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Multiple MyelomaPhase 1NCT05137054

A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Participants With Multiple Myeloma That is Resistant to Current Standard of Care Treatments

A Phase 1 study testing Linvoseltamab, Daratumumab and Carfilzomib in people with Multiple Myeloma, run by Regeneron Pharmaceuticals at 42 sites in 5 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This study is researching an experimental drug called linvoseltamab in combination with other drugs for the treatment of a blood cancer called multiple myeloma. Linvoseltamab has previously been studied as a single agent (without other cancer treatments) in participants with multiple myeloma that returned after prior… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Linvoseltamab, Daratumumab and Carfilzomib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
317 participants
Where
42 sitesin 5 countries
Study dates
17 Aug 2022to 24 Mar 2032
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

General Key Inclusion Criteria:

  1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  2. Participants must have measurable disease as defined in the protocol according to IMWG consensus criteria
  3. Adequate creatinine clearance, hematologic function and hepatic function, as defined in protocol
  4. Life expectancy of at least 6 months

Cohort Specific Inclusion Criteria:

For cohorts 1-6, each participant must have RRMM with progression following at least 3 lines of therapy, or at least 2 lines of therapy and either prior exposure to at least 1 anti-CD38 antibody, 1 immunomodulatory imide drug (IMiD) and 1 Proteasome Inhibitor (PI), or double-refractory to 1 PI and 1 IMiD, or the combination of 1 PI and 1 IMiD Cohort 1: Prior treatment with daratumumab is allowed if previously tolerated, as described in the protocol Cohort 2: Prior treatment with carfilzomib is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 3: Prior treatment with lenalidomide is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 4: Prior treatment with bortezomib is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 5: Prior treatment with pomalidomide is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 6: Prior treatment with isatuximab is allowed if previously tolerated, as described in the protocol

Cohort 7 and 8:

  1. For participants without measurable disease by biochemical parameters [serum or urine M-protein, or serum involved Free Light Chain (FLC)], presence of at least 1 soft tissue plasmacytoma with a single diameter of ≥2 cm
  2. RRMM with progressive disease and received at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 IMiD, and 1 PI or triple-class refractory disease (anti-CD38 antibody, IMiD, PI) Cohort 9: Progressive RRMM in participants with triple-class refractory disease (anti-CD38 antibody, IMiD, PI) after at least 3 lines of therapy Cohort 10: Progressive RRMM after at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 IMiD, and 1 PI

General Key Exclusion Criteria:

  1. Diagnosis of plasma cell leukemia, primary light-chain amyloidosis (excluding myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes)
  2. Participants with known MM brain lesions or meningeal involvement
  3. Treatment with any systemic anti-myeloma therapy within 5 half-lives or within 21 days prior to first administration of study drug regimen, whichever is shorter
  4. History of allogeneic and autologous stem cell transplantation, as described in the protocol
  5. Unless stated otherwise in a specific sub-protocol, prior treatment with a T cell-based immunotherapy directed against B-Cell Maturation Antigen (BCMA) bispecific antibodies and Bispecific T-cell Engagers (BiTEs), and BCMA Chimeric Antigen Receptor (CAR) T cells (Note: BCMA antibody-drug conjugates are not excluded)
  6. History of progressive multifocal leukoencephalopathy, neurodegenerative condition or Central Nervous System (CNS) movement disorder or participants with a history of seizure within 12 months prior to study enrollment are excluded
  7. Live or attenuated vaccination within 28 days prior to first study drug regimen administration with a vector that has replicative potential
  8. Cardiac ejection fraction <40% by Echocardiogram (Echo) or Multigated Acquisition (MUGA) scan

Cohort Specific Exclusion Criteria:

Cohort 2: Dose expansion: Prior treatment with a BCMA-directed CAR T-cell therapy will not be exclusionary if completed at least 12 weeks prior to first study treatment Cohort 3: Known malabsorption syndrome or pre-existing gastrointestinal (GI) condition that may impair absorption of lenalidomide; delivery of lenalidomide via nasogastric tube or gastrostomy tube is not allowed Cohort 4: Peripheral neuropathy grade ≥2 Cohort 5: Known malabsorption syndrome or pre-existing GI conditions that may impair absorption of pomalidomide; delivery of pomalidomide via nasogastric tube or gastrostomy tube is not allowed

