A Study to Learn How Safe and How Well Linvoseltamab Works Compared to Standard Treatment in Adult Patients With Multiple Myeloma Who Are Not Eligible for Transplant

NCT06932562 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: EMN392024-519827-16-00
• Study Type: interventional
• Target: 1,000
• Locations: 16 countries
• Sites: 49

Brief Summary

This study is researching an experimental drug called linvoseltamab. The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplantation (transplant-ineligible). The main purpose of this study is to compare the effect and safety of linvoseltamab with the effect and safety of the standard treatment.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma (MM); Transplant ineligible; Newly diagnosed; Linvoseltamab; BCMA X CD3 bispecific antibody; CD38 antibody; Lenalidomide

Outcome Measures

Primary Outcomes (4)

• Minimal Residual Disease (MRD)

  Minimal Residual Disease (MRD) negative Complete Remission (CR) status at 10\^-5 per International Myeloma Working Group (IMWG) criteria

  up to 11 years

• MRD negative CR status by BICR

  MRD negative CR status at 10\^-5 as determined by the Blinded Independent Central Review (BICR)

  up to 11 years

• Progression Free Survival (PFS) per IMWG criteria

  defined as the time from the date of randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier, where disease progression is determined per IMWG criteria.

  up to 11 years

• PFS as determined by BICR

  defined as the time from the date of randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier, where disease progression is determined per by BICR.

  up to 11 years

Secondary Outcomes (25)

• Overall Survival (OS)

  up to 11 years

• Objective Response (OR) of Complete Response (CR)

  up to 11 years

• OR of Very Good Partial Response (VGPR)

  up to 11 years

• OR of Partial Response (PR)

  up to 11 years

• Sustained MRD

  up to 11 years

Study Arms (2)

Control arm DRd

ACTIVE COMPARATOR

Drug: Daratumumab; Drug: Lenalidomide; Drug: Dexamethasone

Experimental Arm DRd+ linvolsetamab

EXPERIMENTAL

Drug: Linvoseltamab; Drug: Daratumumab; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Dexamethasone DRUG

Administered per the protocol

Control arm DRd; Experimental Arm DRd+ linvolsetamab

Linvoseltamab DRUG

Administered per the protocol

Also known as: REGN5458

Experimental Arm DRd+ linvolsetamab

Daratumumab DRUG

Administered per the protocol

Control arm DRd; Experimental Arm DRd+ linvolsetamab

Lenalidomide DRUG

Administered per the protocol

Control arm DRd; Experimental Arm DRd+ linvolsetamab

Eligibility Criteria

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

You may qualify if:

• Participants must have confirmed diagnosis of symptomatic MM per IMWG criteria.
• Participants must not be considered a candidate for high-dose chemotherapy (HDT) and ASCT, as described in the protocol.
• Participants must have measurable disease as defined in the protocol.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Participants must have clinical laboratory values within a prespecified range.

You may not qualify if:

• International Myeloma Working Group Frailty Index of 2 with the exception of participants who have a score of 2 based on age alone.
• Participants who defer transplant due to personal preference.
• Participants with non-secretory MM, active plasma cell leukemia, known light-chain (AL) amyloidosis in the presence of a concurrent diagnosis of myeloma, any other form of amyloidosis, Waldenström macroglobulinemia, or known POEMS syndrome.
• Any prior therapy for monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or MM, with the exception of:
• focal radiation and/or
• a short course of corticosteroids as defined in the protocol.
• Participants who have received or are receiving any investigational agent or cell therapy with known or suspected activity against MM
• Participants who have known central nervous system (CNS) or meningeal involvement with MM or known or suspected progressive multifocal leukoencephalopathy (PML), a history of a neurocognitive condition or CNS movement disorder, OR a history of seizure, transient ischemic attack (TIA), stroke or seizure within 12 months prior to study C1D1.
• Participants who have uncontrolled intercurrent illness.
• Known contraindications to the use of daratumumab or lenalidomide per local prescribing information.
• History of allogeneic hematopoietic stem cell transplantation or solid organ transplant at any time.

Sponsors & Collaborators

• European Myeloma Network B.V.: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (59)

