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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Sina Grebhardt, PhD; Phone Number: +49 761 / 15 242-0; Email: info@iomedico.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥18 years old) with relapsed and/or refractory multiple myeloma (R/RMM) pretreated with a proteasome inhibitor, an immunomodulatory drug and a CD38 antibody with decision for treatment with melflufen (Pepaxti®) and dexamethasone in fourth or later line according to SmPC.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	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.	max. 38 months (FPI - LPLV)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	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.	max. 38 months (FPI - LPLV)
Overall survival (OS)	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.	max. 38 months (FPI - LPLV)
Overall response rate (ORR)	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.	max. 38 months (FPI - LPLV)
Duration of treatment with melflufen	Duration of melflufen treatment will be calculated in weeks as the time from first application to the last documented application of melflufen.	max. 38 months (FPI - LPLV)
Clinical benefit rate (CBR)	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.	max. 38 months (FPI - LPLV)
Time to next treatment (TTNT)	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.	max. 38 months (FPI - LPLV)
PFS2	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.	max. 38 months (FPI - LPLV)
PFS of first subsequent treatment line	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.	max. 38 months (FPI - LPLV)
(Serious) adverse events ((S)AE)	The case- and patient-based incidence of (S)AEs will be provided.	max. 38 months (FPI - LPLV)
(Serious) adverse drug reactions ((S)ADR) related to melphalan flufenamid	The case- and patient-based incidence of (S)ADRs will be provided.	max. 38 months (FPI - LPLV)
Types of treatments prior to Melflufen	To illustrate the prior treatments, the substances administered before Melflufen are listed by treatment line.	max. 38 months (FPI - LPLV)
Melfalan flufenamid starting dose	Frequencies of patients with specific melflufen starting dose (i.e., 40mg, 30mg, other) will be provided.	max. 38 months (FPI - LPLV)
Absolute dose intensity of melphalan flufenamid	Absolute dose intensity of melphalan flufenamid will be displayed with descriptive statistics.	max. 38 months (FPI - LPLV)
Relative dose intensity of melphalan flufenamid	Relative dose intensity of melphalan flufenamid will be displayed with descriptive statistics.	max. 38 months (FPI - LPLV)
Type of dose modifications	Type of dose modifications will be displayed with descriptive statistics.	max. 38 months (FPI - LPLV)
Frequency of dose modifications	Frequency of dose modifications will be displayed with descriptive statistics.	max. 38 months (FPI - LPLV)
Reasons for dose modifications	Reasons for dose modifications will be displayed with descriptive statistics.	max. 38 months (FPI - LPLV)
Substances of subsequent antineoplastic treatment	Frequencies of substances used will be displayed in a summary table.	max. 38 months (FPI - LPLV)
Global health-related quality of life during course of treatment	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.	max. 38 months (FPI - LPLV)
Multiple myeloma related quality of life during course of treatment	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.	max. 38 months (FPI - LPLV)
Assessing parameters of physician treatment decision making	Results of therapy decision questionnaires will be displayed with frequencies in a summary table.	max. 38 months (FPI - LPLV)

Collaborators and Investigators

• Sponsor: iOMEDICO AG
• Collaborators: Oncopeptides AB

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: April 20, 2026
• First Submitted That Met QC Criteria: April 27, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma
• Other Study ID Numbers: IOM-120481

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No