A Proof-of-Concept Study to Learn Whether Linvoseltamab Can Eliminate Abnormal Plasma Cells That May Lead to Multiple Myeloma in Adult Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma

NCT06140524 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: R5458-ONC-22572023-505242-25-00
• Study Type: interventional
• Target: 116
• Locations: 6 countries
• Sites: 20

Brief Summary

This study is researching an investigational drug called linvoseltamab ("study drug") in participants at moderate risk of developing multiple myeloma (about 3 to 10% average annual risk), a group that consists of patients with precancerous conditions called High-Risk Monoclonal Gammopathy of Undetermined Significance (HR-MGUS) and Non-High-Risk Smoldering Multiple Myeloma (NHR-SMM). The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of HR-MGUS and NHR-SMM. The study is looking at several other research questions, including:

• How many participants treated with linvoseltamab have improvement of their HR-MGUS or NHR-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 the drug less effective or could lead to side effects).

Conditions

Monoclonal Gammopathy of Undetermined Significance (MGUS); Smoldering Multiple Myeloma (SMM)

Keywords

linvoseltamab; monoclonal immunoglobulin (M-protein); cancer interception; immunotherapy; plasma cell disorders

Outcome Measures

Primary Outcomes (4)

• Frequency of Adverse Events Interest (AEI) during the safety observation period

  Part 1 An AEI is a toxicity potentially related to study treatment that may preclude dose escalation or expansion according to the Bayesian Optimal Interval (BOIN) design decision rules

  35 days

• Frequency of Treatment-Emergent Adverse Event (TEAEs) during the safety observation period

  Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)

  35 days

• Severity of TEAEs during the safety observation period

  Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)

  35 days

• Achievement of Complete Response (CR) as determined by the investigator

  Part 2

  Up to 5.5 years

Secondary Outcomes (14)

• Frequency of TEAEs

  Up to 5.5 years

• Severity of TEAEs

  Up to 5.5 years

• Frequency of Serious Adverse Events (SAEs)

  Up to 5.5 years

• Severity of SAEs

  Up to 5.5 years

• Frequency of laboratory abnormalities

  Up to 5.5 years

Study Arms (5)

Safety Run-In (Part 1)

EXPERIMENTAL

Sequential groups of participants will be enrolled to assess the initial safety and tolerability of the step-up regimen leading up to the start of different full doses of linvoseltamab.

Drug: Linvoseltamab

Expansion (Part 2) - Dose regimen 1

EXPERIMENTAL

Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens

Drug: Linvoseltamab

Expansion (Part 2) - Dose regimen 2

EXPERIMENTAL

Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens

Drug: Linvoseltamab

Expansion (Part 2) - Dose regimen 3

EXPERIMENTAL

Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens

Drug: Linvoseltamab

Expansion (Part 2) - Dose regimen 4

EXPERIMENTAL

Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens

Drug: Linvoseltamab

Interventions

Linvoseltamab DRUG

Administered per the protocol

Also known as: REGN5458, Lynozyfic™

Expansion (Part 2) - Dose regimen 1; Expansion (Part 2) - Dose regimen 2; Expansion (Part 2) - Dose regimen 3; Expansion (Part 2) - Dose regimen 4; 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:

• HR-MGUS or NHR-SMM as defined 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 (GFR) ≥30 mL/min/1.73 m\^2 by the Modification of Diet in Renal Disease (MDRD) equation

You may not qualify if:

• High-risk SMM, as defined in the protocol
• Evidence of any of myeloma-defining events, as described in the protocol
• Diagnosis of systemic light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), solitary plasmacytoma, or symptomatic MM
• 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 (IV) anti-infectives within 28 days of the first dose of linvoseltamab
• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (20)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan Health

Ann Arbor, Michigan, 48109, United States

RECRUITING

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

University of Washington

Seattle, Washington, 98109, United States

RECRUITING

Algemeen Ziekenhuis (AZ) Klina

Brasschaat, Antwerpen, 2930, Belgium

RECRUITING

Algemeen Ziekenhuis AZ Delta

Roeselare, West-Vlaanderen, 8800, Belgium

RECRUITING

Cork University Hospital

Cork, T12 EC8P, Ireland

RECRUITING

Istituto Romagnolo per lo Studio Dei Tumori Dino Amadori

Meldola, Forli-Cesena, 47014, Italy

RECRUITING

San Paolo Hospital

Milan, Lombardy, 20142, Italy

RECRUITING

Wojewodzki Szpital Zespolony - Ludwik Rydygier Provincial Hospital

Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

RECRUITING

Pratia MCM Krakow

Krakow, Malopolska, 30-510, Poland

RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, Andalusia, 18014, Spain

RECRUITING

Hospital Universitari Mutua Terrassa

Terrassa, Barcelona, 08221, Spain

RECRUITING

Hospital Clinico Universitario Virgen De La Arrixaca

El Palmar, Murcia, 30120, Spain

RECRUITING

Hospital de Cabuenes

Gijón, Principality of Asturias, 33203, Spain

RECRUITING

Hospital Sant Pau

Barcelona, 08041, Spain

RECRUITING

Universitaru Hospital La Princesa

Madrid, 28006, Spain

RECRUITING

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

RECRUITING

MeSH Terms

Conditions

Monoclonal Gammopathy of Undetermined Significance; Smoldering Multiple Myeloma

Condition Hierarchy (Ancestors)

Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Neoplasms

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2023
• First Posted: November 20, 2023
• Study Start: September 16, 2024
• Primary Completion (Estimated): May 18, 2032
• Study Completion (Estimated): May 18, 2032
• Last Updated: April 8, 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 (7); PL (2); BE (2); IE (1); US (6); IT (2)