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NCT Number: NCT07393282

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

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)

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Key information

Conditions

High Risk Smoldering Multiple Myeloma (HR-SMM) Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Hypergammaglobulinemia Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Multiple Myeloma Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Precancerous Conditions Smoldering Multiple Myeloma Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Emory University - Winship Cancer Institute, Atlanta, Georgia, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

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

Key Exclusion Criteria:

  • Evidence of myeloma-defining events attributable to the underlying plasma cell dyscrasia, as defined in the protocol
  • Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), plasma cell leukemia, or soft tissue plasmacytoma
  • History of neurodegenerative condition, progressive multifocal leukoencephalopathy, or Central Nervous System (CNS) movement disorder
  • History of a seizure within the 12 months of randomization
  • 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

Treatment and study plan

Linvoseltamab

Drug

Administered per the protocol

Other names: REGN5458, Lynozyfic™

Daratumumab

Drug

Administered per the protocol

Other names: Darzalex Faspro®, Darzalex®

Primary outcomes

  1. Clinical Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) criteria

    Time frame: Up to 5 years

  2. Biochemical PFS per IMWG criteria

    Time frame: Up to 5 years

Secondary outcomes

  1. Achievement of Minimal Residual Disease (MRD) Complete Response (CR) at 10^-5 per IMWG criteria

    Time frame: Up to 3 years

  2. Time to death

    Time frame: Up to 9 years

  3. Overall Response Rate (ORR) of Partial Response or better (≥PR) per IMWG criteria

    Time frame: Up to 3 years

  4. Best Overall Response (BOR) per IMWG criteria

    Time frame: Up to 3 years

  5. Achievement of MRD-negativity

    Time frame: Up to 3 years

  6. Sustained MRD-negativity

    Time frame: Up to 3 years

  7. Duration of MRD-negative CR

    Time frame: Up to 3 years

  8. Duration Of Response (DOR) per IMWG criteria

    Time frame: Up to 5 years

  9. Occurrence of Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Up to 3 years

  10. Severity of TEAEs

    Time frame: Up to 3 years

  11. Occurrence of Serious Adverse Events (SAEs)

    Time frame: Up to 3 years

  12. Change from baseline score in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) scale

    Time frame: Up to 5 years

    The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported QoL using 1 GHS/QoL scale, 5 functioning scales (physical, role, emotional, cognitive and social) and 9 symptom scales / items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer.

    For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 5 = "excellent" with higher scores indicating better functioning and positive changes from baseline indicate improvement.

  13. Change from baseline score in EORTC QLQ-C30 physical functioning scale

    Time frame: Up to 5 years

  14. Change from baseline score in EORTC QLQ-C30 role functioning scale

    Time frame: Up to 5 years

  15. Change from baseline score in EORTC QLQ-C30 emotional functioning scale

    Time frame: Up to 5 years

  16. Change from baseline score in EORTC QLQ-C30 pain scale

    Time frame: Up to 5 years

    The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported QoL using 1 GHS/QoL scale, 5 functioning scales (physical, role, emotional, cognitive and social) and 9 symptom scales / items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer.

    For the 9 symptom scales, scores range from 1 = "not at all" to 9 = "very much" higher scores indicate higher symptom burden and negative changes from baseline indicate improvement.

  17. Change from baseline score in EORTC QLQ-C30 fatigue scale

    Time frame: Up to 5 years

  18. Change from baseline score in EORTC IL478 future perspectives scale

    Time frame: Up to 5 years

    EORTC IL478 corresponds to the EORTC QLQ-Multiple Myeloma Module 20 (MY20) future Perspective Scale. This is a is a self-administered instrument to assess QoL in persons with MM.

    For the future perspective 3 items are analyzed.

    A high score for an item represents a high level of symptomatic problem.

  19. Change from baseline score in EuroQoL-5 Dimensions 5-Level Questionnaire Visual Analogue Scale (EQ-5D-5L VAS )

    Time frame: Up to 5 years

    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".

  20. Functional Assessment of Cancer Therapy (FACIT)- Item Global Population 5 (GP5) responses

    Time frame: Up to 5 years

    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).

  21. Change from baseline in FACIT- Item GP5 score

    Time frame: Up to 5 years

  22. Concentrations of linvoseltamab in serum

    Time frame: Up to 5 years

  23. Occurrence of Anti-Drug Antibodies (ADAs) to linvoseltamab in serum

    Time frame: Up to 5 years

  24. Magnitude of ADA to linvoseltamab in serum

    Time frame: Up to 5 years

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials Administrator

CONTACT

[email protected]

844-734-6643

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study title

A Phase 3, Randomized, Open-Label Study of Linvoseltamab Versus Daratumumab in Participants With Smoldering Multiple Myeloma at High Risk of Developing Multiple Myeloma

Acronym: LINKER-SMM2

Important dates

Study start
2026
Primary completion
2033
Study completion
2033
First posted
Feb 6, 2026
Registry last updated
Jul 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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