Monoclonal Gammopathy of Undetermined Significance (MGUS)Phase 2LINKER-MGUS1NCT06140524
A Proof-of-Concept Study to Learn Whether Linvoseltamab Can Eliminate Abnormal Plasma Cells That May Lead to Multiple Myeloma in Adult Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma
A Phase 2 study testing Linvoseltamab in people with Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM), run by Regeneron Pharmaceuticals at 39 sites in 7 countries.
Trial summary
This study is researching an investigational drug called linvoseltamab ("study drug") in participants at moderate risk of developing multiple myeloma (about 3 to 10% average annual risk), a group that consists of patients with precancerous conditions called High-Risk Monoclonal Gammopathy of Undetermined Significance… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM)
- What is being tested?
- Linvoseltamab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 39 sitesin 7 countries
- Study dates
- 16 Sep 2024to 18 May 2032
- Phase
- Phase 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
- HR-MGUS or NHR-SMM as defined in the protocol
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Adequate hematologic and hepatic function, as described in the protocol
- Estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73 m^2 by the Modification of Diet in Renal Disease (MDRD) equation
Who cannot join
- High-risk SMM, as defined in the protocol
- Evidence of any of myeloma-defining events, as described in the protocol
- Diagnosis of systemic light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), solitary plasmacytoma, or symptomatic MM
- Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
- Any infection requiring hospitalization or treatment with intravenous (IV) anti-infectives within 28 days of the first dose of linvoseltamab
- Uncontrolled Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection, as described in the protocol
- NOTE: Other protocol defined inclusion/exclusion criteria apply
Trial locations and contacts
39 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
39 sites in 7 countries
Spain8 sites, 8 recruiting
- Recruiting
Hospital Sant Pau
Barcelona, 08041
- Recruiting
Institut Catala dOncologia (ICO Hospitalet)
Barcelona, 08908
- Recruiting
Hospital Clinico Universitario Virgen De La Arrixaca
El Palmar, Murcia, 30120
- Recruiting
Hospital de Cabuenes
Gijón, Principality of Asturias, 33203
- Recruiting
Hospital Universitario Virgen de las Nieves
Granada, Andalusia, 18014
- Recruiting
Universitaru Hospital La Princesa
Madrid, 28006
- Recruiting
Hospital General Universitario Morales Meseguer
Murcia, 30008
- Recruiting
Hospital Universitari Mutua Terrassa
Terrassa, Barcelona, 08221
United States7 sites, 7 recruiting
- Recruiting
University of Michigan Health
Ann Arbor, Michigan, 48109
- Recruiting
Johns Hopkins Hospital
Baltimore, Maryland, 21287
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
- Recruiting
NYU Langone Health Perlmutter Cancer Center
New York, New York, 10016
- Recruiting
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
- Recruiting
University of Washington
Seattle, Washington, 98109
- Recruiting
Stony Brook University Hospital
Stony Brook, New York, 11794
Italy7 sites, 7 recruiting
- Recruiting
Azienda Ospedaliero Universitaria (AOU) SS. Antonio e Biagio e Cesare Arrigo
Alessandria, Piedmont, 15121
- Recruiting
UOC Ematologia e Terapia Cellulare - PO Mazzoni AST Ascoli Piceno
Ascoli Piceno, 63100
- Recruiting
IRCCS Ospedale Policlinico San Martino
Genoa, Genova, 16132
- Recruiting
Istituto Romagnolo per lo Studio Dei Tumori Dino Amadori
Meldola, Forli-Cesena, 47014
- Recruiting
San Paolo Hospital
Milan, Lombardy, 20142
- Recruiting
Universita degli Studi di Pavia - Fondazione IRCCS Policlini
Pavia, 27100
- Recruiting
Ospedale Santa Maria delle Croci
Ravenna, 48121
Belgium6 sites, 6 recruiting
- Recruiting
Ziekenhuis Netwerk Antwerpen Cadix, Hematology
Antwerp, 2030
- Recruiting
Algemeen Ziekenhuis (AZ) Klina
Brasschaat, Antwerpen, 2930
- Recruiting
Algemeen Ziekenhuis St Jan Brugge Oostende Av
Bruges, West-Vlaanderen, 8000
- Recruiting
AZ St.-Elisabeth Herentals vzw
Herentals, Antwerp, 2200
- Recruiting
AZ Sint Maarten Algemeen Ziekenhuis Emmaus
Mechelen, Flanders, 2800
- Recruiting
Algemeen Ziekenhuis AZ Delta
Roeselare, West-Vlaanderen, 8800
Poland6 sites, 6 recruiting
- Recruiting
University Clinical Center / Medical University of Gdansk
Gdansk, Pomeranian Voivodeship, 80-219
- Recruiting
Swietokrzyskie Centrum Onkologii
Kielce, Świętokrzyskie Voivodeship, 25-734
- Recruiting
Pratia MCM Krakow
Krakow, Malopolska, 30-510
- Recruiting
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. Mikolaja Kopernika w Lodzi (Copernicus Memorial Hospital)
Lodz, 93-513
- Recruiting
Wojewodzki Szpital Zespolony - Ludwik Rydygier Provincial Hospital
Torun, Kuyavian-Pomeranian Voivodeship, 87-100
- Recruiting
Specjalistyczny Szpital im A. Sokolowskiego w Walbrzychu
Wałbrzych, Lower Silesian Voivodeship, 58-309
Ireland3 sites, 3 recruiting
- Recruiting
Cork University Hospital
Cork, T12 EC8P
- Recruiting
Mater Misericordiae University Hospital
Dublin, D07 R2WY
- Recruiting
Galway University Hospital
Galway, Connacht, H91 YR71
France2 sites, 2 recruiting
- Recruiting
Institut Curie
Paris, Île-de-France Region, 75005
- Recruiting
Centre Hospitalier Universitaire De Poitiers
Poitiers, New Aquitaine, 86000
About this study
Official title: Phase 2 Dose-Ranging and Interception Study of Linvoseltamab in Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma
This study is researching an investigational drug called linvoseltamab ("study drug") in participants at moderate risk of developing multiple myeloma (about 3 to 10% average annual risk), a group that consists of patients with precancerous conditions called High-Risk Monoclonal Gammopathy of Undetermined Significance (HR-MGUS) and Non-High-Risk Smoldering Multiple Myeloma (NHR-SMM).
