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NCT05137054RecruitingPhase 1

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

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

Source: ClinicalTrials.gov · Last updated 5 Nov 2026

Brief summary (registry, in English)

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). 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)

Status (registry)
Recruiting
Phase (registry)
Phase 1
Study type
Interventional
Enrollment
317 (estimated)
First submitted
18 Nov 2021
Start date
17 Aug 2022
Primary completion date
25 Mar 2028
Lead sponsor
Regeneron Pharmaceuticals
NCT number
NCT05137054
EU CT number
2023-506247-42-00
EudraCT number
2020-004638-39

What you commit to

  • Study type: Interventional · Phase 1
  • Planned participants: 317
  • From 17 Aug 2022 to the primary completion date, 25 Mar 2028
  • 41 sites in 6 countries
  • Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Criteria the registry did not label

  • General Key Inclusion Criteria:
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  • Participants must have measurable disease as defined in the protocol according to IMWG consensus criteria
  • Adequate creatinine clearance, hematologic function and hepatic function, as defined in protocol
  • 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:
  • 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
  • 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:
  • 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)
  • Participants with known MM brain lesions or meningeal involvement
  • 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
  • History of allogeneic and autologous stem cell transplantation, as described in the protocol
  • 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)
  • 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
  • Live or attenuated vaccination within 28 days prior to first study drug regimen administration with a vector that has replicative potential
  • 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:
  • 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
  • Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol
  • Prior solid organ transplant
  • 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:
  • 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
  • Encephalitis or meningitis in the year prior to enrollment
  • 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
  • Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol.
  • Prior solid organ transplant
  • 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:
  • Abnormal QT interval corrected by Fridericia's formula (QTcF), as described in the protocol
  • 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
  • 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
  • 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:
  • Known or suspected active Epstein-Barr Virus (EBV) infection
  • Known history of Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS)
  • 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

Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (41)

Sites in registry order. Pick your city on the disease page to sort them by distance.

SiteCityCountrySite status
Institut Catala d'Oncologia
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BadalonaSpainRecruiting
Hospital Clinic de Barcelona
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BarcelonaSpainRecruiting
Hospital Universitari Vall d'Hebron
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BarcelonaSpainRecruiting
Institut Catala D'oncologia
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L'Hospitalet de LlobregatSpainRecruiting
Hospital Universitario 12 de Octubre
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MadridSpainRecruiting
Hospital Universitario HM Sanchinarro
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MadridSpainRecruiting
Hospital Universitario Ramón y Cajal
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MadridSpainRecruiting
Hospital Universitario de la Princesa
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MadridSpainRecruiting
Clínica Universidad de navarra
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PamplonaSpainRecruiting
Hospital Universitario Quironsalud Madrid
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Pozuelo de AlarcónSpainRecruiting
Hospital Universitario De Salamanca
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SalamancaSpainRecruiting
Hospital Universitario Marqués de Valdecilla
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SantanderSpainRecruiting
Complexo Hospitalario Universitario De Santiago
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Santiago de CompostelaSpainRecruiting
Centre Hospitalier Universitaire D'Angers
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AngersFranceRecruiting
Assistance Publique Hopitaux De Paris
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Creteil CedexFranceRecruiting
Centre Hospitalier Universitaire de Lille
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LilleFranceRecruiting
Centre Hospitalier Universitaire De Montpellier
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Montpellier Cedex 5FranceRecruiting
Centre Hospitalier Universitaire de Nantes
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NantesFranceRecruiting
Assistance Publique Hopitaux de Paris
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ParisFranceRecruiting
Centre Hospitalier Universitaire de Poitiers
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PoitiersFranceRecruiting
Institut Gustave Roussy
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VillejuifFranceRecruiting
Alexandra Hospital
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AthensGreeceRecruiting
Evaggelismos Hospital
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AthensGreeceRecruiting
Rambam Health Care Campus
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HaifaIsraelRecruiting
Hadassah medical Center
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JerusalemIsraelRecruiting
Sheba medical center
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Ramat GanIsraelRecruiting
VUMC Stichting
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AmsterdamNetherlandsNot yet recruiting
Universitair Medisch Centrum Groningen
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GroningenNetherlandsNot yet recruiting
Winship Cancer Institute of Emory University
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AtlantaUnited StatesRecruiting
Dana-Farber Harvard Cancer Center
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BostonUnited StatesRecruiting
University of North Carolina at Chapel Hill
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Chapel HillUnited StatesRecruiting
The Ohio State University James Cancer Hospital
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ColumbusUnited StatesRecruiting
University of Texas, Southwestern
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DallasUnited StatesRecruiting
Karmanos Cancer Institute
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DetroitUnited StatesRecruiting
Indiana University Health Simon Cancer Center
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IndianapolisUnited StatesRecruiting
Scripps Clinic Torrey Pines
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La JollaUnited StatesRecruiting
Weill Cornell Medicine-New York Presbyterian Hospital
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New YorkUnited StatesRecruiting
New York Presbyterian Hospital-Columbia University Medical Center
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New YorkUnited StatesRecruiting
Mayo Clinic
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RochesterUnited StatesRecruiting
VA Puget Sound Health Care System
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SeattleUnited StatesRecruiting
Wake Forest University Health Sciences
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Winston-SalemUnited StatesRecruiting

This page is information, not medical advice. Discuss any trial with your doctor.