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)
2 other identifiers
interventional
410
18 countries
159
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Sep 2023
Longer than P75 for phase_3
159 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 6, 2023
CompletedFirst Posted
Study publicly available on registry
February 15, 2023
CompletedStudy Start
First participant enrolled
September 18, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 19, 2033
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 19, 2033
March 6, 2026
October 1, 2025
9.6 years
February 6, 2023
March 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (63)
PFS per IMWG response criteria determined by IRC in all participants
Up to approximatively 5 years
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 CR or better per IMWG response criteria as determined by IRC in all participants
Up to approximatively 5 years
Overall Survival (OS) in participants previously exposed to CD38 antibodies
Up to approximatively 5 years
OS in all participants
Up to approximatively 5 years
- +58 more secondary outcomes
Study Arms (2)
Linvoseltamab
EXPERIMENTALRandomization 1:1
Elotuzumab/Pomalidomide/Dexamethasone (EPd)
ACTIVE COMPARATORRandomization 1:1
Interventions
REGN5458 will be administered by intravenous (IV) infusion
Elotuzumab will be administered by IV infusion
Pomalidomide capsules will be administered by mouth (PO)
Dexamethasone tablets/capsules will be administered PO and/or by IV infusion
Eligibility Criteria
You may qualify if:
- Age 18 years or older (or legal adult age in the country) at the time of the screening visit.
- 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.
- 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.
- Patients must have measurable disease for response assessment as per the 2016 IMWG response assessment criteria, as described in the protocol
- Adequate hematologic function and hepatic function within 7 days of randomization, as well as adequate renal and cardiac function and corrected calcium
- Life expectancy of at least 6 months
You may not qualify if:
- Diagnosis of plasma cell leukemia, amyloidosis, Waldenström macroglobulinemia, or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- Prior treatment with elotuzumab and/or pomalidomide
- Participants with known MM brain lesions or meningeal involvement
- Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter
- 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.
- Prior treatment with B-cell maturation antigen (BCMA) directed immunotherapies Note: BCMA antibody-drug conjugates are allowed.
- 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).
- Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first administration of study drug
- 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%.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (159)
University of California Los Angeles (UCLA)
Los Angeles, California, 90095, United States
University of Florida Division of Sponsored Programs
Gainesville, Florida, 32611, United States
University of Kentucky, Markey Cancer Center Clinical Research Organization
Lexington, Kentucky, 40536, United States
Norton Cancer Institute
Louisville, Kentucky, 40207, United States
Stony Brook University
Stony Brook, New York, 11794, United States
Levine Cancer Center
Charlotte, North Carolina, 28204, United States
Duke University Medical Center
Durham, North Carolina, 27705, United States
Kaiser Permanente Northwest
Portland, Oregon, 97227, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Washington
Seattle, Washington, 98195, United States
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Icon Cancer Centre - Wesley
Auchenflower, Queensland, 4066, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Launceston General Hospital
Launceston, Tasmania, 7250, Australia
St Vincent's Hospital
Fitzroy, Victoria, 3065, Australia
University Hospital Geelong
Geelong, Victoria, 3220, Australia
Austin Hospital
Heidelberg, Victoria, 3084, Australia
One Clinical Research at Hollywood Private Hospital
Nedlands, Western Australia, 6009, Australia
Clinique Universitaire de Mont Godinne
Yvoir, Namur, 5530, Belgium
AZ Delta Algemeen Ziekenhuis Delta
Roeselare, West-Vlaanderen, 8800, Belgium
Ziekenhuis Netwerk Antwerpen Stuivenberg
Antwerp, 2060, Belgium
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
IDOR - Sao Rafael Salvador Bahia
Salvador, Estado de Bahia, 41253-190, Brazil
Hospital Erasto Gaertner
Curitiba, Paraná, 81520-060, Brazil
Associacao Dr Bartholomeu Tacchini
