Multiple Myeloma
Conditions
Keywords
Newly Diagnosed Multiple Myeloma (NDMM), Autologous Stem Cell Transplantation (ASCT), Cluster of Differentiation 3 (CD3), BCMA, High Dose chemoTherapy (HDT), International Myeloma Working Group (IMWG)
Brief summary
This study is researching an experimental drug called linvoseltamab (called "study drug"). The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are eligible for high dose chemotherapy with autologous stem cell transplantation (transplant-eligible) or ineligible for autologous stem cell transplantation (transplant-ineligible). The aim of this clinical trial is to study the safety, tolerability (how the body reacts to the drug), and effectiveness (tumor shrinkage) of linvoseltamab in study participants with NDMM as a first step in determining if the study drug has a role in the treatment of NDMM. This study consists of 2 phases: * In Phase 1 Parts A and B, the study drug will be given to participants to study the side effects of the study drug and to establish the regimen (initial doses and full dose) of the study drug to be given to participants in Phase 2. * In Phase 1 Part C, the study drug will be given to participants to study the side effects when using different initial doses of the study drug. * In Phase 2, the study drug will be given to more participants to continue to assess the side effects of the study drug and to evaluate the activity of the study drug to shrink the tumor (multiple myeloma) in participants with NDMM. The study is looking at several research questions, including: * What side effects may happen from taking linvoseltamab? * What the right dosing regimen is for linvoseltamab? * How many participants treated with linvoseltamab have improvement of their disease and for how long? * The effects of linvoseltamab study treatment before and after transplant * How much linvoseltamab is in the blood at different times? * Whether the body makes antibodies against linvoseltamab (which could make the drug less effective or could lead to side effects).
Interventions
DRUGLinvoseltamab
Linvoseltamab will be administered by intravenous (IV) infusion
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Note: Phase 1 part B will be randomized 1:1. All other participants will be non-randomized.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 2. Confirmed diagnosis of symptomatic Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnosis criteria, as described in the protocol 3. Response-evaluable myeloma, according to the 2016 IMWG response criteria, as defined in the protocol 4. No prior therapy for MM, with the exception of prior emergent or palliative radiation and up to 1 month of single-agent corticosteroids, with washout periods as per the protocol 5. Participants must have evidence of adequate bone marrow reserves and hepatic, renal and cardiac function as defined in the protocol 6. Participants must be age \<70 and have adequate hepatic, renal, pulmonary and cardiac function to be considered transplant-eligible. The specific thresholds for adequate organ function are as per institutional guidance. Key
Exclusion criteria
1. Receiving any concurrent investigational agent with known or suspected activity against MM, or agents targeting the A proliferation-inducing ligand (APRIL)/ Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)/BCMA axis 2. Known Central Nervous System (CNS) involvement with MM, known or suspected Progressive Multifocal Leukoencephalopathy (PML), a history of neurocognitive conditions, or CNS movement disorder, or history of seizure within 12 months prior to study enrollment 3. Rapidly progressive symptomatic disease, (e.g. progressing renal failure or hypercalcemia not responsive to standard medical interventions), in urgent need of treatment with chemotherapy 4. Diagnosis of non-secretory MM, active plasma cell leukemia primary light-chain (AL) amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or known POEMS syndrome (Plasma cell dyscrasia with polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes) Note: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severity of TEAEs | Post-Last Linvoseltamab Dose, up to 90 days | Phase 1 |
| Incidence of Adverse Events of Special Interest (AESIs) | Post-Last Linvoseltamab Dose, up to 90 days | Phase 1 |
| Severity of AESIs | Post-Last Linvoseltamab Dose, up to 90 days | Phase 1 |
| Proportion of participants with a Very Good Partial Response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria | Up to 5 years | Phase 2 |
| Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy | Up to 5 years | Phase 2 Transplant-eligible cohort |
| Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy | Up to 5 years | Phase 2 Transplant-eligible cohort |
| Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II | Up to 5 years | Phase 2 Transplant-ineligible cohort |
| Proportion of participants achieving MRD-negative status as their best response after treatment period I without continuing to treatment period II | Up to 5 years | Phase 2 Transplant ineligible cohort |
| Incidence of Dose-Limiting Toxicities (DLTs) | End of the Observation period; up to day 28 | Phase 1 |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | Post-Last Linvoseltamab Dose, up to 90 days | Phase 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to platelet engraftment | Up to 100 days post-transplant | Phase 2 Transplant-eligible cohort |
| PFS after ASCT followed by 3 cycles of linvoseltamab | Up to 5 years | Phase 2 Transplant-eligible cohort |
| PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| ORR of participants deemed transplant-eligible and transplant-ineligible by the treating physician | Up to 5 years | Phase 2 |
| MRD-negative status of participants deemed transplant-eligible and transplant-ineligible by the treating physician | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| DOR of participants deemed transplant-eligible and transplant-ineligible by the treating physician | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| Concentrations of Linvoseltamab in serum | Post-Last Linvoseltamab Dose, up to 12 weeks | Phases 1 and 2 |
| Concentrations of total soluble B-Cell Maturation Antigen (BCMA) | Post-Last Linvoseltamab Dose, up to 12 weeks | Phases 1 and 2 |
| Incidence of Anti-Drug Antibodies (ADAs) to Linvoseltamab | Post-Last Linvoseltamab Dose, up to 30 days | Phases 1 and 2 |
| Magnitude of ADAs to Linvoseltamab | Post-Last Linvoseltamab Dose, up to 30 days | Phases 1 and 2 |
| Objective Response Rate (ORR) measured using the IMWG criteria | Up to 5 years | Phase 1 |
| Duration Of Response (DOR) measured using the IMWG criteria | Post-Last Linvoseltamab Dose, up to 90 days | Phase 1 |
| Progression-Free Survival (PFS) measured using the IMWG criteria | Post-Last Linvoseltamab Dose, up to 90 days | Phase 1 |
| Proportion of participants achieving MRD-negative status (at 10^-5) in participants with NDMM measured using the IMWG criteria | Post-Last Linvoseltamab Dose, up to 90 days | Phase 1 |
| Incidence of TEAEs | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| Severity of TEAEs | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| Incidence of AESIs | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| Overall Survival (OS) of participants deemed transplant-eligible and transplant-ineligible by the treating physician | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| Severity of AESIs | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| Time To Response (TTR) as measured using the IMWG criteria | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| ORR by risk levels | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| MRD-negative status by risk levels | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| DOR by risk levels | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| TTR by risk levels | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| PFS by risk levels | Post-Last Linvoseltamab Dose, up to 90 days | Phase 2 |
| Incidence of MRD-negative status | Up to 5 years | Phase 2 |
| Cluster of Differentiation 34+ (CD34+) stem cell yield | At cycle 4 of induction (each cycle is 28 days long) | Phase 2 Transplant-eligible cohort |
| Time to neutrophil engraftment | Up to 100 days post-transplant | Phase 2 Transplant-eligible cohort |
Countries
France, Spain, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed