High Risk Smoldering Multiple Myeloma (HR-SMM)Phase 3LINKER-SMM2NCT07393282
A Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM)
A Phase 3 study testing Linvoseltamab and Daratumumab in people with High Risk Smoldering Multiple Myeloma (HR-SMM), run by Regeneron Pharmaceuticals at 27 sites in 5 countries.
Trial summary
This study is researching an experimental drug called linvoseltamab (also called "study drug") compared to another drug called daratumumab, in participants with Smoldering Multiple Myeloma (SMM), who are at a High Risk (HR) of developing active multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Risk Smoldering Multiple Myeloma (HR-SMM)
- What is being tested?
- Linvoseltamab and Daratumumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- 27 sitesin 5 countries
- Study dates
- 21 May 2026to 27 Jul 2033
- Phase
- Phase 3
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
- Eastern Cooperative Oncology Group performance status score ≤1
- SMM diagnosis per IMWG criteria as defined in the protocol
- Meets HR-SMM criteria by 1 of the risk models as defined in the protocol
Who cannot join
- Evidence of myeloma-defining events attributable to the underlying plasma cell dyscrasia, as defined in the protocol
- Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), plasma cell leukemia, or soft tissue plasmacytoma
- History of neurodegenerative condition, progressive multifocal leukoencephalopathy, or Central Nervous System (CNS) movement disorder
- History of a seizure within the 12 months of randomization
- Prior exposure to any approved or investigational treatments directed against a clonal plasma cell disorder (including but not limited to conventional chemotherapies, radiotherapy, immunomodulatory drugs, proteasome inhibitors, anti-CD38 antibodies). Ongoing treatment with other monoclonal antibodies (eg, infliximab, rituximab) or other treatments likely to interfere with study procedures or results, as described in the protocol.
- NOTE: Other protocol defined inclusion/exclusion criteria apply
Trial locations and contacts
27 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
27 sites in 5 countries
United States9 sites, 9 recruiting
- Recruiting
Emory University - Winship Cancer Institute
Atlanta, Georgia, 30322
- Recruiting
Dana Farber / Harvard Cancer Center
Boston, Massachusetts, 02215
- Recruiting
Ohio State University
Columbus, Ohio, 43210
- Recruiting
Barbara Ann Karmanos Cancer Institute - Detroit
Detroit, Michigan, 48201
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
- Recruiting
Columbia University Medical Center
New York, New York, 10032
- Recruiting
Mayo Clinic Phoenix, Mayo Clinic Building
Phoenix, Arizona, 85054
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
- Recruiting
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110
South Korea7 sites, 7 recruiting
- Recruiting
Chonnam National University Hwasun Hospital
Hwasun, Jeollanam-do, 58128
- Recruiting
Seoul National University Hospital
Seoul, 03080
- Recruiting
Severance Hospital, Yonsei University Health System
Seoul, 03722
- Recruiting
Asan Medical Center
Seoul, 05505
- Recruiting
Samsung Medical Center
Seoul, 06351
- Recruiting
Seoul St. Mary's Hospital, The Catholic University of Korea
Seoul, 06591
- Recruiting
The Catholic University of Korea, St Vincents Hospital
Suwon, Gyeonggi-do, 16247
Japan5 sites, 5 recruiting
- Recruiting
Yamanashi Prefectural Central Hospital
Kofu, Yamanashi, 400-8506
- Recruiting
National Hospital Organization Matsumoto Medical Center
Matsumoto-shi, 399-8701
- Recruiting
Nagoya City University Hospital
Nagoya, Aichi-ken, 467-8602
- Recruiting
National Hospital Organization Okayama Medical Center
Okayama, Okayama-ken, 701-1192
- Recruiting
Tokushima Prefectural Central Hospital
Tokushima, Tokushima, 770-8539
United Kingdom5 sites, 5 recruiting
- Recruiting
University Hospitals Leicester
Leicester, LE1 5WW
- Recruiting
Saint Bartholomew's Hospital
London, EC1A 7BE
- Recruiting
Hammersmith Hospital, Imperial College Healthcare NHS Trust
London, W12 0HS
- Recruiting
Norfolk and Norwich University Hospital
Norwich, Norfolk, NR4 7UY
- Recruiting
Royal Cornwall Hospital
Truro, Cornwall, TR1 3LJ
Poland1 site, 1 recruiting
- Recruiting
Pratia Onkologia Katowice
Katowice, 40-519
About this study
Official title: A Phase 3, Randomized, Open-Label Study of Linvoseltamab Versus Daratumumab in Participants With Smoldering Multiple Myeloma at High Risk of Developing Multiple Myeloma
This study is researching an experimental drug called linvoseltamab (also called "study drug") compared to another drug called daratumumab, in participants with Smoldering Multiple Myeloma (SMM), who are at a High Risk (HR) of developing active multiple myeloma.
The aim of this study is to find out whether linvoseltamab is better than daratumumab in delaying the development of MM.
The study is looking at several other research questions, including:
- 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)
- Being tested
- Linvoseltamab, Daratumumab
- Keywords
- Linvoseltamab, Multiple Myeloma (MM), B Cell Maturation Antigen (BCMA), Bispecific antibody, Smoldering Multiple Myeloma (SMM), Smoldering Myeloma, HR-SMM, Linozyfic, Darzalex
- Medical subject headings
- Multiple Myeloma, 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
DaratumumabDrug
Also called Darzalex Faspro®, Darzalex®
Administered per the protocol
| Study group | Role | What they receive |
|---|---|---|
| Linvoseltamab | Experimental | Not described Receives: Drug: Linvoseltamab |
| Daratumumab | Active comparator | Not described Receives: Drug: Daratumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) criteria
Measured: Up to 5 years
Biochemical PFS per IMWG criteria
Measured: Up to 5 years
Secondary outcomes (24)
Achievement of Minimal Residual Disease (MRD) Complete Response (CR) at 10^-5 per IMWG criteria
Measured: Up to 3 years
Time to death
Measured: Up to 9 years
Overall Response Rate (ORR) of Partial Response or better (≥PR) per IMWG criteria
Measured: Up to 3 years
Best Overall Response (BOR) per IMWG criteria
Measured: Up to 3 years
Achievement of MRD-negativity
Measured: Up to 3 years
Sustained MRD-negativity
Measured: Up to 3 years
Duration of MRD-negative CR
Measured: Up to 3 years
Duration Of Response (DOR) per IMWG criteria
Measured: Up to 5 years
Occurrence of Treatment-Emergent Adverse Events (TEAEs)
Measured: Up to 3 years
Severity of TEAEs
Measured: Up to 3 years
Occurrence of Serious Adverse Events (SAEs)
Measured: Up to 3 years
Change from baseline score in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) scale
The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported QoL using 1 GHS/QoL scale, 5 functioning scales (physical, role, emotional, cognitive and social) and 9 symptom scales / items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer.
For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 5 = "excellent" with higher scores indicating better functioning and positive changes from baseline indicate improvement.
Measured: Up to 5 years
Change from baseline score in EORTC QLQ-C30 physical functioning scale
Measured: Up to 5 years
Change from baseline score in EORTC QLQ-C30 role functioning scale
Measured: Up to 5 years
Change from baseline score in EORTC QLQ-C30 emotional functioning scale
Measured: Up to 5 years
Change from baseline score in EORTC QLQ-C30 pain scale
The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported QoL using 1 GHS/QoL scale, 5 functioning scales (physical, role, emotional, cognitive and social) and 9 symptom scales / items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer.
For the 9 symptom scales, scores range from 1 = "not at all" to 9 = "very much" higher scores indicate higher symptom burden and negative changes from baseline indicate improvement.
Measured: Up to 5 years
Change from baseline score in EORTC QLQ-C30 fatigue scale
Measured: Up to 5 years
Change from baseline score in EORTC IL478 future perspectives scale
EORTC IL478 corresponds to the EORTC QLQ-Multiple Myeloma Module 20 (MY20) future Perspective Scale. This is a is a self-administered instrument to assess QoL in persons with MM.
For the future perspective 3 items are analyzed.
A high score for an item represents a high level of symptomatic problem.
Measured: Up to 5 years
Change from baseline score in EuroQoL-5 Dimensions 5-Level Questionnaire Visual Analogue Scale (EQ-5D-5L VAS )
The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: "no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems". The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labeled "Best imaginable health state" and "Worst imaginable health state".
Measured: Up to 5 years
Functional Assessment of Cancer Therapy (FACIT)- Item Global Population 5 (GP5) responses
FACIT-Item GP5 will be used to assess the patient-reported impact of treatment toxicity that uses a single item "I am bothered by side effects of treatment" on a 5-point scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much).
Measured: Up to 5 years
Change from baseline in FACIT- Item GP5 score
Measured: Up to 5 years
Concentrations of linvoseltamab in serum
Measured: Up to 5 years
Occurrence of Anti-Drug Antibodies (ADAs) to linvoseltamab in serum
Measured: Up to 5 years
Magnitude of ADA to linvoseltamab in serum
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2026
- Study start21 May 2026
- Primary completion27 Jul 2033 (estimated)
- Study completion27 Jul 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Risk Smoldering Multiple Myeloma (HR-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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 270 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
- NCT07393282
- Sponsor's protocol ID
- R5458-HM-24145
- Other IDs
- 2025-523252-31-00, 2025
- Acronym
- LINKER-SMM2
- Status last verified
- Oct 2026
- First submitted
- 29 Jan 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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.