Bento Gonçalves, Rio Grande do Sul, 95700-084, Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
Centro Gaucho Integrado
Porto Alegre, Rio Grande do Sul, 90110-270, Brazil
Animi Unidade de Tratamento Oncologico
Lages, Santa Catarina, 88501-001, Brazil
Instituto Americas de Ensino e Pesquisa
Rio de Janeiro, 22793-080, Brazil
A Beneficencia Portuguesa de Sao Paulo, Oncology House
São Paulo, 01321000, Brazil
Instituto DOr de Pesquisa e Ensino
São Paulo, 01401-002, Brazil
AC Camargo Cancer Center
São Paulo, 01509-010, Brazil
Clinica Medica Sao Germano
São Paulo, 04537-080, Brazil
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
University Health Network-Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9, Canada
Hospital Clinico Universidad de Los Andes
Santiago, Las Condes, 7620157, Chile
Centro de Investigaciones Clinicas Vina del Mar
Viña del Mar, Región de Valparaíso, 2540488, Chile
Clinica Alemana de Santiago
Santiago, Santiago Metropolitan, 6681920, Chile
Fundacion Arturo Lopez Perez
Santiago, Santiago Metropolitan, 7500921, Chile
Clinica UC San Carlos de Apoquindo
Santiago, Santiago Metropolitan, 7550000, Chile
Centro Oncologia de Precision Universidad Mayor
Santiago, Santiago Metropolitan, 7560907, Chile
Centre Leon Berard (CLB) - Centre de Recherche en Cancerologie Lyon-Est (CRCL)
Lyon, Auvergne-Rhone, 69008, France
Centre Francois Magendie
Pessac, Gironde, 33600, France
Centre Hospitalier Universitaire de Lille
Lille, Hauts-de-France, 59037, France
Hopital Saint Louis, APHP
Paris, 75010, France
Saint Antoine Hospital
Paris, 75571, France
Institut Curie
Saint-Cloud, 92210, France
Hopital Necker
Paris, Île-de-France Region, 75015, France
Gustave Roussy
Villejuif, Île-de-France Region, 94800, France
Medical Clinic II
Tübingen, Baden-Wurttemberg, 72076, Germany
Universitat zu Lubeck Neuromuskulares Zentrum
Lübeck, Ratzeburger, 23538, Germany
University Hospital Hamburg Eppendorf
Hamburg, 20246, Germany
University Hospital Leipzig - Hematology and Cellular Therapy
Leipzig, 4103, Germany
Rambam Health Care Campus
Haifa, North, 3109601, Israel
Lady Davis Carmel Medical Center
Haifa, 3436212, Israel
Shaare Zedek Medical Center
Jerusalem, 9103102, Israel
Hadassah Medical Center
Jerusalem, 91120, Israel
Sheba Medical Center
Ramat Gan, 52621, Israel
The Tel Aviv Sourasky Medical Center
Tel Aviv, 64239, Israel
IRCCS Casa Sollievo della Sofferenza
San Giovanni Rotondo, Foggia, 71013, Italy
Istituto Romagnolo per lo Studio Dei Tumori Dino Amadori
Meldola, Forli-Cesena, 47014, Italy
Ospedale Policlinico San Martino IRCCS
Genoa, Genova, 16132, Italy
Azienda Ospedaliera Nazionale SS - Antonio e Biagio e Cesare Arrigo
Alessandria, Piedmont, 15121, Italy
A.O.U. Citta della Salute e della Scienza di Torino
Turin, Piedmont, 10126, Italy
IRCCS Fondazione Piemontese Oncologica Candiolo
Candiolo, Torino, 10060, Italy
AOU Ospedali Riuniti di Ancona
Ancona, 60126, Italy
Policlinico S. Orsola- Malpighi
Bologna, 40138, Italy
Azienda Ospedaliero Universitaria Policlinico "G. Rodolico - San Marco"
Catania, 95123, Italy
Universita degli Studi di Pavia - Fondazione IRCCS Policlini
Pavia, 27100, Italy
Ospedale Santa Maria delle Croci
Ravenna, 48121, Italy
AUSL IRCCS OF Reggio Emilia - Clinical Study Location -
Reggio Emilia, 42123, Italy
Ospedale di Circolo e Fondazione Macchi Varese
Varese, 21100, Italy
Aichi Medial University Hospital
Nagakute, Aichi-ken, 480-1195, Japan
Chiba Cancer Center
Chiba, Chiba, 260-8717, Japan
Kameda General Hospital
Kamogawa, Chiba, 296-8602, Japan
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577, Japan
Kurume University Hospital
Kurume, Fukuoka, 830-0011, Japan
Ogaki Municipal Hospital
Ōgaki, Gifu, 503-8502, Japan
Gunma University Hospital
Maebashi, Gunma, 371-8511, Japan
NHO Shibukawa Medical Center
Shibukawa, Gunma, 377-0280, Japan
Sapporo Hokuyu Hospital
Sapporo, Hokkaido, 003-0006, Japan
Iwate Medical University Hospital
Yahaba, Iwate, 028-3694, Japan
National Hospital Organization Kumamoto Medical Center
Kumamoto, Kumamoto, 860-0008, Japan
National Hospital Organization Okayama Medical Center
Kita-ku, Okayama-ken, 701-1192, Japan
Osaka University Hospital
Suita-shi, Osaka, 565-0871, Japan
Saitama Medical University Hospital
Iruma-gun, Saitama, 350-0495, Japan
Tokushima Prefectural Central Hospital
Tokushima, Tokushima, 770-8539, Japan
Japanese Red Cross Medical Center
Shibuya-ku, Tokyo, 150-8935, Japan
Yamanashi Prefectural Central Hospital
Kofu, Yamanashi, 400-8506, Japan
Fukushima Medical University
Fukushima, 960-1295, Japan
National Hospital Organization Sendai Medical Center
Sendai, 983-8520, Japan
Radboudumc
Nijmegen, Gelderland, 6500HB, Netherlands
Albert Schweitzer Hospital
Dordrecht, South Holland, 3318 AT, Netherlands
University Clinical Center / Medical University of Gdansk
Gdansk, Pomeranian Voivodeship, 80-219, Poland
Szpital Uniwersytecki Nr2 Bydgoszcz
Bydgoszcz, 85-168, Poland
Pratia Onkologia Katowice
Katowice, 40-519, Poland
Centrum Innowacyjnych Terapii Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
Lublin, 20-954, Poland
Wielospecjalistyczne Centrum Onkologii i Traumatologii
Lodz, Łódź Voivodeship, 93-510, Poland
National University Hospital
Singapore, 119074, Singapore
Singapore General Hospital
Singapore, 169608, Singapore
Gachon University Gil Hospital
Incheon, Gyeonggi-do, 21565, South Korea
Jeonbuk National University Hospital
Jeonju, Jeollabuk-do, 54907, South Korea
Chonnam National University Hwasun Hospital
Hwasun, Jeollanam-do, 58128, South Korea
Inje University Busan Paik Hospital
Busan, 47392, South Korea
Pusan National University Hospital
Busan, 49241, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Seoul St Marys Hospital
Seoul, 137-701, South Korea
Samsung Medical Center
Seoul, 6351, South Korea
Seoul National University Hospital
Seoul, 744, South Korea
Severance Hospital
Seoul, 82, South Korea
Hospital Clinico Universitario Santiago de Compostela
Santiago de Compostela, A Coruna, 15706, Spain
Hospital Universitario Araba
Vitoria-Gasteiz, Alava, 01009, Spain
Hospital Universitari Son Espases
Palma, Balearic Islands, 07120, Spain
Hospital Universitari Son Llatzer
Palma Mallorca, Balearic Islands, 07198, Spain
Institut Catala d'Oncologia
Badalona, Barcelona, 08916, Spain
Hospital Universitari Mutua Terrassa
Terrassa, Barcelona, 08221, Spain
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008, Spain
Complejo Asistencial Universitario de Leon
León, Castille and León, 24070, Spain
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, 28222, Spain
Hospital Universitario Quironsalud Madrid
Pozuelo de Alarcón, Madrid, 28223, Spain
Clinica Universidad de Navarra - Pamplona
Pamplona, Navarre, 31008, Spain
Hospital Universitario de Navarra
Pamplona, Navarre, 31008, Spain
University Hospital of Cabuenes
Gijón, Principality of Asturias, 33203, Spain
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33011, Spain
Universitary Hospital La Princesa
Madrid, Salamanca, 28006, Spain
Hospital General Universitario Doctor Balmis Alicante
Alicante, Valencia, 03010, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital Sant Pau
Barcelona, 08041, Spain
Catalan Institute of Oncology (ICO) Hospitalet
Barcelona, 08908, Spain
Instituto Catalan Oncologia
Girona, 17007, Spain
Clinica Universidad de Navarra - Madrid
Madrid, 28027, Spain
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Virgen de la Victoria
Málaga, 29010, Spain
Hospital Universitario Virgen de Valme
Seville, 41014, Spain
Hospital Universitari i Politecnic La Fe
Valencia, 46026, Spain
Hospital Clinico Lozano Blesa
Zaragoza, 50009, Spain
Chang Gung Memorial Hospital - Linkou Branch
Taoyuan District, Hunan Province, 33305, Taiwan
Changhua Christian Hospital
Changhua, 50006, Taiwan
Hualien Tzu Chi Hospital
Hualien City, 97002, Taiwan
Kaohsiung Medical University Hospital
Kaohsiung City, 80756, Taiwan
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301, Taiwan
Taichung Veterans General Hospital
Taichung, 40705, Taiwan
National Cheng Kung University Hospital
Tainan, 701, Taiwan
Wanfang Hospital
Taipei, 00116, Taiwan
National Taiwan University Hospital
Taipei, 10002, Taiwan
Tri-Service General Hospital
Taipei, 11490, Taiwan
Addenbrooke's Hospital
Cambridge, Cambrigeshire, CB2 0QQ, United Kingdom
Western General Hospital
Edinburgh, Scotland, EH4 2XU, United Kingdom
Queen Elizabeth Hospital Birmingham
Birmingham, West Midlands, B15 2TH, United Kingdom
Barts Health NHS Trust
London, EC1A 7BE, United Kingdom
Guy's & St Thomas' NHS Foundation Trust
London, SE1 9RT, United Kingdom
Royal Marsden Hospital
London, SW7 3RP, United Kingdom
Hammersmith Hospital
London, W12 0HS, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trial Management
Regeneron Pharmaceuticals
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 6, 2023
First Posted
February 15, 2023
Study Start
September 18, 2023
Primary Completion (Estimated)
April 19, 2033
Study Completion (Estimated)
April 19, 2033
Last Updated
March 6, 2026
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- 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
- 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
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing