This study involves people with two conditions that may lead to a type of blood cancer called multiple myeloma. The first condition is High-Risk Monoclonal Gammopathy of Undetermined Significance, which means the body is producing abnormal proteins that could develop into cancer. The second condition is Non-High-Risk Smoldering Multiple Myeloma, where abnormal plasma cells are present in the bone marrow but have not yet caused symptoms or damage. The study will use a medication called Linvoseltamab, also known by its code name REGN5458, which is given through an infusion into a vein. Additional medications may be used to manage side effects, including diphenhydramine hydrochloride (an antihistamine taken by mouth), tocilizumab (given through an infusion), dexamethasone (a corticosteroid that can be taken by mouth or given through an infusion), and paracetamol (a pain and fever reliever taken by mouth).
The purpose of this study is to find out if Linvoseltamab can eliminate the abnormal plasma cells that might turn into multiple myeloma and to determine the safest and most effective dose to use. The study will also look at how well people tolerate the medication and whether it causes any unwanted effects. In the first part of the study, different dose levels of Linvoseltamab will be tested in small groups to identify the highest dose that can be given safely. In the second part, a larger group of people will receive the selected dose to see how well it works at causing a complete response, which means the abnormal cells can no longer be detected.
During the study, participants will receive Linvoseltamab through infusions over a period of up to 27 months. Doctors will monitor participants closely for any side effects and will check blood samples to see if the treatment is working. The study will measure whether participants achieve a complete response, meaning all signs of the abnormal cells have disappeared, and whether this response lasts over time. Other measurements will include checking for minimal residual disease, which looks for very small amounts of abnormal cells that may still be present, and tracking how long people remain free from the disease getting worse. Blood tests will also be done to measure the amount of Linvoseltamab in the body and to check if the body develops antibodies against the medication.
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