RecruitingInterventionalPhase 1/Phase 2

Phase 1/2 Study of Linvoseltamab (Anti-BCMA X Anti-CD3 Bispecific Antibody) in Previously Untreated Patients With Symptomatic Multiple Myeloma

NCT ID: NCT05828511Sponsor: Regeneron PharmaceuticalsLast updated: 2026-05-13

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).

Arms & interventions

DrugLinvoseltamab
Linvoseltamab will be administered by intravenous (IV) infusion

Outcome measures

Primary

Incidence of Dose-Limiting Toxicities (DLTs)
Phase 1
Time frame: End of the Observation period; up to day 28
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Phase 1
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Severity of TEAEs
Phase 1
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Incidence of Adverse Events of Special Interest (AESIs)
Phase 1
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Severity of AESIs
Phase 1
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Proportion of participants with a Very Good Partial Response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria
Phase 2
Time frame: Up to 5 years
Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy
Phase 2 Transplant-eligible cohort
Time frame: Up to 5 years
Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy
Phase 2 Transplant-eligible cohort
Time frame: Up to 5 years
Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II
Phase 2 Transplant-ineligible cohort
Time frame: Up to 5 years
Proportion of participants achieving MRD-negative status as their best response after treatment period I without continuing to treatment period II
Phase 2 Transplant ineligible cohort
Time frame: Up to 5 years

Secondary

Concentrations of Linvoseltamab in serum
Time frame: Post-Last Linvoseltamab Dose, up to 12 weeks
Concentrations of total soluble B-Cell Maturation Antigen (BCMA)
Time frame: Post-Last Linvoseltamab Dose, up to 12 weeks
Incidence of Anti-Drug Antibodies (ADAs) to Linvoseltamab
Time frame: Post-Last Linvoseltamab Dose, up to 30 days
Magnitude of ADAs to Linvoseltamab
Time frame: Post-Last Linvoseltamab Dose, up to 30 days
Objective Response Rate (ORR) measured using the IMWG criteria
Time frame: Up to 5 years
Duration Of Response (DOR) measured using the IMWG criteria
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Progression-Free Survival (PFS) measured using the IMWG criteria
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Proportion of participants achieving MRD-negative status (at 10^-5) in participants with NDMM measured using the IMWG criteria
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Incidence of TEAEs
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Severity of TEAEs
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Incidence of AESIs
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Severity of AESIs
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
ORR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Time frame: Up to 5 years
MRD-negative status of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
DOR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Overall Survival (OS) of participants deemed transplant-eligible and transplant-ineligible by the treating physician
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Time To Response (TTR) as measured using the IMWG criteria
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
ORR by risk levels
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
MRD-negative status by risk levels
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
DOR by risk levels
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
TTR by risk levels
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
PFS by risk levels
Time frame: Post-Last Linvoseltamab Dose, up to 90 days
Incidence of MRD-negative status
Time frame: Up to 5 years
Cluster of Differentiation 34+ (CD34+) stem cell yield
Time frame: At cycle 4 of induction (each cycle is 28 days long)
Time to neutrophil engraftment
Time frame: Up to 100 days post-transplant
Time to platelet engraftment
Time frame: Up to 100 days post-transplant
PFS after ASCT followed by 3 cycles of linvoseltamab
Time frame: Up to 5 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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/Exclusion criteria apply

Study locations (13)

University of California Los Angeles (UCLA)

Los Angeles, California, 90095

Recruiting

UC Irvine Health

Orange, California, 92868

Recruiting

Colorado Blood Cancer Institute/SCRI

Denver, Colorado, 80218

Recruiting

Norton Cancer Institute

Louisville, Kentucky, 40207

Recruiting

Karmanos Cancer Institute

Detroit, Michigan, 48201

Recruiting

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901

Recruiting

Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Mineola, New York, 11501

Recruiting

Perlmutter Cancer Center

New York, New York, 10016

Recruiting

Columbia University _ New York Presbyterian

New York, New York, 10032

Recruiting

Stony Brook University Hospital

Stony Brook, New York, 11794

Recruiting

Levine Cancer Institute

Charlotte, North Carolina, 28204

Recruiting

Duke University Health System (DUHS)

Durham, North Carolina, 27705

Recruiting

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting