A Study of Linvo-VR vs DVRd in Transplant-Eligible Adult Participants With Newly Diagnosed Multiple Myeloma (NDMM)

NCT07428369 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: R5458-HM-25042025-524032-19-00
• Study Type: interventional
• Target: 1,570
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is focused on participants with Newly Diagnosed Multiple Myeloma (NDMM) who are eligible for high dose chemotherapy followed by Autologous Stem Cell Transplantation (ASCT). This study is evaluating a drug called linvoseltamab in combination with standard therapies for multiple myeloma called bortezomib (V) and lenalidomide (R). This combination is abbreviated as Linvo-VR. The aim of this study is to compare how well Linvo-VR, with and without ASCT, treats myeloma to how well the current standard of care regimen for NDMM treats myeloma. That current standard of care regimen includes the drugs daratumumab (D), bortezomib (V), lenalidomide (R), and dexamethasone (d). This combination is referred to as DVRd. The study is also evaluating if Linvo-VR treats myeloma well enough that ASCT is no longer needed with the first myeloma treatments. The study is looking at several other research questions, including:

• What side effects may happen from taking linvoseltamab
• How much linvoseltamab is in the blood at different times
• Whether the body makes antibodies against the linvoseltamab (which could make the drug less effective or could lead to side effects)

Conditions

Multiple Myeloma (MM)

Keywords

Autologous Stem Cell Transplantation (ASCT); Transplant-Eligible; Linvoseltamab; Newly Diagnosed Multiple Myeloma (NDMM); High-dose chemotherapy; Bortezomib (V); Lenalidomide (R); Daratumumab (D), bortezomib (V), lenalidomide (R), dexamethasone (d) (DVRd)

Outcome Measures

Primary Outcomes (5)

• Occurrence of Treatment-Emergent Adverse Events (TEAEs)

  Phase 2

  Up to day 112

• Severity of TEAEs

  Phase 2

  Up to day 112

• Achievement of Complete Response or better (≥CR) per International Myeloma Working Group (IMWG) criteria

  Phase 2

  Up to day 112

• Minimal Residual Disease (MRD) negative CR at 10^-5 per IMWG criteria

  Phase 3

  Up to 12 months

• Progression Free Survival (PFS) per IMWG

  Phase 3

  Up to 5 years

Secondary Outcomes (69)

• Occurrence of TEAEs

  Up to 3.5 years

• Severity of TEAEs

  Up to 3.5 years

• Occurrence of Serious Adverse Events (SAEs)

  Up to 3.5 years

• Severity of SAEs

  Up to 3.5 years

• Occurrence of Cytokine Release Syndrome (CRS)

  Up to day 30

Study Arms (3)

Linvo-VR with ASCT

EXPERIMENTAL

Drug: Linvoseltamab; Drug: Bortezomib; Drug: Lenalidomide

Linvo-VR without ASCT

EXPERIMENTAL

Drug: Linvoseltamab; Drug: Bortezomib; Drug: Lenalidomide

DVRd with ASCT

ACTIVE COMPARATOR

Drug: Bortezomib; Drug: Lenalidomide; Drug: Daratumumab; Drug: Dexamethasone

Interventions

Linvoseltamab DRUG

Administered per the protocol

Also known as: REGN5458, Lynozyfic™

Linvo-VR with ASCT; Linvo-VR without ASCT

Bortezomib DRUG

Administered per the protocol

Also known as: Velcade®

DVRd with ASCT; Linvo-VR with ASCT; Linvo-VR without ASCT

Lenalidomide DRUG

Administered per the protocol

Also known as: Revlimid®

DVRd with ASCT; Linvo-VR with ASCT; Linvo-VR without ASCT

Daratumumab DRUG

Administered per the protocol

Also known as: Darzalex Faspro®,, Darzalex®

DVRd with ASCT

Dexamethasone DRUG

Administered per the protocol

Also known as: Dexahexal®,, Decadron®

DVRd with ASCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a histologically or cytologically confirmed diagnosis of multiple myeloma, which requires the presence of clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma, and at least one other criteria as defined by the SLiM (\>=60%, Light chains I/U \>10, Magnetic resonance imaging \>1 focal lesion) CRAB (Calcium elevation, Renal insufficiency, Anemia, Bone disease) criteria
• Participants must have measurable disease, as defined in the protocol
• Participants must be considered eligible for high-dose chemotherapy (melphalan) and ASCT per local standard guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Must be willing to defer ASCT

You may not qualify if:

• Any prior therapy for Monoclonal Gammopathy of Undetermined Significance (MGUS), Monoclonal Gammopathy of Renal Significance (MGRS), Smoldering Multiple Myeloma (SMM), or MM, with the exception of those defined in the protocol
• Participants who have received or are receiving any investigational agent or cell therapy with known or suspected activity against MM (or another plasma cell disorder), or those whose AEs due to agents administered earlier (such as radiation and/or corticosteroids) have not recovered to a severity of grade 0 or grade 1
• Participants with non-secretory MM, diagnosis of plasma cell leukemia (\>20% circulating plasma cells), symptomatic amyloidosis (including myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes).
• Participants who have known Central Nervous System (CNS) or meningeal involvement with MM or known or suspected Progressive Multifocal Leukoencephalopathy (PML), a history of a neurocognitive condition or CNS movement disorder, OR a history of seizure, Transient Ischemic Attack (TIA), or stroke within 12 months prior to study randomization
• Another malignancy besides MM that is progressive or has required treatment in the 3 years preceding randomization with the exceptions defined in the protocol

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Lenalidomide; daratumumab; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials Administrator

CONTACT

844-734-6643; clinicaltrials@regeneron.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2026
• First Posted: February 23, 2026
• Study Start: June 5, 2026
• Primary Completion (Estimated): May 21, 2038
• Study Completion (Estimated): May 21, 2038
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When Regeneron has: * received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development * made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry) * the legal authority to share the data, and * ensured the ability to protect participant privacy
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf