Melphalan/Hepatic Delivery System Achieves 46% ORR in First-line Liver-Dominant Uveal Melanoma

Melphalan/HDS delivers high-dose alkylator directly into the hepatic artery with extracorporeal chemofiltration, aiming to control the liver—the first and often only metastatic site in uveal melanoma. In the expanded-access cohort (NCT05022901), 15 treatment-naïve or pre-treated patients with ≤50% liver involvement received up to six 3 mg/kg cycles every 6–8 weeks. Among 13 evaluable patients, investigator-assessed ORR was 46% (1 CR, 5 PR) and disease-control 92%; median duration of response reached 11.3 months and median PFS 14.2 months. Grade 3/4 serious AEs occurred in 20%—thrombocytopenia/febrile neutropenia, pulmonary edema, or transient ventricular tachycardia—consistent with prior perfusion data; no treatment-related deaths were reported. Historically, percutaneous hepatic perfusion with melphalan in the phase 3 FOCUS trial yielded a 36% ORR and 9.1 mo PFS, while tebentafusp’s systemic OS gain comes with only 9% responses, underscoring the potency of liver-directed chemotherapy for hepatic-dominant disease.