The primary purpose of the study is to understand how well the study drug can eliminateabnormal plasma cells and laboratory signs of high-risk monoclonal gammopathy ofundetermined significance (HR-MGUS) and non high-risk smoldering multiple myeloma(NHR-SMM). This requires understanding the safety and tolerability of the study drug (howthe body reacts to linvoseltamab) as well as the effectiveness of the study drug (howwell linvoseltamab eliminates plasma cells). All participants will start treatment withgradually increasing doses of linvoseltamab (step-up doses) before they start receivingthe 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).
Not Provided
Drug: Linvoseltamab
Administration by intravenous (IV) infusion
Other Name: REGN5458
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
Johns Hopkins Hospital
Baltimore, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Stony Brook University Hospital
Stony Brook, New York, United States
University of Washington
Seattle, Washington, United States
Hospital Universitario Virgen de las Nieves
Granada, Andalusia, Spain
Hospital de Cabuenes
Gijon, Asturias, Spain
Hospital Universitari Mutua Terrassa
Terrassa, Barcelona, Spain
Hospital Clinico Universitario Virgen De La Arrixaca
El Palmar, Murcia, Spain
Hospital Sant Pau
Barcelona, Spain
Universitaru Hospital La Princesa
Madrid, Spain
Hospital General Universitario Morales Meseguer
Murcia, Spain
Clinical Trials Administrator
844-734-6643
clinicaltrials@regeneron.com
Clinical Trial Management, Study Director
Regeneron Pharmaceuticals