Cohort 7:

  1. Prior treatment with anti-Lymphocyte Activation Gene 3 (LAG-3) agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-Programmed cell Death Protein 1 (PD-1) antibodies is permitted, as described in the protocol
  2. Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol
  3. Prior solid organ transplant
  4. History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies

Cohort 8:

  1. Prior treatment with anti-PD-1 or anti-PD-L1 agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) antibodies is permitted, as described in the protocol
  2. Encephalitis or meningitis in the year prior to enrollment
  3. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to enrollment
  4. Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol.
  5. Prior solid organ transplant
  6. History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies

Cohort 9:

  1. Abnormal QT interval corrected by Fridericia's formula (QTcF), as described in the protocol
  2. Use of concomitant medications that are known to prolong the QT/QTcF interval including Class Ia and Class III antiarrhythmics at the time of informed consent
  3. Ongoing use or anticipated use of food or drugs that are known strong/moderate cytochrome P450 (CYP)3A4 inhibitors, or strong CYP3A inducers within 14 days prior to first dose of nirogacestat
  4. Known malabsorption syndrome or existing gastrointestinal GI condition that may impair absorption of nirogacestat; delivery of nirogacestat via nasogastric tube or gastrostomy tube is not allowed

Cohort 10:

  1. Known or suspected active Epstein-Barr Virus (EBV) infection
  2. Known history of Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS)
  3. Prior treatment with cevostamab or another agent with the same target [Fragment crystallizable Receptor-like 5 (FcRH5)]

Dose finding portion: Prior treatment with any BCMA-directed immunotherapy will not be exclusionary, as described in the protocol Dose expansion portion: Prior treatment with any T cell-engaging bispecific antibody directed against BCMA will be exclusionary, as described in the protocol

NOTE: Other protocol defined inclusion/exclusion criteria apply

Trial locations and contacts

42 sites in 5 countries. Contact the study team or a site near you to ask about taking part.

Clinical Trials Administrator contact

844-734-6643

clinicaltrials@regeneron.com

42 sites in 5 countries

Spain14 sites, 14 recruiting
  • Hospital Germans Trias i Pujol

    Badalona, Barcelona, 08916

    Recruiting
  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

    Recruiting
  • Hospital Clinic de Barcelona

    Barcelona, 08036

    Recruiting
  • Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals,

    Barcelona, 08908

    Recruiting
  • Universitaru Hospital La Princesa

    Madrid, 28006

    Recruiting
  • Clinica Universidad de Navarra - Madrid

    Madrid, 28027

    Recruiting
  • Hospital Universitario Ramon y Cajal - Servicio de Psiquiatria

    Madrid, 28034

    Recruiting
  • University Hospital and Research Institute

    Madrid, 28041

    Recruiting
  • Hospital Universitario HM Sanchinarro

    Madrid, 28050

    Recruiting
  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

    Recruiting
  • Hospital Universitario Quiron Salud Madrid

    Pozuelo de Alarcón, Madrid, 28223

    Recruiting
  • University Hospital of Salamanca

    Salamanca, 37007

    Recruiting
  • Hospital Universitario Marques de Valdecilla

    Santander, Cantabria, 39008

    Recruiting
  • Hospital Clinico Universitario de Santiago

    Santiago de Compostela, A Coruna, 15706

    Recruiting

Other trials in Spain

United States13 sites, 13 recruiting
  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30004

