Relapsed and/or Refractory Multiple Myeloma (RRMM)
Conditions
Keywords
BCMA X CD3 Bispecific Monoclonal Antibody, Bispecific combination therapy, Linvoseltamab, Carfilzomib, Proteasome inhibitor
Brief summary
This study is researching a drug called linvoseltamab (also called "study drug") either given alone or in combination with another anti-myeloma drug called carfilzomib, compared to several standard treatments for progressive Multiple Myeloma (MM) after at least 1 but no more than 3 prior therapies. The aim of this study is to see if the safety and efficacy of linvoseltamab alone or in combination with carfilzomib can deliver better outcomes (deeper and longer responses that help extend life) than standard treatment options. 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
DRUGCarfilzomib
Administered per the protocol
DRUGDaratumumab
Administered per the protocol
DRUGDexamethasone
Administered per the protocol
DRUGPomalidomide
Administered per the protocol
DRUGBortezomib
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. Participant with RRMM who received at least 1 but not more than 3 prior lines of therapy, which must have included treatment with lenalidomide and either a Protease Inhibitor (PI) or anti-CD38 monoclonal antibody 2. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2 3. Confirmed progressive disease according to IMWG criteria during or after the most recent line of therapy Key
Exclusion criteria
1. Prior treatment with a T cell-based immunotherapy targeting BCMA, including BCMA-directed bispecific antibodies, Bispecific T-cell Engagers (BiTEs), and Chimeric Antigen Receptor (CAR) T cells. Antibody-drug conjugates targeting BCMA (eg, belantamab mafodotin) are not excluded 2. Diagnosis of plasma cell leukemia, symptomatic amyloidosis (including myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 3. Known Central Nervous System (CNS) involvement of myeloma including meningeal involvement 4. History of neurodegenerative condition, Progressive Multifocal Leukoencephalopathy (PML), or CNS movement disorder NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Treatment Emergent Adverse Events (TEAEs) | Up to 5 years | Part 1 |
| Severity of TEAEs | Up to 5 years | Part 1 |
| Occurrence of Adverse Events of Special Interest (AESI) | Up to 5 years | Part 1 |
| Severity of AESIs | Up to 5 years | Part 1 |
| Occurrence of Serious Adverse Events (SAEs) | Up to 5 years | Part 1 |
| Severity of SAEs | Up to 5 years | Part 1 |
| Minimal Residual Disease (MRD)-negative Complete Response (CR) | At 12 months | Part 2 |
| Progression-Free Survival (PFS) per IMWG response criteria as determined by BIRC | Up to 5 years | Part 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of grade ≥2 Cytokine Release Syndrome (CRS) | Up to 28 days | Part 1 |
| Timing of grade ≥2 CRS | Up to 28 days | Part 1 |
| Overall Survival (OS) | Up to 7 years | Part 2 |
| Achievement of Partial Response (PR) or better per IMWG response criteria as determined by BIRC | Up to 5 years | Part 2 |
| Achievement of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by BIRC | Up to 5 years | Part 2 |
| Achievement of CR or better per IMWG response criteria as determined by BIRC | Up to 5 years | Part 2 |
| Duration Of Response (DOR) as per IMWG response criteria | Up to 5 years | Part 2 |
| Time To Progression (TTP) as per IMWG response criteria | Up to 5 years | Part 2 |
| Time To Next Treatment (TTNT) | Up to 5 years | Part 2 |
| Second PFS | Up to 5 years | Part 2 |
| MRD-negative CR criteria at any time | Up to 5 years | Part 2 |
| Time to PR IMWG response category | Up to 5 years | Part 2 |
| Time to VGPR IMWG response category | Up to 5 years | Part 2 |
| Time to CR IMWG response category | Up to 5 years | Part 2 |
| Time to stringent Complete Response (sCR) IMWG response category | Up to 5 years | Part 2 |
| Sustained MRD-negative CR | Up to 5 years | Part 2 |
| Duration of MRD-negative CR | Up to 5 years | Part 2 |
| Occurrence of TEAEs | Up to 5 years | Part 2 |
| Severity of TEAEs | Up to 5 years | Part 2 |
| Occurrence of AESIs | Up to 5 years | Part 2 |
| Severity of AESIs | Up to 5 years | Part 2 |
| Occurrence of SAEs | Up to 5 years | Part 2 |
| Severity of SAEs | Up to 5 years | Part 2 |
| Concentrations of linvoseltamab in serum over time | Up to 5 years | Part 2 |
| Incidence of Antidrug Antibodies (ADAs) to linvoseltamab | Up to 5 years | Part 2 |
| Magnitude of ADAs to linvoseltamab | Up to 5 years | Part 2 |
| Concentrations total soluble B-cell Maturation Antigen (sBCMA) in serum over time | Up to 5 years | Part 2 |
| Change from baseline in Global Health Status (GHS)/Quality of Life (QoL), per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Up to 5 years | Part 2 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. Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much." |
| Change from baseline in Physical Functioning (PF), per EORTC QLQ-C30 | Up to 5 years | Part 2 |
| Change from baseline in Role Functioning (RF), per EORTC QLQ-C30 | Up to 5 years | Part 2 |
| Change from baseline in pain, per EORTC QLQ-C30 | Up to 5 years | Part 2 |
| Change from baseline in fatigue, per EORTC QLQ-C30 | Up to 5 years | Part 2 |
| Change in patient reported Disease Symptoms (DS) per EORTC Quality of Life Questionnaire-Multiple Myeloma (MM) module 20 [QLQ-MY20]) | Up to 5 years | Part 2 EORTC QLQ-MY20 is an accompanying 20-item validated questionnaire that measure quality of life among patients living with MM across 4 scales (disease symptoms, side effect of treatment, body image and future perspective). A high score represents a high level of symptoms or problems. |
| Change in patient reported Treatment Side Effects (TSE) per EORTC QLQ-MY20 | Up to 5 years | Part 2 |
| Change in patient-reported health state per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L]) Visual Analogue Scale (VAS) | Up to 5 years | Part 2 The EQ-5D-5L is a generic questionnaire that measures HRQoL across 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) across 5 levels (no problems, slight problems, some problems, severe problems and extreme problems) and a VAS of pain (where 0: no pain and 10: worst pain), higher scores indicate higher pain. |
| Change in patient-reported overall impact of treatment per Functional Assessment of Chronic Illness Therapy (FACIT) item GP5 | Up to 5 years | Part 2 FACIT Item GP5 is a recommended item by the Federal Drug Administration (FDA) in its recent draft guidance for cancer trials to assess patient-reported overall impact of treatment toxicity. It 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) |
Countries
Australia, South Korea, Taiwan, United Kingdom, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed