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NCT Number: NCT06140524

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

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).

Recruiting

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

AZ St.-Elisabeth Herentals vzw, Herentals, Antwerp, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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

NOTE: Other protocol defined inclusion/exclusion criteria apply

Treatment and study plan

Linvoseltamab

Drug

Administered per the protocol

Other names: REGN5458, Lynozyfic™

Primary outcomes

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

    Time frame: 35 days

    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

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

    Time frame: 35 days

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

  3. Severity of TEAEs during the safety observation period

    Time frame: 35 days

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

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

    Time frame: Up to 5.5 years

    Part 2

Secondary outcomes

  1. Frequency of TEAEs

    Time frame: Up to 5.5 years

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

  2. Severity of TEAEs

    Time frame: Up to 5.5 years

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

  3. Frequency of Serious Adverse Events (SAEs)

    Time frame: Up to 5.5 years

  4. Severity of SAEs

    Time frame: Up to 5.5 years

  5. Frequency of laboratory abnormalities

    Time frame: Up to 5.5 years

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

  6. Severity of laboratory abnormalities

    Time frame: Up to 5.5 years

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

  7. Minimal Residual Disease (MRD) negativity among participants that achieve a response of CR

    Time frame: Up to 5.5 years

  8. Sustained MRD negativity on an annual basis

    Time frame: Up to 3 years after achievement of CR

  9. Overall response of Partial Response (PR) or better as determined by the investigator

    Time frame: Up to 5.5 years

  10. Duration Of Response (DOR) as determined by the investigator

    Time frame: Up to 5.5 years

  11. Biochemical Progression-Free Survival (PFS) as determined by the investigator

    Time frame: Up to 5.5 years

  12. Concentration of linvoseltamab in serum over time

    Time frame: Up to 9 months

  13. Incidence of Anti-Drug Antibodies (ADAs) to linvoseltamab over the study duration

    Time frame: Up to 5.5. years

  14. Magnitude of ADAs to linvoseltamab over the study duration

    Time frame: Up to 5.5. 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

Phase 2 Dose-Ranging and Interception Study of Linvoseltamab in Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma

Acronym: LINKER-MGUS1

Important dates

Study start
2024
Primary completion
2032
Study completion
2032
First posted
Nov 20, 2023
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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