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
- Conditions
- Monoclonal Gammopathy of Undetermined Significance (MGUS)Smoldering Multiple Myeloma (SMM)
- Interventions
- Registration Number
- NCT06140524
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 104
- HR-MGUS or NHR-SMM as defined in the protocol
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Adequate hematologic and hepatic function, as described in the protocol
- Estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 by the modification of diet in renal disease (MDRD) equation
Key
- High-risk SMM, as defined in the protocol
- Evidence of any of myeloma-defining events, as described in the protocol
- Diagnosis of systemic light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), solitary plasmacytoma, or symptomatic MM
- Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
- Any infection requiring hospitalization or treatment with IV anti-infectives within 28 days of the first dose of linvoseltamab
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Expansion (Part 2) - Dose regimen 1 Linvoseltamab Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens Safety Run-In (Part 1) Linvoseltamab 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. Expansion (Part 2) - Dose regimen 2 Linvoseltamab Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens Expansion (Part 2) - Dose regimen 3 Linvoseltamab Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens Expansion (Part 2) - Dose regimen 4 Linvoseltamab Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens
- Primary Outcome Measures
Name Time Method Frequency of adverse events of special interest (AESI) during the safety observation period 35 days Part 1 As assessed by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system version 5 (for all grades). AESI include grade 2 or higher cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), grade 3 or higher tumor lysis syndrome (TLS), infusion-related reaction (IRR), allergic reactions, infections and hepatitis B virus (HBV) reactivation
Frequency of treatment-emergent adverse event (TEAEs) during the safety observation period 35 days Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Severity of TEAEs during the safety observation period 35 days Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Achievement of complete response (CR) as determined by the investigator Up to 5.5 years Part 2
- Secondary Outcome Measures
Name Time Method Concentration of linvoseltamab in serum over time Up to 9 months Frequency of serious adverse events (SAEs) Up to 5.5 years Frequency of laboratory abnormalities Up to 5.5 years As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Frequency of TEAEs Up to 5.5 years As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Overall response of partial response (PR) or better as determined by the investigator Up to 5.5 years Duration of response (DOR) as determined by the investigator Up to 5.5 years Biochemical progression-free survival (PFS) as determined by the investigator Up to 5.5 years Severity of TEAEs Up to 5.5 years As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Severity of laboratory abnormalities Up to 5.5 years As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Minimal residual disease (MRD) negativity among participants that achieve a response of CR Up to 5.5 years Sustained MRD negativity on an annual basis Up to 3 years after achievement of CR Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time Up to 9 months Titer of ADAs to linvoseltamab over time Up to 9 months Severity of SAEs Up to 5.5 years
Trial Locations
- Locations (11)
Universitaru Hospital La Princesa
🇪🇸Madrid, Spain
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 Universitari Mutua Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital Clinico Universitario Virgen De La Arrixaca
🇪🇸El Palmar, Murcia, Spain
Hospital de Cabuenes
🇪🇸Gijon, Asturias, Spain
Hospital Sant Pau
🇪🇸Barcelona, Spain
Hospital General Universitario Morales Meseguer
🇪🇸Murcia, Spain