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 (LINKER-MM4)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Linvoseltamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05828511

R5458-ONC-2158

2022-500800-24-00 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 132 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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
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.

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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132 participants in 3 patient groups

Phase 1 cohort

Experimental group

Description:

Linvoseltamab dose escalation (part A) and dose expansion (part B) for participants with NDMM who are treatment-naïve.

Treatment:

Drug: Linvoseltamab

Phase 2 - transplant ineligible cohort

Experimental group

Description:

Transplant-ineligible participants, enrolled in dose expansion, will receive selected Linvoseltamab regimen until disease progression as per protocol.

Treatment:

Drug: Linvoseltamab

Phase 2 - transplant eligible cohort

Experimental group

Description:

Transplant-eligible participants, enrolled in dose expansion, will receive selected linvoseltamab regimen for a fixed duration of treatment as per protocol

Treatment:

Drug: Linvoseltamab