A Proof-of-Concept Trial to Study the Safety and Activity of Linvoseltamab in Adult Participants With Smoldering Multiple Myeloma at High Risk of Developing Multiple Myeloma

NCT05955508 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: R5458-ONC-22562023-503524-11-00
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 17

Brief Summary

This study is researching an investigational drug called linvoseltamab ("study drug") in participants at high risk of developing Multiple Myeloma (MM), a group commonly labeled as High-Risk Smoldering Multiple Myeloma (HR-SMM). The aim of the study is to understand the safety and tolerability (how the body reacts to linvoseltamab) as well as the effectiveness (how well linvoseltamab eliminates plasma cells and prevents the development of MM) of the study drug. There are 2 parts to the study.

• In Part 1, linvoseltamab will be given to a small number of participants to study the early side effects (safety) of the study drug and make sure the treatment is acceptable.
• In Part 2, linvoseltamab will be given to more participants to further assess the side effects of the study drug and to evaluate the ability of linvoseltamab to treat HR-SMM and prevent progression to MM. The study is looking at several other research questions, including:
• How many participants treated with linvoseltamab (study drug) have improvement of their HR-SMM?
• 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 linvoseltamab less effective or could lead to side effects)

Conditions

Smoldering Multiple Myeloma (SMM)

Keywords

Linvoseltamab; Multiple Myeloma (MM); B cell Maturation Antigen (BCMA); Bispecific antibody

Outcome Measures

Primary Outcomes (6)

• Frequency of Adverse Events of Special Interest (AESI) during the safety run-in observation period

  AESI include grade 2 or higher Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS)

  Up to 35 days

• Frequency of Treatment-Emergent Adverse Events (TEAEs) during the safety run-in observation period

  Up to 35 days

• Severity of TEAEs during the safety run-in observation period

  Up to 35 days

• Complete Response (CR) as determined by the investigator

  Up to 7 years

• Minimal Residual Disease (MRD) negativity

  At 12 months

• MRD negativity

  At 24 months

Secondary Outcomes (18)

• Frequency of TEAEs during expansion part

  Up to 7 years

• Severity of TEAEs during expansion part

  Up to 7 years

• Frequency of Serious Adverse Events (SAEs)

  Up to 7 years

• Severity of SAEs

  Up to 7 years

• Frequency of laboratory abnormalities

  Up to 7 years

Study Arms (2)

Safety Run-In (Part 1)

EXPERIMENTAL

Drug: Linvoseltamab

Expansion (Part 2)

EXPERIMENTAL

Drug: Linvoseltamab

Interventions

Linvoseltamab DRUG

Administered per the protocol

Also known as: REGN5458, Lynozyfic™

Expansion (Part 2); Safety Run-In (Part 1)

Eligibility Criteria

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

You may qualify if:

• High-risk SMM diagnosis within 5 years of study enrollment, as described in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Adequate hematologic and hepatic function, as described in the protocol
• Estimated glomerular filtration rate ≥30 mL/min/1.73 m\^2

You may not qualify if:

• Evidence of myeloma defining events \*SLiM CRAB, as described in the protocol
• \*SLiM (greater than or equal to Sixty percent clonal plasma cells in the bone marrow, involved/uninvolved free Light chain ratio of ≥100 with the involved free light chain (FLC) being ≥100 mg/L, MRI with \>1 focal lesion) CRAB (hyperCalcemia, Renal insufficiency, Anemia, or lytic Bone lesions)
• Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), soft tissue plasmacytoma, or symptomatic multiple myeloma
• Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
• Any infection requiring hospitalization or treatment with intravenous anti-infectives within 28 days of first dose of study drug
• Uncontrolled Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection, as described in the protocol
• History of severe allergic reaction attributed to compounds with a similar chemical or biologic composition as the study drug or excipient

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (17)

Hospital Clinico Universitario Santiago de Compostela

Santiago de Compostela, A Coruna, 15706, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, Andalusia, 18014, Spain

Location

Hospital Universitari Son Llatzer

Palma Mallorca, Balearic Islands, 07198, Spain

Location

Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Quiron Salud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Clinico Universitario Virgen De La Arrixaca

El Palmar, Murcia, 30120, Spain

Location

Clinica Universidad de Navarra - Pamplona

Pamplona, Navarre, 31008, Spain

Location

University Hospital of Cabuenes

Gijón, Principality of Asturias, 33203, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Institut Catala d'Oncologia

Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Maranon (HGUGM) - Instituto de Investigacion Sanitaria Gregorio Maranon

Madrid, 28009, Spain

Location

Clinica Universidad de Navarra - Madrid

Madrid, 28027, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

University Hospital Doctor Peset

Valencia, 46017, Spain

Location

La Fe University Hospital

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Smoldering Multiple Myeloma; Multiple Myeloma

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2023
• First Posted: July 21, 2023
• Study Start: January 30, 2024
• Primary Completion (Estimated): January 25, 2033
• Study Completion (Estimated): January 25, 2033
• Last Updated: April 13, 2026

Record last verified: 2026-04

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

Locations

ES (17)