    Recruiting
  • Dana Farber/Harvard Cancer Center

    Boston, Massachusetts, 02215

    Recruiting
  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

    Recruiting
  • The Ohio State University James Cancer Hospital

    Columbus, Ohio, 43210

    Recruiting
  • University of Texas Southwestern

    Dallas, Texas, 75390

    Recruiting
  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

    Recruiting
  • Indiana University Health Simon Cancer Center

    Indianapolis, Indiana, 46202

    Recruiting
  • Scripps Clinic Torrey Pines

    La Jolla, California, 92037

    Recruiting
  • Weill Cornell Medicine/New York Presbyterian Hospital

    New York, New York, 10021

    Recruiting
  • New York Presbyterian Hospital Columbia University Medical Center

    New York, New York, 10032

    Recruiting
  • Mayo Clinic

    Rochester, Minnesota, 55905

    Recruiting
  • VA Puget Sound Health Care System

    Seattle, Washington, 98108

    Recruiting
  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

    Recruiting

Other trials in United States

France10 sites, 10 recruiting
  • Centre Hospitalier Universitaire Angers

    Angers, 49933

    Recruiting
  • Hospital Henri Mondor

    Créteil, Île-de-France Region, 94000

    Recruiting
  • CHU de Lille - Rue Michel Polonovski

    Lille, Nord, 59037

    Recruiting
  • CHU Montpellier - Departement D'Hematologie

    Montpellier, 34295

    Recruiting
  • Nantes University Hospital

    Nantes, Pays de la Loire Region, 44093

    Recruiting
  • Saint Antoine Hospital

    Paris, 75571

    Recruiting
  • Saint Louis Hospital

    Paris, Île-de-France Region, 75010

    Recruiting
  • Hopital Necker

    Paris, Île-de-France Region, 75015

    Recruiting
  • Centre Hospitalier Universitaire (CHU) de Poitiers

    Poitiers, New Aquitaine, 86021

    Recruiting
  • Institut Gustave Roussy

    Villejuif, 94805

    Recruiting

Other trials in France

Israel3 sites, 3 recruiting
  • Rambam Health Care Campus

    Haifa, 3109601

    Recruiting
  • Hadassah Medical Center

    Jerusalem, 91120

    Recruiting
  • Sheba Medical Center

    Ramat Gan, Central District, 5265601

    Recruiting

Other trials in Israel

Greece2 sites, 2 recruiting
  • Evangelismos General Hospital

    Athens, Attica, 10676

    Recruiting
  • General Hospital of Athens Alexandra

    Athens, 11528

    Recruiting

Other trials in Greece

About this study

Official title: Phase 1b Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) Plus Other Cancer Treatments for Patients With Relapsed/Refractory Multiple Myeloma

This study is researching an experimental drug called linvoseltamab in combination with other drugs for the treatment of a blood cancer called multiple myeloma. Linvoseltamab has previously been studied as a single agent (without other cancer treatments) in participants with multiple myeloma that returned after prior therapies and needed to be treated again.

In the initial study, some participants treated with linvoseltamab had improvement of their myeloma, including complete responses (no evidence of myeloma in their bodies).

Read more

This study is the first time linvoseltamab will be combined with other cancer therapies.

The main goal is to understand if linvoseltamab can be given safely with other cancer treatments, and if so, what dose of linvoseltamab should be used for each combination.

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

  • How many participants treated with linvoseltamab in combination with each of the other cancer treatments have improvement of their multiple myeloma
  • What side effects may happen from taking linvoseltamab together with another cancer treatment
  • How much study drug is in the blood at different times
  • Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) less effective or could lead to side effects)
Being tested
Linvoseltamab, Daratumumab, Carfilzomib, Lenalidomide, Bortezomib
Keywords
Relapsed/Refractory Multiple Myeloma (RRMM), B-cell maturation antigen (BCMA), Anti-CD3 monoclonal antibodies (mAbs)
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LinvoseltamabDrug

    Also called REGN5458, Lynozyfic™

    Administered per the protocol

  • DaratumumabDrug

    Also called Darzalex®; Darzalex Faspro™

    Administered per the protocol

  • CarfilzomibDrug

    Also called Kyprolis®

    Administered per the protocol

  • LenalidomideDrug

    Also called Revlimid®

    Administered per the protocol

  • BortezomibDrug

    Also called Velcade®

    Administered per the protocol

  • PomalidomideDrug

    Also called Imnovid, Pomalyst®

    Administered per the protocol

  • IsatuximabDrug

    Also called Sarclisa®

    Administered per the protocol

  • FianlimabDrug

    Also called REGN3767

    Administered per the protocol

  • CemiplimabDrug

    Also called LIBTAYO, REGN2810

    Administered per the protocol

  • NirogacestatDrug

    Also called PF-03084014

    Administered per the protocol

  • CevostamabDrug

    Also called BFCR4350A, RO7187797

    Administered per the protocol

Study groups in NCT05137054
Study groupRoleWhat they receive
Cohort 1: Linvoseltamab + DaratumumabExperimentalLinvoseltamab + Daratumumab
Receives: Drug: Linvoseltamab; Drug: Daratumumab
Cohort 2: Linvoseltamab + CarfilzomibExperimentalLinvoseltamab + Carfilzomib
Receives: Drug: Linvoseltamab; Drug: Carfilzomib
Cohort 3: Linvoseltamab + LenalidomideExperimentalLinvoseltamab + Lenalidomide
Receives: Drug: Linvoseltamab; Drug: Lenalidomide
Cohort 4: Linvoseltamab + BortezomibExperimentalLinvoseltamab + Bortezomib
Receives: Drug: Linvoseltamab; Drug: Bortezomib
Cohort 5: Linvoseltamab + PomalidomideExperimentalLinvoseltamab + Pomalidomide
Receives: Drug: Linvoseltamab; Drug: Pomalidomide
Cohort 6: Linvoseltamab + IsatuximabExperimentalLinvoseltamab + Isatuximab
Receives: Drug: Linvoseltamab; Drug: Isatuximab
Cohort 7: Linvoseltamab + FianlimabExperimentalLinvoseltamab + Fianlimab
Receives: Drug: Linvoseltamab; Drug: Fianlimab
Cohort 8: Linvoseltamab + CemiplimabExperimentalLinvoseltamab + Cemiplimab
Receives: Drug: Linvoseltamab; Drug: Cemiplimab
Cohort 9: Linvoseltamab + NirogacestatExperimentalLinvoseltamab + Nirogacestat
Receives: Drug: Linvoseltamab; Drug: Nirogacestat
Cohort 10: Linvoseltamab + CevostamabExperimentalLinvoseltamab + Cevostamab
Receives: Drug: Linvoseltamab; Drug: Cevostamab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Dose Limiting Toxicities (DLTs) for each study regimen during the observation period

    Dose finding portion only

    Measured: Up to 28 Days

  2. Incidence of Treatment-Emergent Adverse Events (TEAEs)

    Measured: Up to 5 Years

  3. Severity of TEAEs

    Measured: Up to 5 Years

  4. Incidence of Serious Adverse Events (SAEs)

    Measured: Up to 5 Years

  5. Severity of SAEs

    Measured: Up to 5 Years

  6. Incidence of Adverse Events of Special Interest (AESIs)

    Measured: Up to 5 Years

  7. Severity of AESIs

    Measured: Up to 5 Years

  8. Incidence of laboratory abnormalities

    ≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE v5.0]

    Measured: Up to 5 Years

Secondary outcomes (7)
  1. Overall Response Rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria

    Measured: Up to 5 Years

  2. Duration of Response (DOR) by IMWG criteria

    Measured: Up to 5 Years

  3. Progression-Free Survival (PFS) as measured by IMWG criteria

    Measured: Up to 5 Years

  4. Rate of Minimal Residual Disease (MRD) negative status by IMWG criteria

    Measured: Up to 5 Years

  5. Concentrations of total linvoseltamab in serum over time

    Measured: Up to 5 Years

  6. Incidence over time of Anti-Drug Antibodies (ADAs) to linvoseltamab

    Measured: Up to 5 Years

  7. Overall Survival (OS)

    Measured: Up to 5 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2021
  2. Study start17 Aug 2022
  3. Primary completion25 Mar 2028 (estimated)
  4. Study completion24 Mar 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
317 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05137054
Sponsor's protocol ID
R5458-ONC-2012
Other IDs
2020-004638-39, 2023-506247-42-00, 2023
Status last verified
Oct 2026
First submitted
18 Nov 2021
Last updated
5 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Linvoseltamab, Daratumumab and Carfilzomib in people with Multiple Myeloma, run by Regeneron Pharmaceuticals at 42 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in Spain, United States, France, Israel, Greece. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Clinical Trials Administrator (844-734-6643, clinicaltrials@regeneron.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Dose Limiting Toxicities (DLTs) for each study regimen during the observation period (time frame: Up to 28 Days). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.

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