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

The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of high-risk monoclonal gammopathy of undetermined significance (HR-MGUS) and non high-risk smoldering multiple myeloma (NHR-SMM). This requires understanding the safety and tolerability of the study drug (how the body reacts to linvoseltamab) as well as the effectiveness of the study drug (how well linvoseltamab eliminates plasma cells). All participants will start treatment with gradually increasing doses of linvoseltamab (step-up doses) before they start receiving the assigned full dose.

The study is split into 2 parts:

• In Part 1, separate groups of 3-6 patients will receive different full doses of linvoseltamab to evaluate the short-term side effects (safety) and tolerability of the study drug within the first 5 weeks after starting treatment. The data collected will help to make a decision about the dosing regimens chosen for Part 2.
• In Part 2, a larger number of participants will be randomized to different dosing regimens to further assess the side effects of linvoseltamab, and to evaluate the ability of linvoseltamab to eliminate abnormal plasma cells in 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: 104 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 m2 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 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

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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104 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