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 (LINKER-MGUS1)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Linvoseltamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06140524

2023-505242-25-00 (Other Identifier)

R5458-ONC-2257

Details and patient eligibility

About

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).

Enrollment: 116 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Key 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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116 participants in 5 patient groups

Safety Run-In (Part 1)

Experimental group

Description:

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.

Treatment:

Drug: Linvoseltamab

Expansion (Part 2) - Dose regimen 1

Experimental group

Description:

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

Treatment:

Drug: Linvoseltamab

Expansion (Part 2) - Dose regimen 2

Experimental group

Description:

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

Treatment:

Drug: Linvoseltamab

Expansion (Part 2) - Dose regimen 3

Experimental group

Description:

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

Treatment:

Drug: Linvoseltamab

Expansion (Part 2) - Dose regimen 4

Experimental group

Description:

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

Treatment:

Drug: Linvoseltamab