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

NCT07393282 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: R5458-HM-241452025-523252-31-00
• Study Type: interventional
• Target: 270
• Locations: 0 countries
• Sites: N/A

Brief Summary

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)

Conditions

High Risk Smoldering Multiple Myeloma (HR-SMM)

Keywords

Linvoseltamab; Multiple Myeloma (MM); B Cell Maturation Antigen (BCMA); Bispecific antibody; Smoldering Multiple Myeloma (SMM); Smoldering Myeloma; HR-SMM; Linozyfic; Darzalex

Outcome Measures

Primary Outcomes (2)

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

  Up to 5 years

• Biochemical PFS per IMWG criteria

  Up to 5 years

Secondary Outcomes (24)

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

  Up to 3 years

• Time to death

  Up to 9 years

• Achievement of Overall Response Rate (ORR) of Partial Response or better (≥PR) per IMWG criteria

  Up to 3 years

• Best Overall Response (BOR) per IMWG criteria

  Up to 3 years

• Achievement of MRD-negativity

  Up to 3 years

Study Arms (2)

Linvoseltamab

EXPERIMENTAL

Drug: Linvoseltamab

Daratumumab

ACTIVE COMPARATOR

Drug: Daratumumab

Interventions

Linvoseltamab DRUG

Administered per the protocol

Also known as: REGN5458, Lynozyfic™

Linvoseltamab

Daratumumab DRUG

Administered per the protocol

Also known as: Darzalex Faspro®, Darzalex®

Daratumumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

MeSH Terms

Conditions

Multiple Myeloma; Smoldering Multiple Myeloma

Interventions

daratumumab

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; Precancerous Conditions; Hypergammaglobulinemia

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2026
• First Posted: February 6, 2026
• Study Start: March 25, 2026
• Primary Completion (Estimated): July 22, 2033
• Study Completion (Estimated): July 22, 2033
• Last Updated: March 16, 2026

Record last verified: 2026-03

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