
• Prior therapy that includes ≥ consecutive cycles of lenalidomide and a proteasome inhibitor given alone or in combination
• Prior therapy with an anti-CD38 mAb as part of their immedicate last treatment prior to study entry (Before protocol version2.0, patient with any prior therapy with an anti-CD38 mAb were eligible for the study).
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to Grade ≤1 by Cycle 1 Day 1 (C1D1). Patients with Grade 2 non-hematological toxicities may be included.
• Adequate hepatic function within 28 days prior to C1D1:
• Total bilirubin \<2 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \<3 × ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5 × ULN
• 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).
• Adequate hematopoietic function within 7 days prior to C1D1 defined as absolute neutrophil 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 plasma cells).
• 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., 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.

You may not qualify if:

• Smoldering MM.
• Plasma cell leukemia.
• Documented active systemic amyloid light chain amyloidosis.
• Any history of central nervous system MM.
• Prior treatment with:
• A selective inhibitor of nuclear export (SINE) compound, including selinexor
• Pomalidomide and/or elotuzumab.
• Any concurrent medical condition or disease that is likely to interfere with study procedures.
• 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.
• Known intolerance, hypersensitivity, or contraindication to any of the study treatments.
• 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.
• Prior autologous stem cell transplantation \<60 days or allogeneic stem cell transplantation \<4 months prior to C1D1.
• Major surgery within 4 weeks prior to C1D1.
• Active graft versus host disease after allogeneic stem cell transplantation.
• Pregnant or breastfeeding females.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: collaborator
• European Myeloma Network B.V.: lead

Study Sites (20)

CHRU Hôtel Dieu

Nantes, France

Location

CHU Hôpital Saint Antoine

Paris, France

Location

La Pitié

Paris, France

Location

Klinikum Chemnitz

Chemnitz, Germany

Location

Marien Hospital Dusseldorf

Düsseldorf, Germany

Location

University Medicine Greifswald, Medical Clinic and Polyclinic for Internal Medicine

Greifswald, Germany

Location

Universitätsklinikum Hamburg - Eppendorf

Hamburg, Germany

Location

Alexandra General Hospital -Department of Clinical Therapeutics N.K. Univ. of Athens

Athens, Greece

Location

Hospital Clinic I Provincial de Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Institut Catala D Oncolocia Hospitalet - Hospital Duran i Reynals

Barcelona, Spain

Location

Hospital de Cabueñes

Gijón, Spain

Location

Institut Català D'Oncologia - Hospital Dr. Josep Trueta

Girona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

H. General Universitario Morales Meseguer

Murcia, Spain

Location

Clínica Universidad de Navarra (CUN)

Pamplona, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

H. Universitario Marqués de Valdecilla

Santander, Spain

Location

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, Spain

Location

H.U. La Fe

Valencia, Spain

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor; elotuzumab; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: August 31, 2021
• Study Start: April 19, 2022
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2029
• Last Updated: December 4, 2025

Record last verified: 2025-09

Locations

ES (12); FR (3); GR (1); DE (4)