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
Purpose
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).
Condition
- Multiple Myeloma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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 3. Measurable disease, 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.
Exclusion Criteria
- 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 Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Note: Phase 1 part B will be randomized 1:1. All other participants will be non-randomized.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Phase 1 cohort |
Linvoseltamab dose escalation (part A) and dose expansion (part B) for participants with NDMM who are treatment-naïve. |
|
|
Experimental Phase 2 - transplant ineligible cohort |
Transplant-ineligible participants, enrolled in dose expansion, will receive selected Linvoseltamab regimen until disease progression as per protocol. |
|
|
Experimental Phase 2 - transplant eligible cohort |
Transplant-eligible participants, enrolled in dose expansion, will receive selected linvoseltamab regimen for a fixed duration of treatment as per protocol |
|
Recruiting Locations
Los Angeles 5368361, California 5332921 90095
Orange 5379513, California 5332921 92868
Denver 5419384, Colorado 5417618 80218
Louisville 4299276, Kentucky 6254925 40207
Detroit 4990729, Michigan 5001836 48201
New Brunswick 5101717, New Jersey 5101760 08901
Mineola 5127134, New York 5128638 11501
New York 5128581, New York 5128638 10016
New York 5128581, New York 5128638 10032
Stony Brook 5139865, New York 5128638 11794
Charlotte 4460243, North Carolina 4482348 28204
Durham 4464368, North Carolina 4482348 27705
Houston 4699066, Texas 4736286 77030
More Details
- Status
- Recruiting
- Sponsor
- Regeneron Pharmaceuticals