FDA approves melphalan as a liver-directed treatment for uveal melanoma
Regulatory approval: On August 14, 2023, the FDA approved HEPZATO KIT (melphalan for Injection/Hepatic Delivery System; Delcath Systems) as a liver-directed treatment for adult patients with uveal melanoma and unresectable hepatic metastases involving <50% of the liver, with no extrahepatic disease or limited extrahepatic disease amenable to resection or radiation. Approval was supported by the single-arm FOCUS trial (NCT02678572) reporting an independently reviewed ORR of 36.3% and median DoR of 14 months. The product has Boxed Warnings and a REMS.
FDA approval: melphalan (HEPZATO KIT) for liver-directed treatment in uveal melanoma (2023-08-14)
Type: Regulatory approval
Agency/date: US FDA, Aug 14, 2023
The FDA approved HEPZATO KIT (melphalan for Injection/Hepatic Delivery System; Delcath Systems, Inc.) as a liver-directed treatment for adult patients with uveal melanoma with unresectable hepatic metastases affecting <50% of the liver and no extrahepatic disease, or extrahepatic disease limited to bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.
Efficacy evidence: Approval was based on FOCUS (NCT02678572), a single-arm, multicenter, open-label trial in 91 patients with unresectable hepatic metastases from uveal melanoma. Key exclusions included ≥50% liver parenchyma involvement, Child-Pugh B/C cirrhosis, or hepatitis B or C. Primary outcome measures were ORR and DoR by independent central review (RECIST v1.1): ORR 36.3% (95% CI, 26.4–47) and median DoR 14 months (95% CI, 8.3–17.7).
Administration: Via the Hepatic Delivery System by hepatic artery infusion every 6–8 weeks, up to 6 infusions; recommended dose 3 mg/kg (ideal body weight), max 220 mg per treatment.
Safety/controls: Prescribing information includes Boxed Warnings for severe peri-procedural complications (hemorrhage, hepatocellular injury, thromboembolic events) and myelosuppression. HEPZATO KIT is available only through a REMS program.