Smoldering Multiple Myeloma (SMM)Phase 2NCT05955508
A Proof-of-Concept Trial to Study the Safety and Activity of Linvoseltamab in Adult Participants With Smoldering Multiple Myeloma at High Risk of Developing Multiple Myeloma
A Phase 2 study testing Linvoseltamab in people with Smoldering Multiple Myeloma (SMM), run by Regeneron Pharmaceuticals at 17 sites in Spain.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Smoldering Multiple Myeloma (SMM)
- What is being tested?
- Linvoseltamab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 17 sitesSpain
- Study dates
- 30 Jan 2024to 25 Jan 2033
- 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
- High-risk SMM diagnosis within 5 years of study enrollment, as described 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 ≥30 mL/min/1.73 m^2
Who cannot join
- 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 intravenous 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, as described in the protocol
- 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
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
Spain17 sites
Hospital Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Clinic de Barcelona
Barcelona, 08036
Institut Catala d'Oncologia
Barcelona, 08908
Hospital Clinico Universitario Virgen De La Arrixaca
El Palmar, Murcia, 30120
University Hospital of Cabuenes
Gijón, Principality of Asturias, 33203
Hospital Universitario Virgen de las Nieves
Granada, Andalusia, 18014
Hospital General Universitario Gregorio Maranon (HGUGM) - Instituto de Investigacion Sanitaria Gregorio Maranon
Madrid, 28009
Clinica Universidad de Navarra - Madrid
Madrid, 28027
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitari Son Llatzer
Palma Mallorca, Balearic Islands, 07198
Clinica Universidad de Navarra - Pamplona
Pamplona, Navarre, 31008
Hospital Universitario Quiron Salud Madrid
Pozuelo de Alarcón, Madrid, 28223
Hospital Clinico Universitario de Salamanca
Salamanca, 37007
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008
Hospital Clinico Universitario Santiago de Compostela
Santiago de Compostela, A Coruna, 15706
University Hospital Doctor Peset
Valencia, 46017
La Fe University Hospital
Valencia, 46026
About this study
Official title: 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 the 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.
Read more
- 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 further 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 the blood at different times?
- Whether the body makes antibodies against the study drug (which could make linvoseltamab less effective or could lead to side effects)
- Conditions
- Smoldering Multiple Myeloma (SMM)
- Being tested
- Linvoseltamab
- Keywords
- Linvoseltamab, Multiple Myeloma (MM), B cell Maturation Antigen (BCMA), Bispecific antibody
- Medical subject headings
- Smoldering Multiple Myeloma, 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 | Not described Receives: Drug: Linvoseltamab |
| Expansion (Part 2) | Experimental | Not described Receives: Drug: Linvoseltamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Adverse Events of Special Interest (AESI) during the safety run-in observation period
AESI include grade 2 or higher Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS)
Measured: Up to 35 days
Frequency of Treatment-Emergent Adverse Events (TEAEs) during the safety run-in observation period
Measured: Up to 35 days
Severity of TEAEs during the safety run-in observation period
Measured: Up to 35 days
Complete Response (CR) as determined by the investigator
Measured: Up to 7 years
Minimal Residual Disease (MRD) negativity
Measured: At 12 months
MRD negativity
Measured: At 24 months
Secondary outcomes (18)
Frequency of TEAEs during expansion part
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Measured: Up to 7 years
Severity of TEAEs during expansion part
As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Measured: Up to 7 years
Frequency of Serious Adverse Events (SAEs)
Measured: Up to 7 years
Severity of SAEs
Measured: Up to 7 years
Frequency of laboratory abnormalities
Measured: Up to 7 years
Severity of laboratory abnormalities
Measured: Up to 7 years
Overall response of Partial Response (PR) or better
Measured: Up to 7 years
Duration Of Response (DOR)
Measured: Up to 7 years
Biochemical Progression-Free-Survival (PFS)
Measured: Up to 7 years
MRD negativity among participants that achieve Very Good Partial Response (VGPR) or better
Measured: Up to 3 years after end of treatment
Sustained MRD negativity
Measured: Up to 3 years after end of treatment
Time from treatment initiation to date of any myeloma-defining event
Measured: Up to 7 years
Time from start of treatment to date of progression to MM or death
Measured: Up to 7 years
Time to initiation of first-line treatment for MM
Measured: Up to 7 years
Overall Survival (OS)
Measured: Up to 7 years
Concentration of linvoseltamab in serum
Measured: Up to 2 years
Incidence of Anti-Drug Antibodies (ADAs) to linvoseltamab
Measured: Up to 2 years
Magnitude of ADAs to linvoseltamab
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2023
- Study start30 Jan 2024
- Primary completion25 Jan 2033 (estimated)
- Study completion25 Jan 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Smoldering Multiple Myeloma (SMM)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
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
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
- NCT05955508
- Sponsor's protocol ID
- R5458-ONC-2256
- Other IDs
- 2023-503524-11-00, 2023
- Status last verified
- Apr 2026
- First submitted
- 13 Jul 2023
- Last updated
- 13 Apr 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 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Linvoseltamab in Patients With Smoldering Multiple Myeloma at High Risk of Progression to Multiple Myeloma
- ClinicalTrials.gov ID
- NCT05955508
- Acronym / sponsor ID
- R5458-ONC-2256
- Conditions
- Smoldering Multiple Myeloma (SMM)
- Keywords
- Linvoseltamab, Multiple Myeloma (MM), B cell Maturation Antigen (BCMA), Bispecific antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Jan 2024 (actual)
- Primary completion
- 25 Jan 2033 (estimated)
- Study completion
- 25 Jan 2033 (estimated)
- First posted
- 21 Jul 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 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 the 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 further 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 the blood at different times?
