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

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & 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 Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06140524
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Regeneron Pharmaceuticals
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Clinical Trial Management
Principal Investigator Affiliation	Regeneron Pharmaceuticals
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM)

Arms & Interventions

Arms

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.

Experimental: Expansion (Part 2) - Dose regimen 1

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

Experimental: Expansion (Part 2) - Dose regimen 2

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

Experimental: Expansion (Part 2) - Dose regimen 3

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

Experimental: Expansion (Part 2) - Dose regimen 4

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

Interventions

Drug: - Linvoseltamab

Administration by intravenous (IV) infusion

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Clinical Trials Administrator

clinicaltrials@regeneron.com

844-734-6643

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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