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Recurrent Multiple MyelomaPhase 1/2NCT07181941

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

A Phase 1/2 study testing Linvoseltamab, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Multiple Myeloma and Refractory Multiple Myeloma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Linvoseltamab, Bone Marrow Aspiration and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
24 Mar 2026to 30 Jun 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Madhav Dhodapkar, MBBS contact

206-606-4888

mdhodapk@fredhutch.org

United States1 site, 1 recruiting

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    Madhav Dhodapkar, MBBS, 206-606-4888, mdhodapk@fredhutch.org

    Madhav Dhodapkar, MBBS

    Recruiting

Other trials in United States

About this study

Official title: Pharmacodynamically Monitored Linvoseltamab Dosing De-Escalation in Relapsed Multiple Myeloma

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.

Read the detailed description

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 achieve VGPR or better after a minimum of 14 weeks of therapy and at least 10 full doses 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.

Being tested
Linvoseltamab, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Positron Emission Tomography
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LinvoseltamabBiological

    Also called Anti-BCMA x Anti-CD3 Bispecific Antibody REGN5458, Anti-BCMA/CD3 Bispecific Antibody REGN5458, BCMA x CD3 Bispecific Antibody REGN5458, Linvoseltamab-gcpt

    Given IV

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT or PET/CT

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood samples

Study groups in NCT07181941
Study groupRoleWhat they receive
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.
Receives: Biological: Linvoseltamab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Biospecimen Collection
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.
Receives: Biological: Linvoseltamab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Biospecimen Collection
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.
Receives: Biological: Linvoseltamab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Biospecimen Collection
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.
Receives: Biological: Linvoseltamab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Biospecimen Collection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of subjects who experience early disease progression

    Measured: Within 3 months of initiation of dosing de-escalation

Secondary outcomes (1)

  1. Measurable residual disease (MRD) negativity

    MRD negativity will be assessed at 10e^-6.

    Measured: One year after treatment initiation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2025
  2. Study start24 Mar 2026
  3. Primary completion30 Jun 2028 (estimated)
  4. Study completion30 Jun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07181941
Sponsor's protocol ID
RG1125714
Other IDs
NCI-2025-06211, FHIRB0020980
Status last verified
Sep 2026
First submitted
12 Sep 2025
Last updated
16 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Linvoseltamab, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Multiple Myeloma and Refractory Multiple Myeloma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Madhav Dhodapkar, MBBS (206-606-4888, mdhodapk@fredhutch.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of subjects who experience early disease progression (time frame: Within 3 months of initiation of dosing de-escalation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07181941.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.

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