High Risk Smoldering Multiple Myeloma (HR-SMM)
Conditions
Keywords
Linvoseltamab, Multiple Myeloma (MM), B Cell Maturation Antigen (BCMA), Bispecific antibody, Smoldering Multiple Myeloma (SMM), Smoldering Myeloma, HR-SMM, Linozyfic, Darzalex
Brief summary
This study is researching an experimental drug called linvoseltamab (also called "study drug") compared to another drug called daratumumab, in participants with Smoldering Multiple Myeloma (SMM), who are at a High Risk (HR) of developing active multiple myeloma. The aim of this study is to find out whether linvoseltamab is better than daratumumab in delaying the development of MM. The study is looking at several other research questions, including: * 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
DRUGDaratumumab
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Eastern Cooperative Oncology Group performance status score ≤1 2. SMM diagnosis per IMWG criteria as defined in the protocol 3. Meets HR-SMM criteria by 1 of the risk models as defined in the protocol Key
Exclusion criteria
1. Evidence of myeloma-defining events attributable to the underlying plasma cell dyscrasia, as defined in the protocol 2. Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), plasma cell leukemia, or soft tissue plasmacytoma 3. History of neurodegenerative condition, progressive multifocal leukoencephalopathy, or Central Nervous System (CNS) movement disorder 4. History of a seizure within the 12 months of randomization 5. Prior exposure to any approved or investigational treatments directed against a clonal plasma cell disorder (including but not limited to conventional chemotherapies, radiotherapy, immunomodulatory drugs, proteasome inhibitors, anti-CD38 antibodies). Ongoing treatment with other monoclonal antibodies (eg, infliximab, rituximab) or other treatments likely to interfere with study procedures or results, as described in the protocol. NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) criteria | Up to 5 years |
| Biochemical PFS per IMWG criteria | Up to 5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of Minimal Residual Disease (MRD) Complete Response (CR) at 10^-5 per IMWG criteria | Up to 3 years | — |
| Time to death | Up to 9 years | — |
| Overall Response Rate (ORR) of Partial Response or better (≥PR) per IMWG criteria | Up to 3 years | — |
| Best Overall Response (BOR) per IMWG criteria | Up to 3 years | — |
| Achievement of MRD-negativity | Up to 3 years | — |
| Sustained MRD-negativity | Up to 3 years | — |
| Duration of MRD-negative CR | Up to 3 years | — |
| Duration Of Response (DOR) per IMWG criteria | Up to 5 years | — |
| Occurrence of Treatment-Emergent Adverse Events (TEAEs) | Up to 3 years | — |
| Severity of TEAEs | Up to 3 years | — |
| Occurrence of Serious Adverse Events (SAEs) | Up to 3 years | — |
| Change from baseline score in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) scale | Up to 5 years | The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported QoL using 1 GHS/QoL scale, 5 functioning scales (physical, role, emotional, cognitive and social) and 9 symptom scales / items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer. For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 5 = "excellent" with higher scores indicating better functioning and positive changes from baseline indicate improvement. |
| Change from baseline score in EORTC QLQ-C30 physical functioning scale | Up to 5 years | — |
| Change from baseline score in EORTC QLQ-C30 role functioning scale | Up to 5 years | — |
| Change from baseline score in EORTC QLQ-C30 emotional functioning scale | Up to 5 years | — |
| Change from baseline score in EORTC QLQ-C30 pain scale | Up to 5 years | The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported QoL using 1 GHS/QoL scale, 5 functioning scales (physical, role, emotional, cognitive and social) and 9 symptom scales / items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer. For the 9 symptom scales, scores range from 1 = "not at all" to 9 = "very much" higher scores indicate higher symptom burden and negative changes from baseline indicate improvement. |
| Change from baseline score in EORTC QLQ-C30 fatigue scale | Up to 5 years | — |
| Change from baseline score in EORTC IL478 future perspectives scale | Up to 5 years | EORTC IL478 corresponds to the EORTC QLQ-Multiple Myeloma Module 20 (MY20) future Perspective Scale. This is a is a self-administered instrument to assess QoL in persons with MM. For the future perspective 3 items are analyzed. A high score for an item represents a high level of symptomatic problem. |
| Change from baseline score in EuroQoL-5 Dimensions 5-Level Questionnaire Visual Analogue Scale (EQ-5D-5L VAS ) | Up to 5 years | The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: "no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems". The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labeled "Best imaginable health state" and "Worst imaginable health state". |
| Functional Assessment of Cancer Therapy (FACIT)- Item Global Population 5 (GP5) responses | Up to 5 years | FACIT-Item GP5 will be used to assess the patient-reported impact of treatment toxicity that uses a single item "I am bothered by side effects of treatment" on a 5-point scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much). |
| Change from baseline in FACIT- Item GP5 score | Up to 5 years | — |
| Concentrations of linvoseltamab in serum | Up to 5 years | — |
| Occurrence of Anti-Drug Antibodies (ADAs) to linvoseltamab in serum | Up to 5 years | — |
| Magnitude of ADA to linvoseltamab in serum | Up to 5 years | — |
Countries
Japan, South Korea, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed