A Study of Linvo-VR vs DVRd in Transplant-Eligible Adult Participants With Newly Diagnosed Multiple Myeloma (NDMM) (LINKER-MM8)

A Phase 2/3, Open-Label, Randomized Study of Linvoseltamab, Bortezomib and Lenalidomide (Linvo-VR) With and Without Autologous Stem Cell Transplantation (ASCT) Vs Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) in Transplant-Eligible Participants With Newly Diagnosed Multiple Myeloma

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)

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma (MM)
• Intervention / Treatment: Drug: Daratumumab; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Linvoseltamab; Drug: Bortezomib

• Study Type: Interventional
• Enrollment (Estimated): 1570
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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
2. Participants must have measurable disease, as defined in the protocol
3. Participants must be considered eligible for high-dose chemotherapy (melphalan) and ASCT per local standard guidelines
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2
5. Must be willing to defer ASCT

Key Exclusion Criteria:

1. 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
2. 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
3. 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).
4. 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
5. Another malignancy besides MM that is progressive or has required treatment in the 3 years preceding randomization with the exceptions defined in the protocol

NOTE: Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Linvo-VR with ASCT	Drug: Lenalidomide; Administered per the protocol; Other Names: Revlimid®; Drug: Linvoseltamab; Administered per the protocol; Other Names: REGN5458; Lynozyfic™; Drug: Bortezomib; Administered per the protocol; Other Names: Velcade®
Experimental: Linvo-VR without ASCT	Drug: Lenalidomide; Administered per the protocol; Other Names: Revlimid®; Drug: Linvoseltamab; Administered per the protocol; Other Names: REGN5458; Lynozyfic™; Drug: Bortezomib; Administered per the protocol; Other Names: Velcade®
Active Comparator: DVRd with ASCT	Drug: Daratumumab; Administered per the protocol; Other Names: Darzalex®; Darzalex Faspro®,; Drug: Lenalidomide; Administered per the protocol; Other Names: Revlimid®; Drug: Dexamethasone; Administered per the protocol; Other Names: Decadron®; Dexahexal®,; Drug: Bortezomib; Administered per the protocol; Other Names: Velcade®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		Up to 5 years
Time to Very Good Partial Response or better (≥VGPR) per IMWG criteria		Up to 5 years
Time to ≥CR per IMWG criteria		Up to 5 years
Occurrence of TEAEs	Phase 2	Up to 3.5 years
Severity of TEAEs	Phase 2	Up to 3.5 years
Occurrence of Serious Adverse Events (SAEs)	Phase 2	Up to 3.5 years
Severity of SAEs	Phase 2	Up to 3.5 years
Occurrence of Cytokine Release Syndrome (CRS)	Phase 2	Up to day 30
Severity of CRS	Phase 2	Up to day 30
Occurrence of Cell-Associated Neurotoxicity Syndrome (ICANS)	Phase 2	Up to day 30
Severity of ICANS	Phase 2	Up to day 30
Achievement of objective response [Partial Response or better (≥PR)] per IMWG criteria		Up to 5 years
Time to ≥PR per IMWG criteria		Up to 5 years
Achievement of MRD negative (at 10^-5 sensitivity) CR per IMWG criteria		Up to 5 years
Duration Of Response (DOR) of ≥PR per IMWG criteria		Up to 5 years
Duration of ≥VGPR per IMWG criteria		Up to 5 years
Duration of ≥CR per IMWG criteria		Up to 5 years
PFS per IMWG criteria		Up to 5 years
Second PFS (PFS2) per IMWG criteria		Up to 5 years
Concentrations of total linvoseltamab in serum		Up to 5 years
Occurrence of TEAEs	Phase 3	Up to 5 years
Severity of TEAEs	Phase 3	Up to 5 years
Occurrence of SAEs	Phase 3	Up to 5 years
Severity of SAEs	Phase 3	Up to 5 years
Occurrence of second primary malignancies	Phase 3	Up to 5 years
