Response-Based Dose Reduction of Linvoseltamab in the Treatment of Relapsed, Refractory, or Triple-Class Relapsed/Refractory Multiple Myeloma

NCT ID: NCT07181941

Last Updated: 2026-01-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-03-01

Study Completion Date

2028-06-30

Brief Summary

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This phase I/II trial evaluates the safety and feasibility of early, response-based dose reduction of linvoseltamab in the treatment of patients multiple myeloma that has come back after a period of improvement (relapsed), that does not respond to treatment (refractory), or that is resistant to three classes of therapeutic agents, including proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies (triple-class relapsed/refractory). Linvoseltamab is a bispecific antibody. Upon administration, linvoseltamab binds to the BCMA protein on cancer cells and the CD3 protein on T cells (a type of immune cell). This generates an immune response that stimulates the T cells to kill the cancer cells. Optimal dosing schedules of linvoseltamab have not yet been determined. Reducing the dosage of linvoseltamab may reduce treatment-related side effects while maintaining long-term disease outcomes.

Detailed Description

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OUTLINE:

STEP-UP DOSING: Patients receive linvoseltamab intravenously (IV) over 30-240 minutes once a week (QW) in weeks 1-14 and then once every 2 weeks (Q2W) thereafter in the absence of disease progression or unacceptable toxicity. Patients are evaluated for disease response starting at week 3 and continuing every 4 weeks. Patients without very good partial response (VGPR) or better continue receiving linvoseltamab IV over 30-240 minutes Q2W in the absence of disease progression or unacceptable toxicity. Patients who do achieve VGPR or better after a minimum of 14 weeks of therapy are then assigned to 1 of 3 dose de-escalation cohorts. Patients undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial. Patients may undergo computed tomography (CT) or positron emission tomography (PET)/CT throughout the trial if indicated.

COHORT 1: Patients receive linvoseltamab IV over 30-240 minutes once every 4 weeks (Q4W) in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial. Patients may undergo CT or PET/CT throughout the trial if indicated.

COHORT 2: Patients receive linvoseltamab IV over 30-240 minutes once every 8 weeks (Q8W) in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial. Patients may undergo CT or PET/CT throughout the trial if indicated.

COHORT 3: Patients receive linvoseltamab IV over 30-240 minutes once every 12 weeks (Q12W) in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial. Patients may undergo CT or PET/CT throughout the trial if indicated.

After completion of study treatment, patients are followed up for 3 months.

Conditions

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Recurrent Multiple Myeloma Refractory Multiple Myeloma Triple-Class Refractory Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Step-up dosing (linvoseltamab)

Patients receive linvoseltamab IV over 30-240 minutes QW in weeks 1-14 and then Q2W thereafter in the absence of disease progression or unacceptable toxicity. Patients are evaluated for disease response starting at week 3 and continuing every 4 weeks. Patients without VGPR or better continue receiving linvoseltamab IV over 30-240 minutes Q2W in the absence of disease progression or unacceptable toxicity. Patients who do achieve VGPR or better after a minimum of 14 weeks of therapy are then assigned to 1 of 3 dose de-escalation cohorts. Patients undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial. Patients may undergo CT or PET/CT throughout the trial if indicated.

Group Type EXPERIMENTAL

Linvoseltamab

Intervention Type BIOLOGICAL

Given IV

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Computed Tomography

Intervention Type PROCEDURE

Undergo CT or PET/CT

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Cohort 1 (Q4W linvoseltamab)

Patients receive linvoseltamab IV over 30-240 minutes Q4W in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial. Patients may undergo CT or PET/CT throughout the trial if indicated.

Group Type EXPERIMENTAL

Linvoseltamab

Intervention Type BIOLOGICAL

Given IV

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Computed Tomography

Intervention Type PROCEDURE

Undergo CT or PET/CT

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Cohort 2 (Q8W linvoseltamab)

Patients receive linvoseltamab IV over 30-240 minutes Q8W in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial. Patients may undergo CT or PET/CT throughout the trial if indicated.

Group Type EXPERIMENTAL

Linvoseltamab

Intervention Type BIOLOGICAL

Given IV

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Computed Tomography

Intervention Type PROCEDURE

Undergo CT or PET/CT

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Cohort 3 (Q12W linvoseltamab)

Patients receive linvoseltamab IV over 30-240 minutes Q12W in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial. Patients may undergo CT or PET/CT throughout the trial if indicated.

