Clinical trial Recruiting at 42 sites Phase 1 Interventional Ages 18 and up

Examining the effects of linvoseltamab with other cancer treatments for multiple myeloma

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

Run by Regeneron Pharmaceuticals · NCT05137054 · Data updated 2026-11-12

This study is testing a new drug called linvoseltamab along with other cancer treatments to see how well it works and how safe it is for adults with relapsed or refractory multiple myeloma.

More Multiple Myeloma trials

Quick facts

PhasePhase 1
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment317 (estimated)
SponsorRegeneron Pharmaceuticals
Industry-sponsored
Drugs / interventionsdaratumumab, isatuximab, cevostamab, CAR T, Chimeric Antigen Receptor, immunotherapy, radiation, linvoseltamab
Locations42 sites (La Jolla, California and 41 other locations)
StatusRecruiting
StartedAugust 17, 2022
Main results expectedMarch 25, 2028
Study endsMarch 24, 2032
Registry record updatedNovember 5, 2026
Trial IDNCT05137054 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates include adults with relapsed or refractory multiple myeloma who have undergone multiple lines of prior treatment.

Probably not a fit

Patients who have not received prior treatment for multiple myeloma or those with a performance status greater than 1 may not benefit from this study.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This study investigates the experimental drug linvoseltamab in combination with other cancer therapies for adult patients with relapsed or refractory multiple myeloma. The research aims to determine the safety and appropriate dosing of linvoseltamab when used alongside established treatments. Previous studies have shown that linvoseltamab can lead to improvements in myeloma, including complete responses. This is the first time linvoseltamab will be tested in combination with other therapies, providing valuable insights into its potential effectiveness. The study will also evaluate the response rates of participants receiving these combinations.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with multiple myeloma who have not responded to current therapies.

How similar studies have gone: Other studies have shown promising results with similar approaches, but this specific combination of linvoseltamab with other therapies is novel.

Who can join: the full rules

Show full inclusion / exclusion criteria
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

Where it's running

  • Scripps Clinic Torrey Pines
    La Jolla, California, United States
    Recruiting
  • Winship Cancer Institute of Emory University
    Atlanta, Georgia, United States
    Recruiting
  • Indiana University Health Simon Cancer Center
    Indianapolis, Indiana, United States
    Recruiting
  • Dana Farber/Harvard Cancer Center
    Boston, Massachusetts, United States
    Recruiting
  • Karmanos Cancer Institute
    Detroit, Michigan, United States
    Recruiting
  • Mayo Clinic
    Rochester, Minnesota, United States
    Recruiting
Show 36 more locations
  • Weill Cornell Medicine/New York Presbyterian Hospital
    New York, New York, United States
    Recruiting
  • New York Presbyterian Hospital Columbia University Medical Center
    New York, New York, United States
    Recruiting
  • University of North Carolina at Chapel Hill
    Chapel Hill, North Carolina, United States
    Recruiting
  • Wake Forest University Health Sciences
    Winston-Salem, North Carolina, United States
    Recruiting
  • The Ohio State University James Cancer Hospital
    Columbus, Ohio, United States
    Recruiting
  • University of Texas Southwestern
    Dallas, Texas, United States
    Recruiting
  • VA Puget Sound Health Care System
    Seattle, Washington, United States
    Recruiting
  • Centre Hospitalier Universitaire (CHU) de Poitiers
    Poitiers, New Aquitaine, France
    Recruiting
  • CHU de Lille - Rue Michel Polonovski
    Lille, Nord, France
    Recruiting
  • Nantes University Hospital
    Nantes, Pays de la Loire Region, France
    Recruiting
  • Centre Hospitalier Universitaire Angers
    Angers, France
    Recruiting
  • CHU Montpellier - Departement D'Hematologie
    Montpellier, France
    Recruiting
  • Saint Antoine Hospital
    Paris, France
    Recruiting
  • Institut Gustave Roussy
    Villejuif, France
    Recruiting
  • Hospital Henri Mondor
    Créteil, Île-de-France Region, France
    Recruiting
  • Saint Louis Hospital
    Paris, Île-de-France Region, France
    Recruiting
  • Hopital Necker
    Paris, Île-de-France Region, France
    Recruiting
  • Evangelismos General Hospital
    Athens, Attica, Greece
    Recruiting
  • General Hospital of Athens Alexandra
    Athens, Greece
    Recruiting
  • Sheba Medical Center
    Ramat Gan, Central District, Israel
    Recruiting
  • Rambam Health Care Campus
    Haifa, Israel
    Recruiting
  • Hadassah Medical Center
    Jerusalem, Israel
    Recruiting
  • Hospital Clinico Universitario de Santiago
    Santiago de Compostela, A Coruna, Spain
    Recruiting
  • Hospital Germans Trias i Pujol
    Badalona, Barcelona, Spain
    Recruiting
  • Hospital Universitario Marques de Valdecilla
    Santander, Cantabria, Spain
    Recruiting
  • Hospital Universitario Quiron Salud Madrid
    Pozuelo de Alarcón, Madrid, Spain
    Recruiting
  • Clinica Universidad de Navarra
    Pamplona, Navarre, Spain
    Recruiting
  • Hospital Universitario Vall d'Hebron
    Barcelona, Spain
    Recruiting
  • Hospital Clinic de Barcelona
    Barcelona, Spain
    Recruiting
  • Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals,
    Barcelona, Spain
    Recruiting
  • Universitaru Hospital La Princesa
    Madrid, Spain
    Recruiting
  • Clinica Universidad de Navarra - Madrid
    Madrid, Spain
    Recruiting
  • Hospital Universitario Ramon y Cajal - Servicio de Psiquiatria
    Madrid, Spain
    Recruiting
  • University Hospital and Research Institute
    Madrid, Spain
    Recruiting
  • Hospital Universitario HM Sanchinarro
    Madrid, Spain
    Recruiting
  • University Hospital of Salamanca
    Salamanca, Spain
    Recruiting

Study contacts

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.