Change from baseline in Global Health Status (GHS) per European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30)	Phase 3 The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported Quality of Life (QoL). For GHS, scores range from 1 = "very poor" to 5 = "excellent" with higher scores indicating better functioning and positive changes from baseline indicate improvement.	Up to 5 years
Change from baseline in physical functioning per EORTC QLQ-C30	Phase 3 The EORTC QLQ-C30 is a validated 30-item questionnaire designed to measure patient-reported quality of life. Physical functioning is scored from 1 'very poor' to 5 'excellent,' with higher scores indicating better functioning; positive changes from baseline indicate improvement.	Up to 5 years
Change from baseline in role functioning per EORTC QLQ-C30	Phase 3 The EORTC QLQ-C30 is a validated 30-item questionnaire designed to measure patient-reported quality of life. Role functioning is scored from 1 'very poor' to 5 'excellent,' with higher scores indicating better functioning; positive changes from baseline indicate improvement.	Up to 5 years
Change from baseline in pain per EORTC QLQ-C30	Phase 3 The EORTC QLQ-C30 is a validated 30-item questionnaire designed to measure patient-reported quality of life. Pain is scored from 1 = "not at all" to 9 = "very much". Higher scores indicate higher symptom burden.	Up to 5 years
Change from baseline in fatigue per EORTC QLQ-C30	Phase 3 The EORTC QLQ-C30 is a validated 30-item questionnaire designed to measure patient-reported quality of life. Fatigue is scored from1 = "not at all" to 9 = "very much". Higher scores indicate higher symptom burden.	Up to 5 years
Change from baseline in disease symptoms per EORTC QLQ- Multiple Myeloma Module 20 (MY20)	Phase 3 The EORTC QLQ-MY20 is a self-administered instrument to assess QoL in persons with MM. This 20-item questionnaire includes 6 items for disease symptoms. A high score for a symptom scale/item represents a high level of symptomatic problem.	Up to 5 years
Change from baseline in treatment side effects per EORTC QLQ-MY20	Phase 3 The EORTC QLQ-MY20 is a self-administered instrument to assess QoL in persons with MM. This 20-item questionnaire includes 10 items for treatment side effects. A high score for a symptom scale/item represents a high level of symptomatic problem.	Up to 5 years
Change from baseline in body image per EORTC QLQ-MY20	Phase 3 The EORTC QLQ-MY20 is a self-administered instrument to assess QoL in persons with MM. This 20-item questionnaire includes 1 item for treatment body image. A high score for a symptom scale/item represents a high level of symptomatic problem.	Up to 5 years
Change from baseline in future perspective per EORTC QLQ-MY20	Phase 3 The EORTC QLQ-MY20 is a self-administered instrument to assess QoL in persons with MM. This 20-item questionnaire includes 3 items for treatment future perspective. A high score for a symptom scale/item represents a high level of symptomatic problem.	Up to 5 years
Change from baseline in EuroQoL-5 Dimensions 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS)	Phase 3 The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: "no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems". The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labeled "Best imaginable health state" and "Worst imaginable health state".	Up to 5 years
Time to definitive deterioration in GHS per EORTC QLQ-C30	Phase 3	Up to 5 years
Time to definitive deterioration in physical functioning per EORTC QLQ-C30	Phase 3	Up to 5 years
Time to definitive deterioration in role functioning per EORTC QLQ-C30	Phase 3	Up to 5 years
Time to definitive deterioration in pain per EORTC QLQ-C30	Phase 3	Up to 5 years
Time to definitive deterioration in fatigue per EORTC QLQ-C30	Phase 3	Up to 5 years
Time to definitive deterioration in disease symptoms per EORTC QLQ-MY20	Phase 3	Up to 5 years
Time to definitive deterioration in treatment side effects per EORTC QLQ-MY20	Phase 3	Up to 5 years
Time to definitive deterioration in body image per EORTC QLQ-MY20	Phase 3	Up to 5 years
Time to definitive deterioration in future perspective per EORTC QLQ-MY20	Phase 3	Up to 5 years
Time to definitive deterioration in EQ-5D-5L VAS	Phase 3	Up to 5 years
Time to first improvement in GHS per EORTC QLQ-C30	Phase 3	Up to 5 years
Time to first improvement in physical functioning per EORTC QLQ-C30	Phase 3	Up to 5 years
Time to first improvement in role functioning per EORTC QLQ-C30	Phase 3	Up to 5 years
Time to first improvement in pain per EORTC QLQ-C30	Phase 3	Up to 5 years
Time to first improvement in fatigue per EORTC QLQ-C30	Phase 3	Up to 5 years
Time to first improvement in disease symptoms per EORTC QLQ-MY20	Phase 3	Up to 5 years
Time to first improvement in treatment side effects per EORTC QLQ-MY20	Phase 3	Up to 5 years
Time to first improvement in body image per EORTC QLQ-MY20	Phase 3	Up to 5 years
Time to first improvement in future perspective per EORTC QLQ-MY20	Phase 3	Up to 5 years
Time to first improvement in EQ-5D-5L VAS	Phase 3	Up to 5 years
Proportion with clinically meaningful improvement in GHS per EORTC QLQ-C30	Phase 3	Up to 5 years
Proportion with clinically meaningful improvement in physical functioning per EORTC QLQ-C30	Phase 3	Up to 5 years
Proportion with clinically meaningful improvement in role functioning per EORTC QLQ-C30	Phase 3	Up to 5 years
Proportion with clinically meaningful improvement in pain per EORTC QLQ-C30	Phase 3	Up to 5 years
Proportion with clinically meaningful improvement in fatigue per EORTC QLQ-C30	Phase 3	Up to 5 years
Proportion with clinically meaningful improvement in disease symptoms per EORTC QLQ-MY20	Phase 3	Up to 5 years
Proportion with clinically meaningful improvement in treatment side effects per EORTC QLQ-MY20	Phase 3	Up to 5 years
Proportion with clinically meaningful improvement in body image per EORTC QLQ-MY20	Phase 3	Up to 5 years
Proportion with clinically meaningful improvement in future perspective per EORTC QLQ-MY20	Phase 3	Up to 5 years
Proportion of clinically meaningful improvement in EQ-5D-5L VAS	Phase 3	Up to 5 years
Mean proportion of time with high side effect bother as measured by Functional Assessment of Cancer Therapy (FACIT)- Item Global Population 5 (GP5)	Phase 3 FACIT-Item GP5 will be used to assess the patient-reported impact of treatment toxicity that uses a single item "I am bothered by side effects of treatment" on a 5-point scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much).	Up to 5 years
Proportion of patients with high side effect bother as measured by FACIT- Item GP5	Phase 3	Up to 5 years
Occurrence of Anti-Drug Antibody (ADA) to linvoseltamab in serum	Phase 3	Up to 5 years
Magnitude of ADA to linvoseltamab in serum	Phase 3	Up to 5 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): June 5, 2026
• Primary Completion (Estimated): May 21, 2038
• Study Completion (Estimated): May 21, 2038

Study Registration Dates

• First Submitted: February 3, 2026
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Autologous Stem Cell Transplantation (ASCT); High-dose chemotherapy; Linvoseltamab; Newly Diagnosed Multiple Myeloma (NDMM); Transplant-Eligible; Bortezomib (V); Lenalidomide (R); Daratumumab (D), bortezomib (V), lenalidomide (R), dexamethasone (d) (DVRd)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Polycyclic Compounds; Piperidines; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Sulfonic Acids; Sulfur Acids; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Benzenesulfonates; Arylsulfonates; Arylsulfonic Acids; Lenalidomide; Bortezomib; Dexamethasone; Calcium Dobesilate; daratumumab
• Other Study ID Numbers: R5458-HM-2504; 2025-524032-19-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing 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

• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No