- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05955508
A Proof-of-Concept Trial to Study the Safety and Activity of Linvoseltamab in Participants With Smoldering Multiple Myeloma at High Risk of Developing Multiple Myeloma
Phase 2 Study of Linvoseltamab in Patients With Smoldering Multiple Myeloma at High Risk of Progression to Multiple Myeloma
This study is researching an investigational drug called linvoseltamab ("study drug") in participants at high risk of developing multiple myeloma (MM), a group commonly labeled as high-risk smoldering multiple myeloma (HR-SMM).
The aim of the study is to understand the safety and tolerability (how your body reacts to linvoseltamab) as well as the effectiveness (how well linvoseltamab eliminates plasma cells and prevents the development of MM) of the study drug. There are 2 parts to the study.
- In Part 1, linvoseltamab will be given to a small number of participants to study the early side effects (safety) of the study drug and make sure the treatment is acceptable.
- In Part 2, linvoseltamab will be given to more participants to continue to assess the side effects of the study drug and to evaluate the ability of linvoseltamab to treat HR-SMM and prevent progression to MM.
The study is looking at several other research questions, including:
- How many participants treated with linvoseltamab (study drug) have improvement of their HR-SMM?
- What side effects may happen from taking the study drug?
- How much study drug is in your blood at different times?
- Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Clinical Trials Administrator
- Phone Number: 844-734-6643
- Email: clinicaltrials@regeneron.com
Study Locations
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Madrid, Spain, 28034
- Recruiting
- Hospital Universitario Ramón y Cajal
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Madrid, Spain, 28027
- Recruiting
- Clinica Universidad de Navarra - Madrid
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Salamanca, Spain, 37007
- Recruiting
- Hospital Universitario de Salamanca
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Valencia, Spain, 46017
- Recruiting
- University Hospital Doctor Peset
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Valencia, Spain, 46026
- Recruiting
- University Hospital La Fe
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Andalusia
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Granada, Andalusia, Spain, 18014
- Recruiting
- Hospital Universitario Virgen de las Nieves
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Asturias
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Gijon, Asturias, Spain, 33203
- Recruiting
- University Hospital of Cabuenes
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Baleares
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Palma Mallorca, Baleares, Spain, 07198
- Recruiting
- Hospital Universitari Son Llatzer
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Madrid
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Pozuelo de Alarcón, Madrid, Spain, 28223
- Recruiting
- Hospital Universitario Quiron Salud Madrid
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Navarra
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Pamplona, Navarra, Spain, 31008
- Recruiting
- Clinica Universidad de Navarra
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
KEY Inclusion Criteria:
- High-risk SMM diagnosis within 5 years of study enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Adequate hematologic and hepatic function, as described in the protocol
- Estimated glomerular filtration rate ≥30 mL/min/1.73 m^2
KEY Exclusion Criteria:
Evidence of myeloma defining events *SLiM CRAB, as described in the protocol
*SLiM (greater than or equal to Sixty percent clonal plasma cells in the bone marrow, involved/uninvolved free Light chain ratio of ≥100 with the involved free light chain (FLC) being ≥100 mg/L, MRI with >1 focal lesion) CRAB (hyperCalcemia, Renal insufficiency, Anemia, or lytic Bone lesions)
- Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), soft tissue plasmacytoma, or symptomatic multiple myeloma
- Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
- Any infection requiring hospitalization or treatment with IV anti-infectives within 28 days of first dose of study drug
- Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection
- History of severe allergic reaction attributed to compounds with a similar chemical or biologic composition as the study drug or excipient
NOTE: Other protocol defined inclusion/exclusion criteria apply
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Safety Run-In (Part 1)
Evaluation of initial safety and tolerability of the step-up regimen leading up to the start of full dose linvoseltamab.
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Administration by intravenous (IV) infusion
Other Names:
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Experimental: Expansion (Part 2)
Linvoseltamab monotherapy according to the same dosing schedule established in the safety run-in part.
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Administration by intravenous (IV) infusion
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Frequency of adverse events of special interest (AESI) during the safety run-in observation period
Time Frame: Up to 35 days
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AESI include grade 2 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)
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Up to 35 days
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Frequency of treatment-emergent adverse events (TEAEs) during the safety run-in observation period
Time Frame: Up to 35 days
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Up to 35 days
|
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Severity of TEAEs during the safety run-in observation period
Time Frame: Up to 35 days
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Up to 35 days
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Complete response (CR) as determined by the investigator
Time Frame: Up to 7 years
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Up to 7 years
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Minimal residual disease (MRD) negativity
Time Frame: At 12 months
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At 12 months
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MRD negativity
Time Frame: At 24 months
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At 24 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: Up to 7 years
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Up to 7 years
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Duration of response (DOR)
Time Frame: Up to 7 years
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Up to 7 years
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Frequency of TEAEs during expansion part
Time Frame: Up to 7 years
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As assessed by the NCI-CTCAE grading system version 5 (for all grades)
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Up to 7 years
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Severity of TEAEs during expansion part
Time Frame: Up to 7 years
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As assessed by the NCI-CTCAE grading system version 5 (for all grades)
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Up to 7 years
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Frequency of serious adverse events (SAEs)
Time Frame: Up to 7 years
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Up to 7 years
|
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Severity of SAEs
Time Frame: Up to 7 years
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Up to 7 years
|
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Frequency of laboratory abnormalities
Time Frame: Up to 7 years
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Up to 7 years
|
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Severity of laboratory abnormalities
Time Frame: Up to 7 years
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Up to 7 years
|
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Overall response of partial response (PR) or better
Time Frame: Up to 7 years
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Up to 7 years
|
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Biochemical progression-free-survival (PFS)
Time Frame: Up to 7 years
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Up to 7 years
|
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MRD negativity among participants that achieve very good partial response (VGPR) or better
Time Frame: Up to 3 years after end of treatment
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Up to 3 years after end of treatment
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Sustained MRD negativity
Time Frame: Up to 3 years after end of treatment
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Up to 3 years after end of treatment
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Time from treatment initiation to date of any myeloma-defining event
Time Frame: Up to 7 years
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Up to 7 years
|
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Time from start of treatment to date of progression to MM or death
Time Frame: Up to 7 years
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Up to 7 years
|
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Time to initiation of first-line treatment for MM
Time Frame: Up to 7 years
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Up to 7 years
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Concentration of linvoseltamab in serum over time
Time Frame: Up to 2 years
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Up to 2 years
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Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time
Time Frame: Up to 2 years
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Up to 2 years
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Titer of ADAs to linvoseltamab over time
Time Frame: Up to 2 years
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Up to 2 years
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Precancerous Conditions
- Hypergammaglobulinemia
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Smoldering Multiple Myeloma
Other Study ID Numbers
- R5458-ONC-2256
- 2023-503524-11-00 (Other Identifier: EUCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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