Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM)
Conditions
Keywords
linvoseltamab, monoclonal immunoglobulin (M-protein), cancer interception, immunotherapy, plasma cell disorders
Brief summary
This study is researching an investigational drug called linvoseltamab ("study drug") in participants at moderate risk of developing multiple myeloma (about 3 to 10% average annual risk), a group that consists of patients with precancerous conditions called High-Risk Monoclonal Gammopathy of Undetermined Significance (HR-MGUS) and Non-High-Risk Smoldering Multiple Myeloma (NHR-SMM). The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of 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).
Interventions
DRUGLinvoseltamab
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 m\^2 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 intravenous (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, as described in the protocol NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Events Interest (AEI) during the safety observation period | 35 days | Part 1 An AEI is a toxicity potentially related to study treatment that may preclude dose escalation or expansion according to the Bayesian Optimal Interval (BOIN) design decision rules |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Frequency of TEAEs | Up to 5.5 years | As assessed by the NCI-CTCAE grading system version 5 (for all grades) |
| Severity of TEAEs | Up to 5.5 years | As assessed by the NCI-CTCAE grading system version 5 (for all grades) |
| Frequency of Serious Adverse Events (SAEs) | Up to 5.5 years | — |
| Severity of 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) |
| 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 | — |
| 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 | — |
| Concentration of linvoseltamab in serum over time | Up to 9 months | — |
| Incidence of Anti-Drug Antibodies (ADAs) to linvoseltamab over the study duration | Up to 5.5. years | — |
| Magnitude of ADAs to linvoseltamab over the study duration | Up to 5.5. years | — |
Countries
Belgium, France, Ireland, Italy, Poland, Spain, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed