Smoldering Multiple Myeloma (SMM)
Conditions
Keywords
Linvoseltamab, Multiple Myeloma (MM), B cell Maturation Antigen (BCMA), Bispecific antibody
Brief summary
This study is researching an investigational drug called linvoseltamab ("study drug") in participants at high risk of developing Multiple Myeloma (MM), a group commonly labeled as High-Risk Smoldering Multiple Myeloma (HR-SMM). The aim of the study is to understand the safety and tolerability (how the body reacts to linvoseltamab) as well as the effectiveness (how well linvoseltamab eliminates plasma cells and prevents the development of MM) of the study drug. There are 2 parts to the study. * In Part 1, linvoseltamab will be given to a small number of participants to study the early side effects (safety) of the study drug and make sure the treatment is acceptable. * In Part 2, linvoseltamab will be given to more participants to further assess the side effects of the study drug and to evaluate the ability of linvoseltamab to treat HR-SMM and prevent progression to MM. The study is looking at several other research questions, including: * How many participants treated with linvoseltamab (study drug) have improvement of their HR-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 linvoseltamab less effective or could lead to side effects)
Interventions
DRUGLinvoseltamab
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
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. High-risk SMM diagnosis within 5 years of study enrollment, as described 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 ≥30 mL/min/1.73 m\^2 Key
Exclusion criteria
1. Evidence of myeloma defining events \*SLiM CRAB, as described in the protocol \*SLiM (greater than or equal to Sixty percent clonal plasma cells in the bone marrow, involved/uninvolved free Light chain ratio of ≥100 with the involved free light chain (FLC) being ≥100 mg/L, MRI with \>1 focal lesion) CRAB (hyperCalcemia, Renal insufficiency, Anemia, or lytic Bone lesions) 2. Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), soft tissue plasmacytoma, or symptomatic multiple myeloma 3. Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol 4. Any infection requiring hospitalization or treatment with intravenous anti-infectives within 28 days of first dose of study drug 5. 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 6. History of severe allergic reaction attributed to compounds with a similar chemical or biologic composition as the study drug or excipient NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Events of Special Interest (AESI) during the safety run-in observation period | Up to 35 days | AESI include grade 2 or higher Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) |
| Frequency of Treatment-Emergent Adverse Events (TEAEs) during the safety run-in observation period | Up to 35 days | — |
| Severity of TEAEs during the safety run-in observation period | Up to 35 days | — |
| Complete Response (CR) as determined by the investigator | Up to 7 years | — |
| Minimal Residual Disease (MRD) negativity | At 12 months | — |
| MRD negativity | At 24 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of TEAEs during expansion part | Up to 7 years | As assessed by the NCI-CTCAE grading system version 5 (for all grades) |
| Severity of TEAEs during expansion part | Up to 7 years | As assessed by the NCI-CTCAE grading system version 5 (for all grades) |
| Frequency of Serious Adverse Events (SAEs) | Up to 7 years | — |
| Severity of SAEs | Up to 7 years | — |
| Frequency of laboratory abnormalities | Up to 7 years | — |
| Severity of laboratory abnormalities | Up to 7 years | — |
| Overall response of Partial Response (PR) or better | Up to 7 years | — |
| Duration Of Response (DOR) | Up to 7 years | — |
| Biochemical Progression-Free-Survival (PFS) | Up to 7 years | — |
| MRD negativity among participants that achieve Very Good Partial Response (VGPR) or better | Up to 3 years after end of treatment | — |
| Sustained MRD negativity | Up to 3 years after end of treatment | — |
| Time from treatment initiation to date of any myeloma-defining event | Up to 7 years | — |
| Time from start of treatment to date of progression to MM or death | Up to 7 years | — |
| Time to initiation of first-line treatment for MM | Up to 7 years | — |
| Overall Survival (OS) | Up to 7 years | — |
| Concentration of linvoseltamab in serum | Up to 2 years | — |
| Incidence of Anti-Drug Antibodies (ADAs) to linvoseltamab | Up to 2 years | — |
| Magnitude of ADAs to linvoseltamab | Up to 2 years | — |
Countries
Spain
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed