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.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 317 (estimated) |
| Sponsor | Regeneron Pharmaceuticals Industry-sponsored |
| Drugs / interventions | daratumumab, isatuximab, cevostamab, CAR T, Chimeric Antigen Receptor, immunotherapy, radiation, linvoseltamab |
| Locations | 42 sites (La Jolla, California and 41 other locations) |
| Status | Recruiting |
| Started | August 17, 2022 |
| Main results expected | March 25, 2028 |
| Study ends | March 24, 2032 |
| Registry record updated | November 5, 2026 |
| Trial ID | NCT05137054 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
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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
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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
- Study coordinator: Clinical Trials Administrator
- Email: clinicaltrials@regeneron.com
- Phone: 844-734-6643
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
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Linvoseltamab versus standard daratumumab‑lenalidomide‑dexamethasone for adults with newly diagnosed, transplant‑ineligible multiple myeloma
This trial tests whether linvoseltamab works better or is safer than the standard daratumumab‑lenalidomide‑dexamethasone combination in adults newly diagnosed with multiple myeloma who are not eligible for transplant.
-
Add linvoseltamab to lenalidomide maintenance to deepen responses and regain MRD-negative status in newly diagnosed multiple myeloma
This trial tests whether adding linvoseltamab to lenalidomide maintenance can clear remaining myeloma cells (make you MRD-negative) or help patients who relapsed get back to MRD-negative in newly diagnosed multiple myeloma.
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Using Linvoseltamab to treat newly diagnosed multiple myeloma
This study is testing if a new treatment called Linvoseltamab can help people with newly diagnosed multiple myeloma get rid of leftover cancer cells after their initial therapy.
-
Testing REGN5458 for patients with relapsed or refractory multiple myeloma
This study is testing a new drug called REGN5458 to see if it can safely help adults with relapsed or refractory multiple myeloma who have few treatment options.
-
6MW5311 in adults with relapsed or refractory blood cancers
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.