The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of HR-MGUS and NHR-SMM.
Read more
The study is looking at several other research questions, including:
- How many participants treated with linvoseltamab have improvement of their HR-MGUS or NHR-SMM?
- What side effects may happen from taking the study drug?
- How much study drug is in the 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).
- Conditions
- Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM)
- Being tested
- Linvoseltamab
- Keywords
- linvoseltamab, monoclonal immunoglobulin (M-protein), cancer interception, immunotherapy, plasma cell disorders
- Medical subject headings
- Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LinvoseltamabDrug
Also called REGN5458, Lynozyfic™
Administered per the protocol
| Study group | Role | What they receive |
|---|---|---|
| Safety Run-In (Part 1) | Experimental | Sequential groups of participants will be enrolled to assess the initial safety and tolerability of the step-up regimen leading up to the start of different full doses of linvoseltamab. Receives: Drug: Linvoseltamab |
| Expansion (Part 2) - Dose regimen 1 | Experimental | Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens Receives: Drug: Linvoseltamab |
| Expansion (Part 2) - Dose regimen 2 | Experimental | Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens Receives: Drug: Linvoseltamab |
| Expansion (Part 2) - Dose regimen 3 | Experimental | Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens Receives: Drug: Linvoseltamab |
| Expansion (Part 2) - Dose regimen 4 | Experimental | Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens Receives: Drug: Linvoseltamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Adverse Events Interest (AEI) during the safety observation period
Part 1 An AEI is a toxicity potentially related to study treatment that may preclude dose escalation or expansion according to the Bayesian Optimal Interval (BOIN) design decision rules
Measured: 35 days
Frequency of Treatment-Emergent Adverse Event (TEAEs) during the safety observation period
Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Measured: 35 days
Severity of TEAEs during the safety observation period
Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Measured: 35 days
Achievement of Complete Response (CR) as determined by the investigator
Part 2
Measured: Up to 5.5 years
Secondary outcomes (14)
Frequency of TEAEs
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Measured: Up to 5.5 years
Severity of TEAEs
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Measured: Up to 5.5 years
Frequency of Serious Adverse Events (SAEs)
Measured: Up to 5.5 years
Severity of SAEs
Measured: Up to 5.5 years
Frequency of laboratory abnormalities
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Measured: Up to 5.5 years
Severity of laboratory abnormalities
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Measured: Up to 5.5 years
Minimal Residual Disease (MRD) negativity among participants that achieve a response of CR
Measured: Up to 5.5 years
Sustained MRD negativity on an annual basis
Measured: Up to 3 years after achievement of CR
Overall response of Partial Response (PR) or better as determined by the investigator
Measured: Up to 5.5 years
Duration Of Response (DOR) as determined by the investigator
Measured: Up to 5.5 years
Biochemical Progression-Free Survival (PFS) as determined by the investigator
Measured: Up to 5.5 years
Concentration of linvoseltamab in serum over time
Measured: Up to 9 months
Incidence of Anti-Drug Antibodies (ADAs) to linvoseltamab over the study duration
Measured: Up to 5.5. years
Magnitude of ADAs to linvoseltamab over the study duration
Measured: Up to 5.5. years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2023
- Study start16 Sep 2024
- Primary completion18 May 2032 (estimated)
- Study completion18 May 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Monoclonal Gammopathy of Undetermined Significance (MGUS)Studies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 116 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06140524
- Sponsor's protocol ID
- R5458-ONC-2257
- Other IDs
- 2023-505242-25-00, 2023
- Acronym
- LINKER-MGUS1
- Status last verified
- Jul 2026
- First submitted
- 31 Oct 2023
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Dose-Ranging and Interception Study of Linvoseltamab in Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma
- ClinicalTrials.gov ID
- NCT06140524
- Acronym / sponsor ID
- LINKER-MGUS1 / R5458-ONC-2257
- Conditions
- Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM)
- Keywords
- linvoseltamab, monoclonal immunoglobulin (M-protein), cancer interception, immunotherapy, plasma cell disorders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 116 participants (estimated)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Sep 2024 (actual)
- Primary completion
- 18 May 2032 (estimated)
- Study completion
- 18 May 2032 (estimated)
- First posted
- 20 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is researching an investigational drug called linvoseltamab ("study drug") in participants at moderate risk of developing multiple myeloma (about 3 to 10% average annual risk), a group that consists of patients with precancerous conditions called High-Risk Monoclonal Gammopathy of Undetermined Significance (HR-MGUS) and Non-High-Risk Smoldering Multiple Myeloma (NHR-SMM).
