Phase 3 study comparing linvoseltamab and daratumumab in high‑risk smoldering multiple myeloma patients

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What is this study about?

The study focuses on High Risk Smoldering Multiple Myeloma (HR‑SMM), an early form of a blood cancer that has a higher chance of turning into full‑blown multiple myeloma. Two medicines are being compared: the investigational drug Linvoseltamab, given by intravenous infusion, and the approved medicine Daratumumab, given by subcutaneous injection. The purpose of the trial is to see which treatment can keep the disease from progressing for a longer time.

Participants will receive a series of scheduled treatment visits where the assigned medication is administered, followed by regular check‑ups that include blood tests and other simple exams to monitor the disease and any side effects. The study lasts for several years, with visits occurring at set intervals, and ends when the participant stops the medication or the study concludes.

1 enrollment confirmation

after agreeing to take part, the study team records consent and confirms that the participant meets the criteria for high‑risk smoldering multiple myeloma.

2 baseline evaluation

a series of medical examinations are performed, including blood tests, imaging studies, and questionnaires that measure quality of life.

the results create a reference point for later comparison during the study.

3 random assignment to treatment group

the participant is randomly placed into one of two groups: the linvoseltamab group or the daratumumab group.

randomization ensures that the comparison between the two medicines is unbiased.

4 initial medication administration

if assigned to the linvoseltamab group, the drug is given as an intravenous infusion of a solution for infusion; the listed dose is 0 mg, indicating that the exact therapeutic dose will be determined by the study protocol.

if assigned to the daratumumab group, the drug is given as a subcutaneous injection of 1800 mg in a solution for injection.

5 repeated medication dosing

the participant receives additional doses of the assigned medication according to the study schedule.

the frequency and total duration of dosing follow the protocol, which continues until disease progression, unacceptable side effects, or the planned end of the study.

6 regular monitoring visits

at each visit, blood samples are taken to measure disease markers and drug levels in the blood.

questionnaires are completed again to track changes in quality of life and physical functioning.

any new symptoms or side effects are recorded.

7 assessment of disease status

the study team evaluates both clinical and biochemical progression‑free survival using the international myeloma working group (imwg) criteria.

these assessments determine whether the disease has advanced or remained stable.

8 recording of adverse events

any treatment‑emergent adverse events (teae) or serious adverse events (sae) are documented, along with their severity.

9 continuation of treatment or early discontinuation

treatment continues as long as the participant tolerates the medication and the disease does not progress.

the study may end for an individual earlier if adverse events become unacceptable or if progression occurs.

10 final study visit and data collection

at the conclusion of the study period (estimated to end on 2033‑07‑27), a final evaluation is performed.

all collected data, including laboratory results, imaging, and quality‑of‑life scores, are entered into the study database for analysis.

Who Can Join the Study?

You must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, which means you are fully active or able to do light work.
You need a diagnosis of smoldering multiple myeloma (SMM) that meets the criteria set by the International Myeloma Working Group (IMWG). This is an early, symptom‑free stage of a blood‑cancer called multiple myeloma.
You must meet the high‑risk smoldering multiple myeloma (HR‑SMM) definition by one of the risk models used in the study. This means your disease has a higher chance of becoming active.
You must be an adult (the study includes participants in the adult age range defined by the trial).
You can be either male or female; both sexes are eligible.
You must also satisfy any other inclusion requirements that are listed in the trial’s detailed protocol.

Who Cannot Join the Study?

Evidence of myeloma‑defining events – signs that the disease is causing problems such as bone damage, high calcium levels, kidney issues, or anemia.
Diagnosis of any of the following conditions: systemic light chain amyloidosis (abnormal protein deposits in organs), Waldenström macroglobulinemia (a type of blood cancer), plasma cell leukemia (cancer of plasma cells that spreads to the blood), or soft tissue plasmacytoma (tumor of plasma cells in soft tissue).
History of a neurodegenerative condition (a disease that slowly damages the brain or nerves), progressive multifocal leukoencephalopathy (a rare brain infection), or any Central Nervous System (CNS) movement disorder (a problem that affects movement control in the brain or spinal cord).
Having had a seizure (a sudden disturbance of brain activity) at any time during the 12 months before being assigned to the study.
Previous treatment with any approved or experimental therapy aimed at a clonal plasma cell disorder – this includes standard chemotherapy, radiation therapy, drugs that modify the immune system, medicines that block protein breakdown in cells, or antibodies that target CD38. Ongoing use of other monoclonal antibodies (such as infliximab or rituximab) or any other medicine that could affect the study’s tests or results.
Any other reasons for exclusion that are specifically listed in the study protocol.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Hospital Universitario De Salamanca	Salamanca	Spain
Hospital Universitario De Navarra	Pamplona	Spain

Other Sites

Site Name	City	Country
Hospital Son Llatzer	Palma	Spain
Ebhzevmbdjof Sxid	Athens	Greece
Hztlxjra Upflpviqoingm Mejhb Txmtvntv	Terrassa	Spain
Vkqxgu dgc Rbtkm Ukszjnivdv Hufiddqs	Sevilla	Spain
Abhserbul Hasylwox	Athens	Greece
Hrzlhvbu Uropzrqfwmzjv Fnfnqxnws Jfjipas Dswg	Madrid	Spain
Uflmbaiqzw Cirrbucs Hdqxvokb Vespds Dy Lw Aerkbogp	Murcia	Spain
Hmfurcmk Ulhjkndwksrax Anobd	Vitoria	Spain
Hzpkhfqc Db Lq Siytt Ccjk I Scgh Prz	Barcelona	Spain
Hjqoimsy Unuycuatdxrhv 1w Dt Owjuyyt	Madrid	Spain
Hqojalyp Gjmsexn Ufyqorplkotpa Mmytopf Mhqjhnod	Murcia	Spain
Isrxlhxp Coyqfo Dypbtesdwhdoifljn	L'hospitalet De Llobregat	Spain
Gdsvup Nitstlpepp Tcrpofpblxocd Gcwzgr Pxnnozkeylyx	Thessaloniki	Greece
Hwhrwprf Uuyuvtdxbqysm Dq Pwvcy Aokiaatarf	Valencia	Spain
Hbambjsh Ufyuqwrqyxfjo Vpyufj Dh Ldr Nmsota	Granada	Spain
Ogyixkrq Gryrodq Cnvijo Plimex Pvju	Patras	Greece

Trial status

Country	Status	Recruitment Start
Greece	Not yet recruiting	13.09.2026
Spain	Not yet recruiting	13.09.2026

Trial locations

Investigated Drugs:

Linvoseltamab is an experimental monoclonal antibody being tested in this study. It is given through an IV infusion. The drug is designed to bind to a specific target on cancer cells and help the immune system recognize and destroy them. In this trial, it is used to see if it can keep people with high‑risk smoldering multiple myeloma from developing active disease for a longer time compared with the standard treatment.

Darzalex (daratumumab) is an approved antibody that is given by injection under the skin. It works by attaching to a protein on multiple myeloma cells and signals the immune system to kill those cells. In this study, it serves as the comparator treatment, allowing researchers to compare how well the new drug works against a known therapy in preventing disease progression.

High Risk Smoldering Multiple Myeloma – High Risk Smoldering Multiple Myeloma is an early, asymptomatic stage of plasma cell disease where abnormal plasma cells are present in the bone marrow but organ damage is not yet evident. It is identified by elevated levels of monoclonal protein in the blood or urine without the typical symptoms of multiple myeloma. Patients classified as high risk have specific laboratory and imaging features that indicate a greater likelihood of becoming active disease. Over time, the condition can evolve into symptomatic multiple myeloma, marked by bone lesions, anemia, kidney problems, or high calcium levels. The progression is monitored by regular blood tests and imaging to detect changes that signal disease activation.

Trial ID:

2025-523252-31-00

Protocol code:

R5458-HM-24145

NCT ID:

NCT07393282

Trial Phase:

Therapeutic confirmatory (Phase III)

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Phase 3 study comparing linvoseltamab and daratumumab in high‑risk smoldering multiple myeloma patients

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?