Journal Article

An Open-label, Randomized Study of Melphalan/Hepatic Delivery System Versus Best Alternative Care in Patients with Unresectable Metastatic Uveal Melanoma

Howard, J. Harrison, Gesierich, Anja, Rivoire, Michel, Richtig, Erika, Lowe, Michael C., Ottensmeier, Christian H., Choi, Junsung, Ejaz, Aslam, Eschelman, David J., Glazer, Evan S., John, Johnny, Ferrucci, Pier Francesco, Zager, Jonathan S., Bender, Armin, Gschnell, Martin, Sacco, Joseph J., Fenwick, Stephen William, Weishaupt, Carsten, Dummer, Reinhard, Wheater, Matthew, Reddy, Sunil A., Arance, Ana, Beasley, Georgia M., Haferkamp, Sebastian, Orloff, Marlana, Ochsenreither, Sebastian

2025

Overview

Background Metastatic uveal melanoma (mUM) has a poor prognosis, with liver metastases typically presenting a therapeutic challenge. Melphalan/Hepatic Delivery System (Melphalan/HDS) is a drug/medical device combination used for liver-directed treatment of unresectable mUM patients. This study assessed efficacy and safety of Melphalan/HDS versus best alternative care (BAC). Methods Eligible patients with unresectable mUM were randomized (1:1) to receive Melphalan/HDS (3 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of 6 cycles or BAC. Due to slow enrollment and patient reluctance to receive BAC treatment, the study design was amended to a single-arm Melphalan/HDS study, and all efficacy analyses of the randomized study were treated as exploratory. Results The study enrolled 85 patients. Eligible patients were randomized to receive Melphalan/HDS ( n = 43) or BAC ( n = 42), and 72 patients received study treatment (Melphalan/HDS [ n = 40]; BAC [ n = 32]). Exploratory analyses of efficacy endpoints showed numerical differences consistently favoring the Melphalan/HDS arm versus BAC (median overall survival: 18.5 vs. 14.5 months; median progression-free survival: 9.1 vs. 3.3 months; objective response rate: 27.5% vs. 9.4%; and disease control rate: 80.0% vs. 46.9%). Serious adverse events (SAEs) occurred in 51.2% of Melphalan/HDS and in 21.9% of BAC patients. The most common (>5%) SAEs included thrombocytopenia (19.5%), neutropenia (9.8%), leukopenia (9.8%) and febrile neutropenia (7.3%) in Melphalan/HDS patients and cholecystitis, nausea and vomiting (6.3% each) in BAC patients. No treatment-related deaths were observed. Conclusion Treatment with Melphalan/HDS shows clinically meaningful efficacy and demonstrates a favorable benefit-risk profile in patients with unresectable mUM as compared to BAC.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Adult / Aged / Antineoplastic Agents, Alkylating - administration & dosage / Bacterial artificial chromosomes / Body weight / Cholecystitis / Disease control / Drug Delivery Systems / Female / Follow-Up Studies / Hepatobiliary Tumors / Humans / Leukopenia / Liver / Liver Neoplasms - drug therapy / Liver Neoplasms - secondary / Male / Medical prognosis / Medicine / Medicine & Public Health / Melanoma / Melanoma - drug therapy / Melanoma - pathology / Melanoma - secondary / Melphalan / Melphalan - administration & dosage / Metastases / Metastasis / Middle Aged / Neutropenia / Oncology / Patients / Prognosis / Surgery / Surgical Oncology / Survival / Survival Rate / Thrombocytopenia / Uveal Melanoma / Uveal Neoplasms - drug therapy / Uveal Neoplasms - pathology