A Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM) (LINKER-SMM2)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: High Risk Smoldering Multiple Myeloma (HR-SMM)

Treatments: Drug: Linvoseltamab; Drug: Daratumumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT07393282

R5458-HM-24145

2025-523252-31-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

This study is researching an experimental drug called linvoseltamab (also called "study drug") compared to another drug called daratumumab, in participants with Smoldering Multiple Myeloma (SMM), who are at a High Risk (HR) of developing active multiple myeloma.

The aim of this study is to find out whether linvoseltamab is better than daratumumab in delaying the development of MM.

The study is looking at several other research questions, including:

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

Enrollment: 270 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Eastern Cooperative Oncology Group performance status score ≤1
2. SMM diagnosis per IMWG criteria as defined in the protocol
3. Meets HR-SMM criteria by 1 of the risk models as defined in the protocol

Key Exclusion Criteria:

1. Evidence of myeloma-defining events attributable to the underlying plasma cell dyscrasia, as defined in the protocol
2. Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), plasma cell leukemia, or soft tissue plasmacytoma
3. History of neurodegenerative condition, progressive multifocal leukoencephalopathy, or Central Nervous System (CNS) movement disorder
4. History of a seizure within the 12 months of randomization
5. Prior exposure to any approved or investigational treatments directed against a clonal plasma cell disorder (including but not limited to conventional chemotherapies, radiotherapy, immunomodulatory drugs, proteasome inhibitors, anti-CD38 antibodies). Ongoing treatment with other monoclonal antibodies (eg, infliximab, rituximab) or other treatments likely to interfere with study procedures or results, as described 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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270 participants in 2 patient groups

Linvoseltamab

Experimental group

Treatment:

Drug: Linvoseltamab

Daratumumab

Active Comparator group

Treatment:

Drug: Daratumumab