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

Official title

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)

Overview

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

Interventions

• Drug Linvoseltamab
  REGN5458 will be administered by intravenous (IV) infusion
• Drug Elotuzumab
  Elotuzumab will be administered by IV infusion
• Drug Pomalidomide
  Pomalidomide capsules will be administered by mouth (PO)
• Drug Dexamethasone
  Dexamethasone tablets/capsules will be administered PO and/or by IV infusion

Primary outcome measures

• Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) response criteria determined by Independent Review Committee (IRC) in CD38 antibody exposed participants [Time frame: Up to approximatively 5 years]

Secondary outcome measures (12)

• PFS per IMWG response criteria determined by IRC in all participants [Time frame: 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 [Time frame: Up to approximatively 5 years]
• OR of CR or better per IMWG response criteria as determined by IRC in all participants [Time frame: Up to approximatively 5 years]
• Overall Survival (OS) in participants previously exposed to CD38 antibodies [Time frame: Up to approximatively 5 years]
• OS in all participants [Time frame: Up to approximatively 5 years]
• Incidence of minimal residual disease (MRD) negative status in participants previously exposed to CD38 antibodies [Time frame: Up to approximatively 5 years]
• Incidence of MRD negative status in all participants [Time frame: 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 [Time frame: Baseline to week 12]
• Mean change in the worst pain score measured by BPI-SF Item 3 in all participants [Time frame: Baseline to week 12]
• Incidence of treatment emergent adverse events (TEAEs) in participants previously exposed to CD38 antibodies [Time frame: Up to approximatively 5 years]
• Incidence TEAEs in all participants [Time frame: Up to approximatively 5 years]
• Severity of TEAEs in participants previously exposed to CD38 antibodies [Time frame: Up to approximatively 5 years]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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%.

NOTE: Other protocol defined inclusion/exclusion criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 27 centers

Center list to be confirmed — check the primary protocol.

Japan · 19 centers

• Aichi Medial University Hospital — Nagakute
• Chiba Cancer Center — Chiba
• Kameda General Hospital — Kamogawa
• National Cancer Center Hospital East — Kashiwa-shi
• … and 15 more centers

Italy · 13 centers

• IRCCS Casa Sollievo della Sofferenza — San Giovanni Rotondo
• Istituto Romagnolo per lo Studio Dei Tumori Dino Amadori — Meldola
• Ospedale Policlinico San Martino IRCCS — Genoa
• Azienda Ospedaliera Nazionale SS - Antonio e Biagio e Cesare Arrigo — Alessandria
• A.O.U. Citta della Salute e della Scienza di Torino — Turin
• IRCCS Fondazione Piemontese Oncologica Candiolo — Candiolo
• AOU Ospedali Riuniti di Ancona — Ancona
• Policlinico S. Orsola- Malpighi — Bologna
• … and 5 more centers

Australia · 11 centers

• Royal Prince Alfred Hospital — Camperdown
• Royal North Shore Hospital — St Leonards
• Icon Cancer Centre - Wesley — Auchenflower
• Royal Brisbane and Women's Hospital — Herston
• Royal Adelaide Hospital — Adelaide
• Royal Hobart Hospital — Hobart
• Launceston General Hospital — Launceston
• St Vincent's Hospital — Fitzroy
• … and 3 more centers

Brazil · 11 centers

• IDOR - Sao Rafael Salvador Bahia — Salvador
• Hospital Erasto Gaertner — Curitiba
• Associacao Dr Bartholomeu Tacchini — Bento Gonçalves
• Hospital de Clinicas de Porto Alegre — Porto Alegre
• Centro Gaucho Integrado — Porto Alegre
• Animi Unidade de Tratamento Oncologico — Lages
• Instituto Americas de Ensino e Pesquisa — Rio de Janeiro
• A Beneficencia Portuguesa de Sao Paulo, Oncology House — São Paulo
• … and 3 more centers

United States · 10 centers

• University of California Los Angeles (UCLA) — Los Angeles
• University of Florida Division of Sponsored Programs — Gainesville
• University of Kentucky, Markey Cancer Center Clinical Research Organization — Lexington
• Norton Cancer Institute — Louisville
• Stony Brook University — Stony Brook
• Levine Cancer Center — Charlotte
• Duke University Medical Center — Durham
• Kaiser Permanente Northwest — Portland
• … and 2 more centers

South Korea · 10 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 10 centers

Center list to be confirmed — check the primary protocol.

France · 8 centers

• Centre Leon Berard (CLB) - Centre de Recherche en Cancerologie Lyon-Est (CRCL) — Lyon
• Centre Francois Magendie — Pessac
• Centre Hospitalier Universitaire de Lille — Lille
• Hopital Saint Louis, APHP — Paris
• Saint Antoine Hospital — Paris
• Institut Curie — Saint-Cloud
• Hopital Necker — Paris
• Gustave Roussy — Villejuif

United Kingdom · 8 centers

Center list to be confirmed — check the primary protocol.

Chile · 6 centers

• Hospital Clinico Universidad de Los Andes — Santiago
• Clinica Alemana de Santiago — Santiago
• Fundacion Arturo Lopez Perez — Santiago
• Clinica UC San Carlos de Apoquindo — Santiago
• Centro Oncologia de Precision Universidad Mayor — Santiago
• Centro de Investigaciones Clinicas Vina del Mar — Viña del Mar

Israel · 6 centers

• Rambam Health Care Campus — Haifa
• Lady Davis Carmel Medical Center — Haifa
• Shaare Zedek Medical Center — Jerusalem
• Hadassah Medical Center — Jerusalem
• Sheba Medical Center — Ramat Gan
• The Tel Aviv Sourasky Medical Center — Tel Aviv

Poland · 5 centers

Center list to be confirmed — check the primary protocol.

Belgium · 4 centers

• Clinique Universitaire de Mont Godinne — Yvoir
• AZ Delta Algemeen Ziekenhuis Delta — Roeselare
• Ziekenhuis Netwerk Antwerpen Stuivenberg — Antwerp
• Cliniques Universitaires Saint-Luc — Brussels

Germany · 4 centers

• Medical Clinic II — Tübingen
• Universitat zu Lubeck Neuromuskulares Zentrum — Lübeck
• University Hospital Hamburg Eppendorf — Hamburg
• University Hospital Leipzig - Hematology and Cellular Therapy — Leipzig

Canada · 3 centers

• The Ottawa Hospital Cancer Centre — Ottawa
• Sunnybrook Health Sciences Centre — Toronto
• University Health Network-Princess Margaret Cancer Center — Toronto

Netherlands · 2 centers

Center list to be confirmed — check the primary protocol.

Singapore · 2 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05730036 · R5458-ONC-2245 · 2022-501396-62-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