- Whether the body makes antibodies against the study drug (which could make linvoseltamab less effective or could lead to side effects)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Safety Run-In (Part 1) | Experimental | Drug: Linvoseltamab |
| Expansion (Part 2) | Experimental | Drug: Linvoseltamab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- High-risk SMM diagnosis within 5 years of study enrollment, as described 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 ≥30 mL/min/1.73 m^2
Key exclusion criteria (8 listed)
- 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 intravenous anti-infectives within 28 days of first dose of study drug
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), Safety Run-In (Part 1) |
Primary outcome
Frequency of Adverse Events of Special Interest (AESI) during the safety run-in observation period
Time frame: Up to 35 days
AESI include grade 2 or higher Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS)
Frequency of Treatment-Emergent Adverse Events (TEAEs) during the safety run-in observation period
Time frame: Up to 35 days
Severity of TEAEs during the safety run-in observation period
Time frame: Up to 35 days
Complete Response (CR) as determined by the investigator
Time frame: Up to 7 years
Minimal Residual Disease (MRD) negativity
Time frame: At 12 months
MRD negativity
Time frame: At 24 months
18 secondary outcomes
Frequency of TEAEs during expansion part
Time frame: Up to 7 years
Severity of TEAEs during expansion part
Time frame: Up to 7 years
Frequency of Serious Adverse Events (SAEs)
Time frame: Up to 7 years
Severity of SAEs
Time frame: Up to 7 years
Frequency of laboratory abnormalities
Time frame: Up to 7 years
Severity of laboratory abnormalities
Time frame: Up to 7 years
Overall response of Partial Response (PR) or better
Time frame: Up to 7 years
Duration Of Response (DOR)
Time frame: Up to 7 years
Biochemical Progression-Free-Survival (PFS)
Time frame: Up to 7 years
MRD negativity among participants that achieve Very Good Partial Response (VGPR) or better
Time frame: Up to 3 years after end of treatment
Sustained MRD negativity
Time frame: Up to 3 years after end of treatment
Time from treatment initiation to date of any myeloma-defining event
Time frame: Up to 7 years
Time from start of treatment to date of progression to MM or death
Time frame: Up to 7 years
Time to initiation of first-line treatment for MM
Time frame: Up to 7 years
Overall Survival (OS)
Time frame: Up to 7 years
Concentration of linvoseltamab in serum
Time frame: Up to 2 years
Incidence of Anti-Drug Antibodies (ADAs) to linvoseltamab
Time frame: Up to 2 years
Magnitude of ADAs to linvoseltamab
Time frame: Up to 2 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 13 Apr 2026.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Related trials for Smoldering Multiple Myeloma (SMM)
RecruitingPhase 3
A Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM)
High Risk Smoldering Multiple Myeloma (HR-SMM)
RecruitingObservational study
The Indiana Myeloma Registry
Plasma Cell Dyscrasias
RecruitingObservational study
Screening for AL Amyloidosis in Smoldering Multiple Myeloma
Smoldering Multiple Myeloma
RecruitingPhase 2
Isatuximab and Iberdomide as Immunotherapy for High Risk in Smouldering Myeloma
Smouldering Myeloma
RecruitingObservational study
Observational Prospective Research Study In Monoclonal Gammopathies leadINg to Myeloma
Monoclonal Gammopathy of Undetermined Significance, Smoldering Plasma Cell Myeloma
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. This study is not recruiting at the moment.
Clinical Trial Management study director
Regeneron Pharmaceuticals
17 sites in 1 country: 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 Smoldering Multiple Myeloma (SMM), run by Regeneron Pharmaceuticals at 17 sites in Spain.
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 8 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: under way, not looking for participants, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Spain. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Adverse Events of Special Interest (AESI) during the safety run-in observation period (time frame: Up to 35 days). The study lists 6 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 13 Apr 2026.