A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
- Registration Number
- NCT05828511
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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, 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 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 ability 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 132
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Confirmed diagnosis of symptomatic multiple myeloma (MM) by International Myeloma Working Group (IMWG) diagnosis criteria
- Measurable disease, according to the 2016 IMWG response criteria, as defined in the protocol
- 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
- Participants must have evidence of adequate bone marrow reserves and hepatic, renal and cardiac function as defined in the protocol
- 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
- 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
- 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
- Rapidly progressive symptomatic disease, (e.g. progressing renal failure or hypercalcemia not responsive to standard medical interventions), in urgent need of treatment with chemotherapy
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1 cohort Linvoseltamab Linvoseltamab dose escalation (part A) and dose expansion (part B) for participants with NDMM who are treatment-naïve. Phase 2 - transplant ineligible cohort Linvoseltamab Transplant-ineligible participants, enrolled in dose expansion, will receive selected Linvoseltamab regimen until disease progression as per protocol. Phase 2 - transplant eligible cohort Linvoseltamab Transplant-eligible participants, enrolled in dose expansion, will receive selected linvoseltamab regimen for a fixed duration of treatment as per protocol
- Primary Outcome Measures
Name Time Method Severity of AESIs Post-Last Linvoseltamab Dose, up to 90 days Phase 1
Incidence of dose-limiting toxicities (DLTs) End of the Observation period; up to day 28 Phase 1
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
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 MRD-negative status (at 10^-5) after induction without consolidation therapy Up to 5 years Phase 2 Transplant-eligible cohort
Incidence of treatment-emergent adverse events (TEAEs) Post-Last Linvoseltamab Dose, up to 90 days Phase 1
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 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 as their best response after treatment period I without continuing to treatment period II Up to 5 years Phase 2 Transplant ineligible cohort
- Secondary Outcome Measures
Name Time Method Objective response rate (ORR) measured using the IMWG criteria Up to 5 years Phase 1
Concentrations of total soluble B-cell maturation antigen (BCMA) Post-Last Linvoseltamab Dose, up to 12 weeks Phases 1 and 2
Duration of Response (DOR) 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
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
PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician Post-Last Linvoseltamab Dose, up to 90 days Phase 2
Progression-free survival (PFS) measured using the IMWG criteria Post-Last Linvoseltamab Dose, up to 90 days Phase 1
Incidence of AESIs Post-Last Linvoseltamab Dose, up to 90 days Phase 2
PFS by risk levels Post-Last Linvoseltamab Dose, up to 90 days 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
Incidence of anti-drug antibodies (ADAs) to Linvoseltamab Post-Last Linvoseltamab Dose, up to 30 days Phases 1 and 2
ORR by risk levels Post-Last Linvoseltamab Dose, up to 90 days Phase 2
Titer of ADAs to Linvoseltamab Post-Last Linvoseltamab Dose, up to 30 days Phases 1 and 2
Severity of TEAEs 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
Concentrations of Linvoseltamab in serum Post-Last Linvoseltamab Dose, up to 12 weeks Phases 1 and 2
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
Severity of AESIs 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
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
Time to response (TTR) as measured using the IMWG criteria Post-Last Linvoseltamab Dose, up to 90 days Phase 2
MRD-negative rstatus 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
Incidence of MRD-negative status Up to 5 years Phase 2
Time to neutrophil engraftment Up to 100 days post-transplant Phase 2 Transplant-eligible cohort
Time to platelet engraftment Up to 100 days post-transplant Phase 2 Transplant-eligible cohort
TTR by risk levels Post-Last Linvoseltamab Dose, up to 90 days Phase 2
PFS after ASCT followed by 3 cycles of linvoseltamab Up to 5 years Phase 2 Transplant-eligible cohort
Trial Locations
- Locations (30)
Centre Hospitalier Universitaire (CHU) Montpellier
🇫🇷Montpellier, France
Hopital Saint Louis
🇫🇷Paris, France
Hopital Pitié Salpetriere APHP
🇫🇷Paris, France
Institut Catala dOncologia (ICO Hospitalet)
🇪🇸Barcelona, Spain
University of California Los Angeles (UCLA)
🇺🇸Los Angeles, California, United States
UC Irvine Health
🇺🇸Orange, California, United States
Colorado Blood Cancer Institute/SCRI
🇺🇸Denver, Colorado, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Perlmutter Cancer Center at NYU Langone Hospital - Long Island
🇺🇸Mineola, New York, United States
Perlmutter Cancer Center
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Gustave Roussy
🇫🇷Villejuif, Ile De France, France
Hopital Necker
🇫🇷Paris, Ile-de-France, France
Centre Hospitalier Universitaire (CHU) de Poitiers
🇫🇷Poitiers, Nouvelle-Aquitaine, France
CHU De Lille
🇫🇷Lille, France
Hospital Universitario Central De Asturias
🇪🇸Oviedo, Asturias, Spain
Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital General Universitario Doctor Balmis Alicante
🇪🇸Alicante, Comunidad Valenciana, Spain
Hospital Universitario Quiron Salud Madrid
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Universitary Hospital La Princesa
🇪🇸Madrid, Spain
Clinica Universidad de Navarra - Madrid
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
La Fe University Hospital
🇪🇸Valencia, Spain