Group Type EXPERIMENTAL

Linvoseltamab

Intervention Type BIOLOGICAL

Given IV

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Computed Tomography

Intervention Type PROCEDURE

Undergo CT or PET/CT

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Interventions

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Linvoseltamab

Given IV

Intervention Type BIOLOGICAL

Bone Marrow Aspiration

Undergo bone marrow aspiration

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

Intervention Type PROCEDURE

Computed Tomography

Undergo CT or PET/CT

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

Intervention Type PROCEDURE

Other Intervention Names

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Anti-BCMA x Anti-CD3 Bispecific Antibody REGN5458 Anti-BCMA/CD3 Bispecific Antibody REGN5458 BCMA x CD3 Bispecific Antibody REGN5458 Linvoseltamab-gcpt Lynozyfic REGN 5458 REGN-5458 REGN5458 Biopsy of Bone Marrow Biopsy, Bone Marrow CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Biological Sample Collection Biospecimen Collected Specimen Collection

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years. Myeloma is not seen in the younger age group and safety of B-cell maturation antigen (BCMA) T-cell engagers (TCE) in this group is not known
* Ability to understand and willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of potential study participants
* Confirmed diagnosis of active multiple myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria
* Patients must have myeloma that is measurable and response evaluable according to 2016 IMWG response criteria. Measurable disease is defined as one of the following, documented ≤ 14 days prior to registration:

* Serum M protein ≥ 1 g/dl
* Urine M protein ≥ 200 mg/24h
* Free light chain (FLC) assay with involved FLC ≥ 10 mg/dl and abnormal FLC ratio
* A patient with immunoglobulin A (IgA) MM without measurable M protein may be enrolled if quantitative (quant) IgA level ≥ 400 mg/dl and can be followed longitudinally
* Plasmacytoma target lesion defined as measurable based on at least 1 soft tissue lesion ≥ 2 cm in long axis on CT or PET/CT, if not previously irradiated
* Skin lesions ≥ 2 cm in long axis as measured with a ruler
* Patients with relapsed or refractory myeloma who have received at least 4 prior lines of therapy including proteasome inhibitor (PI), immunomodulatory imide drug (IMiD), and anti-CD38 monoclonal antibody
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
* Adequate organ function (based on testing ≤14 days prior to registration):

* Adequate hematologic function before dosing as measured by:

* Platelet count ≥50 x 10⁹/L. A patient may not have received a platelet transfusion ≤7 days in order to meet this platelet eligibility requirement
* Absolute neutrophil count (ANC) ≥1.0 x 10⁹/L. A patient may not have received granulocyte colony stimulating factor (G-CSF) ≤2 days in order to meet this absolute neutrophil count eligibility requirement
* Hemoglobin ≥8.0 g/dL
* Adequate renal and hepatic function, defined as:

* Total bilirubin ≤1.5 x ULN
* Transaminase (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\]) ≤2.5 x ULN
* Alkaline phosphatase ≤2.5 x ULN

* Patients with Gilbert syndrome do not need to meet this total bilirubin requirement provided that the total bilirubin is unchanged from the baseline value
* Serum creatinine clearance by Cockcroft-Gault ≥30 mL/min. A patient with a creatinine clearance by Cockcroft-Gault who does not meet eligibility criteria may be considered for enrollment per principal investigator discretion if a measured creatinine clearance (based on 24-hour urine collection or other reliable method) is ≥30 mL/min
* Prior treatment with BCMA-targeted antibody-drug conjugates (ADCs) is allowable if all adverse events (AEs) attributable to these therapies have resolved to grade 1 or lower
* Willing and able to comply with clinic visits and study-related procedures and provide informed consent signed by study patient

Exclusion Criteria

* Diagnosis of known plasma cell leukemia, known primary systemic light-chain amyloidosis (excluding myeloma-associated amyloidosis), known Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or known POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
* Patients with known MM brain lesions or meningeal involvement
* History of known neurodegenerative condition, central nervous system (CNS) movement disorder, or patients with a history of seizure within 12 months prior to study enrollment
* Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or anti-inflammatory equivalent within 72 hours of start of study drug
* Live or live attenuated vaccines with replicating potential within 28 days prior to first study drug administration
* Previous treatment with chimeric antigen receptor (CAR) T therapy or any gene therapy products
* Any infection requiring hospitalization or treatment with intravenous (IV) anti-infectives within 2 weeks of first administration of study drug
* Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV)
* Known allergy or hypersensitivity to components of linvoseltamab (REGN5458)
* Women of childbearing potential (WOCBP) with a positive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test are ineligible for this study

* WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Post-menopausal state is defined as no menses for 12 months without an alternate medical cause
* Participants who are receiving other investigational agents
* Women of childbearing potential (WCOBP) and men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose
* Uncontrolled or concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Another malignancy in the past 5 years, except for non-melanoma skin cancer that has undergone potentially curative therapy or in situ cancer, or any other tumor that has been deemed to be effectively treated with definitive local control and with curative intent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Madhav Dhodapkar, MBBS

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

Central Contacts

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Madhav Dhodapkar, MBBS

Role: CONTACT

206-606-4888

Facility Contacts

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Madhav Dhodapkar, MBBS

Role: primary

206-606-4888

Other Identifiers

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NCI-2025-06211

Identifier Type: REGISTRY

Identifier Source: secondary_id

RG1125714

Identifier Type: -

Identifier Source: org_study_id

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