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

Regeneron Pharmaceuticals

Status and phase: Begins enrollment in 1 month; Phase 3; Phase 2

Conditions: Multiple Myeloma (MM)

Treatments: Drug: Lenalidomide; Drug: Linvoseltamab; Drug: Bortezomib; Drug: Daratumumab; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT07428369

2025-524032-19-00 (EU Trial (CTIS) Number)

R5458-HM-2504

Details and patient eligibility

About

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)

Enrollment: 1,570 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,570 participants in 3 patient groups

Linvo-VR with ASCT

Experimental group

Treatment:

Drug: Bortezomib

Drug: Linvoseltamab

Drug: Lenalidomide

Linvo-VR without ASCT

Experimental group

Treatment:

Drug: Bortezomib

Drug: Linvoseltamab

Drug: Lenalidomide

DVRd with ASCT

Active Comparator group

Treatment:

Drug: Dexamethasone

Drug: Daratumumab

Drug: Bortezomib

Drug: Lenalidomide