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NCT05730036PHASE3Recruiting

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

Regeneron Pharmaceuticals

Start Date

9/18/2023

Completion Date

4/19/2033

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

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Linvoseltamab

DRUG

Elotuzumab

DRUG

Pomalidomide

DRUG

Dexamethasone

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Conditions

Relapsed Refractory Multiple Myeloma (RRMM)

Locations

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

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

Centro de Investigaciones Clinicas Vina del Mar

Viña del Mar, Valparaiso 2540488

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, 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