A Trial to Learn How Well Linvoseltamab Works Compared to the Combination of Elotuzumab, Pomalidomide and Dexamethasone for Adult Participants With Relapsed/Refractory Multiple Myeloma (LINKER-MM3)

An Open-label, Randomized, Phase 3 Study of Linvoseltamab (REGN5458; Anti- BCMA x Anti-CD3 Bispecific Antibody) Versus the Combination of Elotuzumab, Pomalidomide, and Dexamethasone (EPd), in Patients With Relapsed/Refractory Multiple Myeloma (LINKER-MM3)

This study is researching an experimental drug called linvoseltamab, also called REGN5458.

Linvoseltamab has previously been studied by itself (without other cancer drugs) in participants who had advanced multiple myeloma that returned and needed to be treated again after many other therapies had failed. These participants were no longer benefiting from standard medications and had no good treatment options. In that study, some participants who were treated with linvoseltamab had improvement of their myeloma (shrinkage of their tumors), including some participants who had complete responses (that is, the treatment got rid of all evidence of myeloma in their bodies).

This study is focused on participants who have multiple myeloma that has returned or needs to be treated again after one to four prior treatments and have standard cancer treatment options available to them. The aim of this study is to see how safe and effective linvoseltamab is compared to a combination of three cancer drugs: elotuzumab, pomalidomide and dexamethasone, (called EPd) in participants who have returned after having received prior treatment that included lenalidomide, a proteosome inhibitor, and (for participants in some countries) a cluster of differentiation 38 (CD38) antibody. Half of the participants in this study will get linvoseltamab, and the other half will get EPd.

This study is looking at several other research questions, including:

• How long participants benefit from receiving linvoseltamab compared with EPd
• How many participants treated with linvoseltamab or EPd have improvement of their multiple myeloma and by how much
• What side effects happen from taking linvoseltamab compared to EPd
• How long participants live while receiving treatment or after treatment with linvoseltamab compared to EPd
• If there is any improvement in pain after treatment with linvoseltamab compared to EPd

Study Overview

• Status: Recruiting
• Conditions: Relapsed Refractory Multiple Myeloma (RRMM)
• Intervention / Treatment: Drug: Elotuzumab; Drug: Dexamethasone; Drug: Linvoseltamab; Drug: Pomalidomide

• Study Type: Interventional
• Enrollment (Estimated): 410
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Active, not recruiting
      • Royal Prince Alfred Hospital
    • St Leonards, New South Wales, Australia, 2065
      • Active, not recruiting
      • Royal North Shore Hospital
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Active, not recruiting
      • Icon Cancer Centre - Wesley
    • Herston, Queensland, Australia, 4029
      • Active, not recruiting
      • Royal Brisbane and Women's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Active, not recruiting
      • Royal Adelaide Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Active, not recruiting
      • Royal Hobart Hospital
    • Launceston, Tasmania, Australia, 7250
      • Active, not recruiting
      • Launceston General Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Active, not recruiting
      • St Vincent's Hospital
    • Geelong, Victoria, Australia, 3220
      • Active, not recruiting
      • University Hospital Geelong
    • Heidelberg, Victoria, Australia, 3084
      • Active, not recruiting
      • Austin Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Active, not recruiting
      • One Clinical Research at Hollywood Private Hospital
• Belgium
  • Antwerp, Belgium, 2060
    • Active, not recruiting
    • Ziekenhuis Netwerk Antwerpen Stuivenberg
  • Brussels, Belgium, 1200
    • Withdrawn
    • Cliniques universitaires Saint-Luc
  • Namur
    • Yvoir, Namur, Belgium, 5530
      • Completed
      • Clinique Universitaire de Mont Godinne
  • West-Vlaanderen
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • Active, not recruiting
      • AZ Delta Algemeen Ziekenhuis Delta
• Brazil
  • Rio de Janeiro, Brazil, 22793-080
    • Active, not recruiting
    • Instituto Americas de Ensino e Pesquisa
  • São Paulo, Brazil, 01401-002
    • Active, not recruiting
    • Instituto Dor de Pesquisa E Ensino
  • São Paulo, Brazil, 04537-080
    • Active, not recruiting
    • Clinica Medica Sao Germano
  • São Paulo, Brazil, 01321000
    • Active, not recruiting
    • A Beneficencia Portuguesa de Sao Paulo, Oncology House
  • São Paulo, Brazil, 01509-010
    • Active, not recruiting
    • AC Camargo Cancer Center
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253-190
      • Active, not recruiting
      • IDOR - Sao Rafael Salvador Bahia
  • Paraná
    • Curitiba, Paraná, Brazil, 81520-060
      • Active, not recruiting
      • Hospital Erasto Gaertner
  • Rio Grande do Sul
    • Bento Gonçalves, Rio Grande do Sul, Brazil, 95700-084
      • Active, not recruiting
      • Associacao Dr Bartholomeu Tacchini
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Active, not recruiting
      • Hospital de Clínicas de Porto Alegre
    • Porto Alegre, Rio Grande do Sul, Brazil, 90110-270
      • Active, not recruiting
      • Centro Gaucho Integrado
  • Santa Catarina
    • Lages, Santa Catarina, Brazil, 88501-001
      • Active, not recruiting
      • Animi Unidade de Tratamento Oncologico
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Active, not recruiting
      • The Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Active, not recruiting
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Active, not recruiting
      • University Health Network-Princess Margaret Cancer Center
• Chile
  • Las Condes
    • Santiago, Las Condes, Chile, 7620157
      • Active, not recruiting
      • Hospital Clinico Universidad de Los Andes
  • Región de Valparaíso
    • Viña del Mar, Región de Valparaíso, Chile, 2540488
      • Active, not recruiting
      • Centro de Investigaciones Clinicas Viña del Mar
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 6681920
      • Active, not recruiting
      • Clínica Alemana de Santiago
    • Santiago, Santiago Metropolitan, Chile, 7500921
      • Active, not recruiting
      • Fundacion Arturo Lopez Perez
    • Santiago, Santiago Metropolitan, Chile, 7550000
      • Active, not recruiting
      • Clínica UC San Carlos de Apoquindo
    • Santiago, Santiago Metropolitan, Chile, 7560907
      • Active, not recruiting
      • Centro Oncologia de Precision Universidad Mayor
• France
  • Paris, France, 75010
    • Completed
    • Hopital Saint Louis, APHP
  • Paris, France, 75571
    • Completed
    • Saint Antoine Hospital
  • Saint-Cloud, France, 92210
    • Completed
    • Institut Curie
  • Auvergne-Rhone
    • Lyon, Auvergne-Rhone, France, 69008
      • Active, not recruiting
      • Centre Leon Berard (CLB) - Centre de Recherche en Cancerologie Lyon-Est (CRCL)
  • Gironde
    • Pessac, Gironde, France, 33600
      • Active, not recruiting
      • Centre Francois Magendie
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59037
      • Withdrawn
      • Centre Hospitalier Universitaire De Lille
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75015
      • Active, not recruiting
      • Hopital Necker
    • Villejuif, Île-de-France Region, France, 94800
      • Active, not recruiting
      • Gustave Roussy
• Germany
  • Hamburg, Germany, 20246
    • Active, not recruiting
    • University Hospital Hamburg Eppendorf
  • Leipzig, Germany, 4103
    • Withdrawn
    • University Hospital Leipzig - Hematology and Cellular Therapy
  • Baden-Wurttemberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Active, not recruiting
      • Medical Clinic II
  • Ratzeburger
    • Lübeck, Ratzeburger, Germany, 23538
      • Active, not recruiting
      • Universitat zu Lubeck Neuromuskulares Zentrum
• Israel
  • Haifa, Israel, 3436212
    • Active, not recruiting
    • Lady Davis Carmel Medical Center
  • Jerusalem, Israel, 91120
    • Active, not recruiting
    • Hadassah Medical Center
  • Jerusalem, Israel, 9103102
    • Active, not recruiting
    • Shaare Zedek Medical Center
  • Ramat Gan, Israel, 52621
    • Active, not recruiting
    • Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Active, not recruiting
    • The Tel Aviv Sourasky Medical Center
  • North
    • Haifa, North, Israel, 3109601
      • Active, not recruiting
      • Rambam Health Care Campus
• Italy
  • Ancona, Italy, 60126
    • Active, not recruiting
    • AOU Ospedali Riuniti di Ancona
  • Bologna, Italy, 40138
    • Withdrawn
    • Policlinico S. Orsola- Malpighi
  • Catania, Italy, 95123
    • Active, not recruiting
    • Azienda Ospedaliero Universitaria Policlinico "G. Rodolico - San Marco"
  • Pavia, Italy, 27100
    • Active, not recruiting
    • Universita degli Studi di Pavia - Fondazione IRCCS Policlini
  • Ravenna, Italy, 48121
    • Active, not recruiting
    • Ospedale Santa Maria delle Croci
  • Reggio Emilia, Italy, 42123
    • Active, not recruiting
    • AUSL IRCCS OF Reggio Emilia - Clinical Study Location -
  • Varese, Italy, 21100
    • Active, not recruiting
    • Ospedale di Circolo e Fondazione Macchi Varese
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • Active, not recruiting
      • IRCCS Casa Sollievo della Sofferenza
  • Forli-Cesena
    • Meldola, Forli-Cesena, Italy, 47014
      • Active, not recruiting
      • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
  • Genova
    • Genoa, Genova, Italy, 16132
      • Active, not recruiting
      • Ospedale Policlinico San Martino IRCCS
  • Piedmont
    • Alessandria, Piedmont, Italy, 15121
      • Active, not recruiting
      • Azienda Ospedaliera Nazionale SS - Antonio e Biagio e Cesare Arrigo
    • Turin, Piedmont, Italy, 10126
      • Active, not recruiting
      • A.O.U. Città della Salute e Della Scienza di Torino
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Active, not recruiting
      • IRCCS Fondazione Piemontese Oncologica Candiolo
• Japan
  • Fukushima, Japan, 960-1295
    • Recruiting
    • Fukushima Medical University
  • Sendai, Japan, 983-8520
    • Recruiting
    • National Hospital Organization Sendai Medical Center
  • Aichi-ken
    • Nagakute, Aichi-ken, Japan, 480-1195
      • Recruiting
      • Aichi Medial University Hospital
  • Chiba
    • Chiba, Chiba, Japan, 260-8717
      • Recruiting
      • Chiba Cancer Center
    • Kamogawa, Chiba, Japan, 296-8602
      • Recruiting
      • Kameda General Hospital
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Recruiting
      • Kurume University Hospital
  • Gifu
    • Ōgaki, Gifu, Japan, 503-8502
      • Recruiting
      • Ogaki Municipal Hospital
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
      • Recruiting
      • Gunma University Hospital
    • Shibukawa, Gunma, Japan, 377-0280
      • Recruiting
      • NHO Shibukawa Medical Center
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0006
      • Recruiting
      • Sapporo Hokuyu Hospital
  • Iwate
    • Yahaba, Iwate, Japan, 028-3694
      • Recruiting
      • Iwate Medical University Hospital
  • Kumamoto
    • Kumamoto, Kumamoto, Japan, 860-0008
      • Recruiting
      • National Hospital Organization Kumamoto Medical Center
  • Okayama-ken
    • Kita-ku, Okayama-ken, Japan, 701-1192
      • Recruiting
      • National Hospital Organization Okayama Medical Center
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0871
      • Recruiting
      • Osaka University Hospital
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Recruiting
      • Saitama Medical University Hospital
  • Tokushima
    • Tokushima, Tokushima, Japan, 770-8539
      • Recruiting
      • Tokushima Prefectural Central Hospital
  • Tokyo
    • Shibuya-ku, Tokyo, Japan, 150-8935
      • Recruiting
      • Japanese Red Cross Medical Center
  • Yamanashi
    • Kofu, Yamanashi, Japan, 400-8506
      • Recruiting
      • Yamanashi Prefectural Central Hospital
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500HB
      • Active, not recruiting
      • Radboudumc
  • South Holland
    • Dordrecht, South Holland, Netherlands, 3318 AT
      • Active, not recruiting
      • Albert Schweitzer Hospital
• Poland
  • Bydgoszcz, Poland, 85-168
    • Completed
    • Szpital Uniwersytecki Nr2 Bydgoszcz
  • Katowice, Poland, 40-519
    • Active, not recruiting
    • Pratia Onkologia Katowice
  • Lublin, Poland, 20-954
    • Active, not recruiting
    • Centrum Innowacyjnych Terapii Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-219
      • Active, not recruiting
      • University Clinical Center / Medical University of Gdansk
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 93-510
      • Active, not recruiting
      • Wielospecjalistyczne Centrum Onkologii i Traumatologii
• Singapore
  • Singapore, Singapore, 169608
    • Active, not recruiting
    • Singapore General Hospital
  • Singapore, Singapore, 119074
    • Active, not recruiting
    • National University Hospital
• South Korea
  • Busan, South Korea, 49241
    • Active, not recruiting
    • Pusan National University Hospital
  • Busan, South Korea, 47392
    • Active, not recruiting
    • Inje University Busan Paik Hospital
  • Seoul, South Korea, 05505
    • Active, not recruiting
    • Asan Medical Center
  • Seoul, South Korea, 6351
    • Active, not recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 137-701
    • Active, not recruiting
    • Seoul St Marys Hospital
  • Seoul, South Korea, 744
    • Active, not recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 82
    • Active, not recruiting
    • Severance Hospital
  • Gyeonggi-do
    • Incheon, Gyeonggi-do, South Korea, 21565
      • Active, not recruiting
      • Gachon University Gil Hospital
  • Jeollabuk-do
    • Jeonju, Jeollabuk-do, South Korea, 54907
      • Active, not recruiting
      • Jeonbuk National University Hospital
  • Jeollanam-do
    • Hwasun, Jeollanam-do, South Korea, 58128
      • Active, not recruiting
      • Chonnam National University Hwasun Hospital
• Spain
  • Barcelona, Spain, 08036
    • Active, not recruiting
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08908
    • Recruiting
    • Catalan Institute of Oncology (ICO) Hospitalet
  • Barcelona, Spain, 08041
    • Withdrawn
    • Hospital Sant Pau
  • Girona, Spain, 17007
    • Active, not recruiting
    • Instituto Catalan Oncologia
  • Madrid, Spain, 28040
    • Active, not recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28046
    • Active, not recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28027
    • Withdrawn
    • Clinica Universidad de Navarra - Madrid
  • Málaga, Spain, 29010
    • Active, not recruiting
    • Hospital Virgen de la Victoria
  • Seville, Spain, 41014
    • Active, not recruiting
    • Hospital Universitario Virgen de Valme
  • Valencia, Spain, 46026
    • Withdrawn
    • Hospital Universitari i Politecnic La Fe
  • Zaragoza, Spain, 50009
    • Active, not recruiting
    • Hospital Clinico Lozano Blesa
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15706
      • Withdrawn
      • Hospital Clinico Universitario Santiago de Compostela
  • Alava
    • Vitoria-Gasteiz, Alava, Spain, 01009
      • Active, not recruiting
      • Hospital Universitario Araba
  • Balearic Islands
    • Palma, Balearic Islands, Spain, 07120
      • Active, not recruiting
      • Hospital Universitari Son Espases
    • Palma Mallorca, Balearic Islands, Spain, 07198
      • Active, not recruiting
      • Hospital Universitari Son LLàtzer
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Active, not recruiting
      • Institut Catala D'oncologia
    • Terrassa, Barcelona, Spain, 08221
      • Active, not recruiting
      • Hospital Universitari Mutua Terrassa
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Active, not recruiting
      • Hospital Universitario Marqués de Valdecilla
  • Castille and León
    • León, Castille and León, Spain, 24070
      • Active, not recruiting
      • Complejo Asistencial Universitario de Leon
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Withdrawn
      • Hospital Universitario Puerta de Hierro
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Active, not recruiting
      • Hospital Universitario Quironsalud Madrid
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Withdrawn
      • Clinica Universidad de Navarra - Pamplona
    • Pamplona, Navarre, Spain, 31008
      • Active, not recruiting
      • Hospital Universitario de Navarra
  • Principality of Asturias
    • Gijón, Principality of Asturias, Spain, 33203
      • Active, not recruiting
      • University Hospital of Cabuenes
    • Oviedo, Principality of Asturias, Spain, 33011
      • Withdrawn
      • Hospital Universitario Central de Asturias
  • Salamanca
    • Madrid, Salamanca, Spain, 28006
      • Active, not recruiting
      • Universitary Hospital La Princesa
  • Valencia
    • Alicante, Valencia, Spain, 03010
      • Active, not recruiting
      • Hospital General Universitario Doctor Balmis Alicante
• Taiwan
  • Changhua, Taiwan, 50006
    • Active, not recruiting
    • Changhua Christian Hospital
  • Hualien City, Taiwan, 97002
    • Active, not recruiting
    • Hualien Tzu Chi Hospital
  • Kaohsiung City, Taiwan, 83301
    • Active, not recruiting
    • Kaohsiung Chang Gung Memorial Hospital
  • Kaohsiung City, Taiwan, 80756
    • Active, not recruiting
    • Kaohsiung Medical University Hospital
  • Taichung, Taiwan, 40705
    • Withdrawn
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 701
    • Active, not recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • Active, not recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11490
    • Active, not recruiting
    • Tri-Service General Hospital
  • Taipei, Taiwan, 00116
    • Active, not recruiting
    • Wanfang Hospital
  • Hunan Province
    • Taoyuan District, Hunan Province, Taiwan, 33305
      • Active, not recruiting
      • Chang Gung Memorial Hospital - Linkou Branch
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Active, not recruiting
    • Hammersmith Hospital
  • London, United Kingdom, EC1A 7BE
    • Active, not recruiting
    • Barts Health NHS Trust
  • London, United Kingdom, SE1 9RT
    • Active, not recruiting
    • Guy's & St Thomas' NHS Foundation Trust
  • London, United Kingdom, SW7 3RP
    • Active, not recruiting
    • Royal Marsden Hospital
  • Manchester, United Kingdom, M20 4BX
    • Withdrawn
    • The Christie NHS Foundation Trust
  • Cambrigeshire
    • Cambridge, Cambrigeshire, United Kingdom, CB2 0QQ
      • Active, not recruiting
      • Addenbrooke's Hospital
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Active, not recruiting
      • Western General Hospital
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
      • Active, not recruiting
      • Queen Elizabeth Hospital Birmingham
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Active, not recruiting
      • University of California Los Angeles (UCLA)
  • Florida
    • Gainesville, Florida, United States, 32611
      • Withdrawn
      • University of Florida Division of Sponsored Programs
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Active, not recruiting
      • University of Kentucky, Markey Cancer Center Clinical Research Organization
    • Louisville, Kentucky, United States, 40207
      • Active, not recruiting
      • Norton Cancer Institute
  • New York
    • Stony Brook, New York, United States, 11794
      • Active, not recruiting
      • Stony Brook University
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Active, not recruiting
      • Levine Cancer Center
    • Durham, North Carolina, United States, 27705
      • Withdrawn
      • Duke University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97227
      • Active, not recruiting
      • Kaiser Permanente Northwest
  • Texas
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98195
      • Active, not recruiting
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Age 18 years or older (or legal adult age in the country) at the time of the screening visit.
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Patients with ECOG 2 solely due to local symptoms of myeloma (eg. pain) may be allowed after discussion with the Medical Monitor.

3. Received at least 1 and no more than 4 prior lines of anti-neoplastic MM therapies, including lenalidomide and a proteasome inhibitor and demonstrated disease progression on or after the last therapy as defined by the 2016 IMWG criteria. Participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory, as described in the protocol.

   Note: Participants in Israel also must have previously received a CD38 antibody. Participants in the EU and the UK must have previously received 2 to 4 prior lines of therapy, including a CD38 antibody.

4. Patients must have measurable disease for response assessment as per the 2016 IMWG response assessment criteria, as described in the protocol
5. Adequate hematologic function and hepatic function within 7 days of randomization, as well as adequate renal and cardiac function and corrected calcium
6. Life expectancy of at least 6 months

Key Exclusion Criteria:

1. Diagnosis of plasma cell leukemia, amyloidosis, Waldenström macroglobulinemia, or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
2. Prior treatment with elotuzumab and/or pomalidomide
3. Participants with known MM brain lesions or meningeal involvement
4. Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter
5. History of allogeneic stem cell transplantation within 6 months, or autologous stem cell transplantation within 12 weeks of the start of study treatment. Participants who have received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease. Steroids at doses equivalent to suppletion doses may be acceptable.
6. Prior treatment with B-cell maturation antigen (BCMA) directed immunotherapies Note: BCMA antibody-drug conjugates are allowed.
7. History of progressive multifocal leukoencephalopathy (PML), known or suspected PML, or history of a neurocognitive condition or central nervous system (CNS) movement disorder (Parkinson's disease or Parkinsonism).
8. Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first administration of study drug
9. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); or another uncontrolled infection, as defined in the protocol 10 Cardiac ejection fraction <40%.

NOTE: Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Elotuzumab/Pomalidomide/Dexamethasone (EPd); Randomization 1:1	Drug: Elotuzumab; Elotuzumab will be administered by IV infusion; Other Names: Empliciti; Drug: Dexamethasone; Dexamethasone tablets/capsules will be administered PO and/or by IV infusion; Other Names: Decadron; Drug: Pomalidomide; Pomalidomide capsules will be administered by mouth (PO); Other Names: Pomalyst
Experimental: Linvoseltamab; Randomization 1:1	Drug: Linvoseltamab; REGN5458 will be administered by intravenous (IV) infusion; Other Names: REGN5458; Lynozyfic™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) response criteria determined by Independent Review Committee (IRC) in CD38 antibody exposed participants	Up to approximatively 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS per IMWG response criteria determined by IRC in all participants		Up to approximatively 5 years
OR of PR or better per IMWG response criteria as determined by the IRC in all participants		Up to approximatively 5 years
OR of VGPR or better per IMWG response criteria as determined by IRC in all participants		Up to approximatively 5 years
OR of CR or better per IMWG response criteria as determined by IRC in all participants		Up to approximatively 5 years
Incidence of MRD negative status in all participants		Up to approximatively 5 years
OS in all participants		Up to approximatively 5 years
Mean change in the worst pain score measured by BPI-SF Item 3 in all participants	The BPI-SF is a validated, self-administered questionnaire designed to measure a participant's perceived level of pain. The BPI-SF Item 3 uses a numeric rating scale to assess pain severity and pain interference in the past 24 hours. The numeric rating scale ranges from 0 (no pain) to 10 (worst imaginable pain), where higher scores indicate greater intensity of pain.	Baseline to week 12
Incidence TEAEs in all participants		Up to approximatively 5 years
Severity of TEAEs in all participants		Up to approximatively 5 years
Incidence of AESI in all participants		Up to approximatively 5 years
Severity AESI in all participants		Up to approximatively 5 years
Incidence of SAE in all participants		Up to approximatively 5 years
Severity of SAE in all participants		Up to approximatively 5 years
PFS per IMWG response criteria as determined by the investigator in all participants		Up to approximatively 5 years
OR of PR or better per IMWG response criteria as determined by the investigator in all participants		Up to approximatively 5 years
OR of VGPR or better per IMWG response criteria as determined by the investigator in all participants		Up to approximatively 5 years
OR of CR or better per IMWG response criteria as determined by the investigator in all participants		Up to approximatively 5 years
DoR as per IMWG response criteria as determined by the investigator in all participants		Up to approximatively 5 years
DoR as per IMWG response criteria as determined by the IRC in all participants		Up to approximatively 5 years
Duration of MRD negative status in the bone marrow in all participants		Up to approximatively 5 years
Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the investigator in all participants		Up to approximatively 5 years
Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the IRC in all participants		Up to approximatively 5 years
Concentration of linvoseltamab in the serum over time in all participants		Up to approximatively 5 years
Incidence of ADAs in all participants		Up to approximatively 5 years
Titer of ADAs in all participants		Up to approximatively 5 years
Incidence of Nabs to linvoseltamab over time in all participants		Up to approximatively 5 years
Proportion of Pain Responders in all participants	Defined by at least a 2-point reduction from baseline in the BPI-SF Item 3 without an increase in analgesic use using the modified Analgesic Quantification Algorithm (AQA).	At week 12
Change in patient-reported QoL, per EORTC QLQ-C30 in all participants	The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."	Baseline to week 12
Change in patient reported disease symptoms per EORTC QLQ-MY20 in all participants	The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems.	Baseline to week 12
Patient-Reported Outcomes in PGIS in all participants	The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe". The global anchor, PGIS will be used for interpretation of EORTC QLQ-C30, EORTC QLQ-MY20, and BPI-SF.	Baseline to week 12
Patient-Reported Outcomes in PGIC in all participants	The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change". The global anchor, PGIC will be used for interpretation of EORTC QLQ-C30, EORTC QLQ-MY20, and BPI-SF.	Baseline to week 12
Change in patient-reported general health status per EQ-5D-5L in all participants	The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.	Baseline to week 12
OR of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by IRC in CD38 antibody exposed participants		Up to approximatively 5 years
Incidence of minimal residual disease (MRD) negative status in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Overall Survival (OS) in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Mean change in the worst pain score measured by Brief Pain Inventory-Short Form (BPI-SF) Item 3 in participants previously exposed to CD38 antibodies	The BPI-SF is a validated, self-administered questionnaire designed to measure a participant's perceived level of pain. The BPI-SF Item 3 uses a numeric rating scale to assess pain severity and pain interference in the past 24 hours. The numeric rating scale ranges from 0 (no pain) to 10 (worst imaginable pain), where higher scores indicate greater intensity of pain.	Baseline to week 12
Incidence of treatment emergent adverse events (TEAEs) in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Severity of TEAEs in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Incidence of adverse events of special interest (AESI) in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Severity of AESI in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Incidence of Serious Adverse Events (SAE) in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Severity of SAE in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
PFS per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
OR of PR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
OR of VGPR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
OR of CR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Duration of Response (DoR) as per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
DoR as per IMWG response criteria as determined by the IRC in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Duration of MRD negative status in the bone marrow in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the IRC in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Concentration of linvoseltamab in the serum over time in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Incidence of antidrug antibodies (ADAs) in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Titer of ADAs in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Incidence of neutralizing antibodies (Nabs) to linvoseltamab over time in participants previously exposed to CD38 antibodies		Up to approximatively 5 years
Proportion of Pain Responders in participants previously exposed to CD38 antibodies	Defined by at least a 2-point reduction from baseline in the BPI-SF Item 3 without an increase in analgesic use using the modified Analgesic Quantification Algorithm (AQA).	At week 12
Change in patient-reported global health status/quality of life (QoL), per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in participants previously exposed to CD38 antibodies	The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."	Baseline to week 12
Change in patient reported disease symptoms per EORTC Quality of Life Questionnaire-Multiple Myeloma (MM) module 20 [QLQ-MY20]) in participants previously exposed to CD38 antibodies	The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems.	Baseline to week 12
Patient-Reported Outcomes in Patient Global Impression of Symptom Severity (PGIS) in participants previously exposed to CD38 antibodies	The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe". The global anchor, PGIS will be used for interpretation of EORTC QLQ-C30, EORTC QLQ-MY20, and BPI-SF.	Baseline to week 12
Patient-Reported Outcomes in Patient Global Impression of Change (PGIC) in participants previously exposed to CD38 antibodies	The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change". The global anchor, PGIC will be used for interpretation of EORTC QLQ-C30, EORTC QLQ-MY20, and BPI-SF.	Baseline to week 12
Change in patient-reported general health status per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L]) in participants previously exposed to CD38 antibodies	The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.	Baseline to week 12
Objective Response (OR) of Complete Response (CR) or better per IMWG response criteria as determined by IRC in CD38 antibody exposed participants		Up to approximatively 5 years
OR of Partial Response (PR) or better per IMWG response criteria as determined by the IRC in CD38 antibody exposed participants		Up to approximatively 5 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• Study Information Website

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2023
• Primary Completion (Estimated): April 19, 2033
• Study Completion (Estimated): April 19, 2033

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: February 6, 2023
• First Posted (Actual): February 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Lenalidomide; Proteasome inhibitor; BCMA X CD3 Bispecific Monoclonal Antibody; CD38 antibody
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Sulfur Compounds; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Sulfonic Acids; Sulfur Acids; Pregnadienetriols; Benzenesulfonates; Arylsulfonates; Arylsulfonic Acids; Dexamethasone; Calcium Dobesilate; pomalidomide; elotuzumab
• Other Study ID Numbers: R5458-ONC-2245; 2022-501396-62-00 (Registry Identifier: CTIS Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No