The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of HR-MGUS and NHR-SMM.
The study is looking at several other research questions, including:
- How many participants treated with linvoseltamab have improvement of their HR-MGUS or NHR-SMM?
- What side effects may happen from taking the study drug?
- How much study drug is in the 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Safety Run-In (Part 1) | Experimental | Drug: LinvoseltamabSequential groups of participants will be enrolled to assess the initial safety and tolerability of the step-up regimen leading up to the start of different full doses of linvoseltamab. |
| Expansion (Part 2) - Dose regimen 1 | Experimental | Drug: LinvoseltamabParticipants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens |
| Expansion (Part 2) - Dose regimen 2 | Experimental | Drug: LinvoseltamabParticipants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens |
| Expansion (Part 2) - Dose regimen 3 | Experimental | Drug: LinvoseltamabParticipants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens |
| Expansion (Part 2) - Dose regimen 4 | Experimental | Drug: LinvoseltamabParticipants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- HR-MGUS or NHR-SMM as defined in the protocol
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Adequate hematologic and hepatic function, as described in the protocol
- Estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73 m^2 by the Modification of Diet in Renal Disease (MDRD) equation
Key exclusion criteria (7 listed)
- High-risk SMM, as defined in the protocol
- Evidence of any of myeloma-defining events, as described in the protocol
- Diagnosis of systemic light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), solitary plasmacytoma, or symptomatic MM
- Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
- Any infection requiring hospitalization or treatment with intravenous (IV) anti-infectives within 28 days of the first dose of linvoseltamab
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LinvoseltamabAlso: REGN5458, Lynozyfic™Administered per the protocol | Drug | Expansion (Part 2) - Dose regimen 1, Expansion (Part 2) - Dose regimen 2, Expansion (Part 2) - Dose regimen 3, Expansion (Part 2) - Dose regimen 4, Safety Run-In (Part 1) |
Primary outcome
Frequency of Adverse Events Interest (AEI) during the safety observation period
Time frame: 35 days
Part 1 An AEI is a toxicity potentially related to study treatment that may preclude dose escalation or expansion according to the Bayesian Optimal Interval (BOIN) design decision rules
Frequency of Treatment-Emergent Adverse Event (TEAEs) during the safety observation period
Time frame: 35 days
Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Severity of TEAEs during the safety observation period
Time frame: 35 days
Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Achievement of Complete Response (CR) as determined by the investigator
Time frame: Up to 5.5 years
Part 2
14 secondary outcomes
Frequency of TEAEs
Time frame: Up to 5.5 years
Severity of TEAEs
Time frame: Up to 5.5 years
Frequency of Serious Adverse Events (SAEs)
Time frame: Up to 5.5 years
Severity of SAEs
Time frame: Up to 5.5 years
Frequency of laboratory abnormalities
Time frame: Up to 5.5 years
Severity of laboratory abnormalities
Time frame: Up to 5.5 years
Minimal Residual Disease (MRD) negativity among participants that achieve a response of CR
Time frame: Up to 5.5 years
Sustained MRD negativity on an annual basis
Time frame: Up to 3 years after achievement of CR
Overall response of Partial Response (PR) or better as determined by the investigator
Time frame: Up to 5.5 years
Duration Of Response (DOR) as determined by the investigator
Time frame: Up to 5.5 years
Biochemical Progression-Free Survival (PFS) as determined by the investigator
Time frame: Up to 5.5 years
Concentration of linvoseltamab in serum over time
Time frame: Up to 9 months
Incidence of Anti-Drug Antibodies (ADAs) to linvoseltamab over the study duration
Time frame: Up to 5.5. years
Magnitude of ADAs to linvoseltamab over the study duration
Time frame: Up to 5.5. years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Clinical Trial Management study director
Regeneron Pharmaceuticals
39 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Linvoseltamab in people with Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM), run by Regeneron Pharmaceuticals at 39 sites in 7 countries.
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 4 inclusion and 7 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 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in Spain, United States, Italy, Belgium, Poland and 2 more countries. 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 phase mean?
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 Clinical Trials Administrator (844-734-6643, clinicaltrials@regeneron.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Adverse Events Interest (AEI) during the safety observation period (time frame: 35 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Jul 2026.