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

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

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.

The research process

The trial runs in 10 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 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. Step 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. Step 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. Step 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. Step 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. Step 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. Step 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. Step 8

    Recording of adverse events

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

  9. Step 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. Step 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 trial?

6 criteria

  • 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 trial?

6 criteria

  • 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.
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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.

What is already known about the treatment

  • Linvoseltamab

    This medication is given by intravenous infusion as a clear solution. It is still investigational and is being studied in clinical trials, so it is not yet approved for general use. It is being tested for people with high‑risk smoldering multiple myeloma, a condition that can develop into full‑blown cancer. Linvoseltamab works by attaching to a protein called BCMA on abnormal plasma cells and directing the immune system to destroy those cells; it belongs to the class of monoclonal antibody immunotherapies.

  • Darzarlex 1800 mg solution for injection

    This drug is administered by a subcutaneous injection as a ready‑to‑use solution. It is an approved, orphan‑designated medication already used to treat multiple myeloma. In this trial it is used as a comparator for patients with high‑risk smoldering multiple myeloma. Daratumumab binds to the CD38 protein on plasma cells, signaling the immune system to eliminate them, and it is classified as an anti‑CD38 monoclonal antibody.

Investigated diseases

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 detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2025-523252-31-00Protocol codeR5458-HM-24145Estimated enrolment270 patientsSponsorRegeneron Pharmaceuticals Inc.

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