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NCT Number: NCT07559799

A Non-interventional Study of Melphalan Flufenamide (Melflufen) (Pepaxti®) and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma (R/RMM)

Multiple myeloma is the second most common hematologic malignancy in adults and despite the new therapies that have been developed in the last decades it remains incurable. Over the course of the disease, patients eventually become refractory to the various treatments. Therefore, new therapeutic options which utilize new mechanisms of action are essential.

Melphalan flufenamide (melflufen) represents such an additional therapeutic approach. Melflufen is a peptide-drug conjugate (PDC) which is highly lipophilic and rapidly incorporated into the tumor cells. Once inside the tumor cell, melflufen is hydrolyzed by peptidases, including aminopeptidases and esterases, to release its alkylator payload. The alkylating agent then induces DNA damage resulting in cell death.

Melphalan flufenamid in combination with Dexamethason was approved by the European Medicines Agency (EMA) in August 2022 for the treatment of patients with triple class refractory relapsed/refractory Multiple Myeloma who have received at least 3 prior lines of therapy. For patients with prior autologous stem cell transplantation, the time to progression should be at least 3 years from transplantation.

The non-interventional study MARINA aims to address open scientific questions regarding the effectiveness, as well as therapy and safety management of melflufen in a real-world setting. By collecting comprehensive real-world data - including the Disease Control Rate (DCR) as a key endpoint, which is of most value for patients in this late disease stage - MARINA will investigate the therapeutic benefit of melflufen in routine clinical practice.

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Key information

Conditions

Multiple Myeloma Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Praxis für interdisziplinäre Onkologie & Hämatologie

Freiburg im Breisgau, Germany

Location status: Recruiting

Location contact

Patrick Marschner, Dr. med.

CONTACT

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients with R/RMM who have previously been treated with at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, and who relapsed on or after the last therapy
  • Indication and decision for fourth- or later-line treatment with melflufen (Pepaxti®) and dexamethasone, according to current SmPC as assessed by the treating physician
  • Signed and dated written informed consent*.
  • Treatment decision before inclusion into this non-interventional study
  • Age ≥18 years
  • Patients are allowed to be enrolled up to 28 days (+ 14 days) after their first dose of melflufen+dexamethasone,, but before any response assessment and second dose of melflufen+dexamethasone. These patients will not participate in the PRO assessments.

Exclusion criteria

  • Participation in an interventional clinical trial (except follow-up)
  • Patient unable to consent
  • Contraindications according to current SmPC

Treatment and study plan

Primary outcomes

  1. Disease control rate (DCR)

    Time frame: max. 38 months (FPI - LPLV)

    DCR is defined as the proportion of patients achieving a remission (i.e., sCR, CR, VGPR or PR or MR) or stable disease as best response according to local medical standards during treatment with melflufen. Patients without response measurement are considered non-responders.

Secondary outcomes

  1. Progression-free survival (PFS)

    Time frame: max. 38 months (FPI - LPLV)

    PFS is defined as the time from start of melflufen treatment until first progression or death from any cause, whichever comes first. Patients without disease progression or death at the time of analysis will be censored at their date of last contact. PFS will be calculated using the Kaplan-Meier method.

  2. Overall survival (OS)

    Time frame: max. 38 months (FPI - LPLV)

    OS is defined as the time from start of melflufen treatment until death from any cause. Patients without documented death will be censored with their date of last contact. OS will be calculated using the Kaplan-Meier method.

  3. Overall response rate (ORR)

    Time frame: max. 38 months (FPI - LPLV)

    ORR is defined as the proportion of patients achieving a remission (sCR, CR, VGPR or PR or MR) as best response according to local medical standards. Patients without response measurement are considered non-responders.

  4. Duration of treatment with melflufen

    Time frame: max. 38 months (FPI - LPLV)

    Duration of melflufen treatment will be calculated in weeks as the time from first application to the last documented application of melflufen.

  5. Clinical benefit rate (CBR)

    Time frame: max. 38 months (FPI - LPLV)

    CBR is defined as the proportion of patients achieving a sCR, CR, VGPR, PR or MR as best response according to local medical standards during treatment with melflufen. Patients without response measurement are considered non-responders.

  6. Time to next treatment (TTNT)

    Time frame: max. 38 months (FPI - LPLV)

    TTNT is defined as the time from start of melflufen treatment until start of the following therapy line or death, whichever comes first. Patients alive and without subsequent treatment at the time of analysis will be censored at their date of last contact. TTNT will be calculated using the Kaplan-Meier method.

  7. PFS2

    Time frame: max. 38 months (FPI - LPLV)

    PFS2 is defined as the time from start of melflufen treatment until progression or death during first subsequent treatment line, whichever comes first. If subsequent line is not reached, previous-line death will serve as event. Patients without progression after the start of the subsequent line or death at the time of analysis will be censored at their date of last contact. PFS2 will be calculated using the Kaplan-Meier method.

  8. PFS of first subsequent treatment line

    Time frame: max. 38 months (FPI - LPLV)

    PFS of first subsequent treatment line is defined as time from start of first subsequent treatment line until first progression thereafter, or death from any cause, whatever comes first. Patients without progression or death at the time of analysis will be censored with their date of last contact. PFS of first subsequent treatment line will be calculated using the Kaplan-Meier method.

  9. (Serious) adverse events ((S)AE)

    Time frame: max. 38 months (FPI - LPLV)

    The case- and patient-based incidence of (S)AEs will be provided.

  10. (Serious) adverse drug reactions ((S)ADR) related to melphalan flufenamid

    Time frame: max. 38 months (FPI - LPLV)

    The case- and patient-based incidence of (S)ADRs will be provided.

  11. Types of treatments prior to Melflufen

    Time frame: max. 38 months (FPI - LPLV)

    To illustrate the prior treatments, the substances administered before Melflufen are listed by treatment line.

  12. Melfalan flufenamid starting dose

    Time frame: max. 38 months (FPI - LPLV)

    Frequencies of patients with specific melflufen starting dose (i.e., 40mg, 30mg, other) will be provided.

  13. Absolute dose intensity of melphalan flufenamid

    Time frame: max. 38 months (FPI - LPLV)

    Absolute dose intensity of melphalan flufenamid will be displayed with descriptive statistics.

  14. Relative dose intensity of melphalan flufenamid

    Time frame: max. 38 months (FPI - LPLV)

    Relative dose intensity of melphalan flufenamid will be displayed with descriptive statistics.

  15. Type of dose modifications

    Time frame: max. 38 months (FPI - LPLV)

    Type of dose modifications will be displayed with descriptive statistics.

  16. Frequency of dose modifications

    Time frame: max. 38 months (FPI - LPLV)

    Frequency of dose modifications will be displayed with descriptive statistics.

  17. Reasons for dose modifications

    Time frame: max. 38 months (FPI - LPLV)

    Reasons for dose modifications will be displayed with descriptive statistics.

  18. Substances of subsequent antineoplastic treatment

    Time frame: max. 38 months (FPI - LPLV)

    Frequencies of substances used will be displayed in a summary table.

  19. Global health-related quality of life during course of treatment

    Time frame: max. 38 months (FPI - LPLV)

    The change from baseline (i.e., difference) in the scales of the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer quality of life questionnaire C30) will be displayed for each point in time, using boxplots.

  20. Multiple myeloma related quality of life during course of treatment

    Time frame: max. 38 months (FPI - LPLV)

    The change from baseline (i.e., difference) in the scales of the EORTC QLQ-MY20 (European Organisation for Research and Treatment of Cancer quality of life questionnaire MY20) will be displayed for each point in time, using boxplots.

  21. Assessing parameters of physician treatment decision making

    Time frame: max. 38 months (FPI - LPLV)

    Results of therapy decision questionnaires will be displayed with frequencies in a summary table.

Study contacts

Contact information is provided by the study sponsor or research team.

Sina Grebhardt, PhD

CONTACT

[email protected]

+49 761 / 15 242-0

Sponsors and collaborators

Lead sponsor

iOMEDICO AG

Industry

Collaborators

  • Oncopeptides AB

Registry information

Acronym: MARINA

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Apr 30, 2026
Registry last updated
Jun 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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