Flinders Medical Centre

Adelaide, Australia

RECRUITING

Box Hill Hospital

Box Hill, Australia

RECRUITING

Canberra Hospital

Canberra, Australia

RECRUITING

Barwon Health, University Hospital Geelong

Geelong, Australia

RECRUITING

Austin Hospital

Heidelberg, Australia

RECRUITING

Nepean Cancer Centre

Kingswood, Australia

RECRUITING

Northern Hospital

Melbourne, Australia

RECRUITING

Sunshine Coast Health

Sunshine Coast, Australia

RECRUITING

Ordensklinikum Linz

Linz, Austria

RECRUITING

Klinik Ottakring

Vienna, Austria

RECRUITING

University Hospital Centre Zagreb - Clinic for Internal Medicine

Zagreb, Croatia

RECRUITING

Fakultni Nemocnice Hradec Kralove

Hradec Králové, Czechia

RECRUITING

University Hospital Olomouc

Olomouc, Czechia

RECRUITING

Fakultni Nemocnice Ostrava

Ostrava, Czechia

RECRUITING

Fakultni Nemocnice Plzen

Pilsen, Czechia

RECRUITING

Aarhus Universitetshospital

Aarhus, Denmark

RECRUITING

North Estonia Medical Centre Foundation

Tallinn, Estonia

RECRUITING

Tartu University Hospital

Tartu, Estonia

RECRUITING

Helsinki University Hospital Comprehensive Cancer Center

Helsinki, Finland

RECRUITING

Kuopio University Hospital

Kuopio, Finland

RECRUITING

Universitaetsmedizin Greifswald

Greifswald, Germany

RECRUITING

Universitaetsklinikum Schleswig-Holstein -Campus Luebeck - Klinik fuer Haematologie und Onkologie

Lübeck, Germany

RECRUITING

University Hospital of Würzburg

Würzburg, Germany

RECRUITING

University Hospital of Alexandroupolis

Alexandroupoli, Greece

RECRUITING

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

Athens, Greece

RECRUITING

Evaggelismos Hospital

Athens, Greece

RECRUITING

Theagenion Cancer Hospital

Thessaloniki, Greece

RECRUITING

Cork University Hospital

Cork, Ireland

RECRUITING

Beaumont Hospital

Dublin, Ireland

RECRUITING

University Hospital Limerick - Department of Haematology

Limerick, Ireland

RECRUITING

AOU Ospedali Riuniti di Ancona

Ancona, Italy

RECRUITING

Azienda Ospedaliera Santa Croce e Carle - Ematologia

Cuneo, Italy

RECRUITING

A.O.U. Careggi

Florence, Italy

RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, Italy

RECRUITING

Ospedale di Legnano, ASST Ovest Milanese

Legnano, Italy

RECRUITING

Meldola-Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)

Meldola, Italy

RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

RECRUITING

Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda - Oncologia

Milan, Italy

RECRUITING

Azienda USL IRCCS Di Reggio Emilia

Reggio, Italy

RECRUITING

Ospedale "Infermi" di Rimini

Rimini, Italy

RECRUITING

I.R.C.C.S. Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

RECRUITING

Erasmus MC

Rotterdam, Netherlands

RECRUITING

Stavanger University Hospital

Stavanger, Norway

RECRUITING

St. Olavs hospital HF

Trondheim, Norway

RECRUITING

Vestfold Hospital Trust

Tønsberg, Norway

RECRUITING

CHUC

Coimbra, Portugal

RECRUITING

Hospital da Luz Lisboa

Lisbon, Portugal

RECRUITING

Institut Catala D'oncologia (Badalona)

Badalona, Spain

RECRUITING

Hospital Clinic De Barcelona - Myeloma and Amyloidosis Unit

Barcelona, Spain

RECRUITING

Hospital Quirón Salud Madrid

Madrid, Spain

RECRUITING

Hospital Universitario Marques De Valdecilla -Hematology and Hemotherapy Service

Santander, Spain

RECRUITING

Hospital Universitario la Fe, Valencia

Valencia, Spain

RECRUITING

Skåne University Hospital, Region Skåne

Lund, Sweden

RECRUITING

Universitaetsspital Basel - Zentrum fur Hamato-Onkologie

Basel, Switzerland

RECRUITING

Kantonsspital St. Gallen

Sankt Gallen, Switzerland

RECRUITING

Ankara University Faculty of Medicine, Department of Hematology

Ankara, Turkey (Türkiye)

RECRUITING

Liv Hospital Ankara

Ankara, Turkey (Türkiye)

RECRUITING

Ege Universitesi Tip Fakultesi - Hematology

Izmir, Turkey (Türkiye)

RECRUITING

Ege University Medicine Faculty, Izmir

Izmir, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Lenalidomide; 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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Roberto Mina

  A.O.U. Città della Salute e della Scienza di Torino

  PRINCIPAL INVESTIGATOR

• Claudia Stege

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Silvia Villa

CONTACT

+31 10 268 70 65; silvia.villa@emn.org

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: April 10, 2025
• First Posted: April 17, 2025
• Study Start: December 23, 2025
• Primary Completion (Estimated): December 1, 2036
• Study Completion (Estimated): December 1, 2036
• Last Updated: March 25, 2026

Record last verified: 2025-11

Locations

DK (1); NL (1); CH (2); TU (4); FI (2); CZ (4); AU (2); DE (3); ES (5); IT (11); NO (3); PT (2); CR (1); IE (3); SE (1); GR (4)