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

Purpose

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)

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. HR-MGUS or NHR-SMM as defined in the protocol 2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 3. Adequate hematologic and hepatic function, as described in the protocol 4. Estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73 m^2 by the Modification of Diet in Renal Disease (MDRD) equation

Exclusion Criteria

  1. High-risk SMM, as defined in the protocol 2. Evidence of any of myeloma-defining events, as described in the protocol 3. Diagnosis of systemic light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), solitary plasmacytoma, or symptomatic MM 4. Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol 5. Any infection requiring hospitalization or treatment with intravenous (IV) anti-infectives within 28 days of the first dose of linvoseltamab 6. 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 NOTE: Other protocol defined inclusion/exclusion criteria apply

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Safety Run-In (Part 1)
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
    Administered per the protocol
    Other names:
    • REGN5458
    • Lynozyfic™
Experimental
Expansion (Part 2) - Dose regimen 1
Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens
  • Drug: Linvoseltamab
    Administered per the protocol
    Other names:
    • REGN5458
    • Lynozyfic™
Experimental
Expansion (Part 2) - Dose regimen 2
Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens
  • Drug: Linvoseltamab
    Administered per the protocol
    Other names:
    • REGN5458
    • Lynozyfic™
Experimental
Expansion (Part 2) - Dose regimen 3
Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens
  • Drug: Linvoseltamab
    Administered per the protocol
    Other names:
    • REGN5458
    • Lynozyfic™
Experimental
Expansion (Part 2) - Dose regimen 4
Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens
  • Drug: Linvoseltamab
    Administered per the protocol
    Other names:
    • REGN5458
    • Lynozyfic™

Recruiting Locations

Johns Hopkins Hospital
Baltimore, Maryland 21287

Dana-Farber Cancer Institute
Boston, Massachusetts 02215

University of Michigan Health
Ann Arbor, Michigan 48109

NYU Langone Health Perlmutter Cancer Center
New York, New York 10016

Stony Brook University Hospital
Stony Brook, New York 11794

Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107

University of Washington
Seattle, Washington 98109

More Details

Status
Recruiting
Sponsor
Regeneron Pharmaceuticals

Study Contact

Clinical Trials Administrator
844-734-6643
clinicaltrials@regeneron.com