Response-Based Dose Reduction of Linvoseltamab in the Treatment of Relapsed, Refractory, or Triple-Class Relapsed/Refractory Multiple Myeloma
Pharmacodynamically Monitored Linvoseltamab Dosing De-Escalation in Relapsed Multiple Myeloma
3 other identifiers
interventional
30
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Mar 2026
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 12, 2025
CompletedFirst Posted
Study publicly available on registry
September 19, 2025
CompletedStudy Start
First participant enrolled
March 24, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2028
March 27, 2026
March 1, 2026
2.3 years
September 12, 2025
March 24, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Number of subjects who experience early disease progression
Within 3 months of initiation of dosing de-escalation
Secondary Outcomes (1)
Measurable residual disease (MRD) negativity
One year after treatment initiation
Study Arms (4)
Step-up dosing (linvoseltamab)
EXPERIMENTALPatients 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.
Cohort 1 (Q4W linvoseltamab)
EXPERIMENTALPatients 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.
Cohort 2 (Q8W linvoseltamab)
EXPERIMENTALPatients 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.
Cohort 3 (Q12W linvoseltamab)
EXPERIMENTALPatients 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.
Interventions
Given IV
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo CT or PET/CT
Undergo PET/CT
Undergo collection of blood samples
Eligibility Criteria
You may qualify if:
- 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
- +10 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- Regeneron Pharmaceuticalscollaborator
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Madhav Dhodapkar, MBBS
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 12, 2025
First Posted
September 19, 2025
Study Start
March 24, 2026
Primary Completion (Estimated)
June 30, 2028
Study Completion (Estimated)
June 30, 2028
Last Updated
March 27, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share