The FDA announced approval of the Hepzato Kit melphalan injection system as Liver-directed therapy for Uveal Melanoma metastases.

The approval stipulates use in adults with unresectable liver metastases that affects less than 50% of the liver and no extrahepatic metastases or with extrahepatic disease involving bone, lymph nodes, subcutaneous tissues, or lung that can be treated with surgery or radiation. Metastatic Uveal Melanoma is a rare but aggressive metastatic cancer affecting about 1,000 people annually in the U.S. About 90% of cases involve the liver, and liver failure is a common cause of death.

National Comprehensive Cancer Network guidelines recommend liver-directed therapy for metastatic uveal melanoma with liver disease, and the Hepzato system is the first FDA-approved treatment for metastatic uveal melanoma with percutaneous infusion, according to a statement from maker Delcath Systems. The system facilitates delivery of melphalan directly to the liver by means of a novel device, achieving higher drug exposure in target tissues while limiting systemic toxicity.

Support for the approval came from the phase III single-arm FOCUS trial, which had a primary endpoint of objective response rate (ORR) and duration of response (DOR). Results for 91 patients (previously treated and untreated) showed an ORR of 36.3%, including seven complete responses, and median DOR of 14 months. The disease control rate (response plus stable disease) was 73.6%.

Prescribing information for the Hepzato Kit includes a boxed warning related to the procedure, myelosuppression, and a risk evaluation and mitigation strategy (REMS) program has been initiated to manage and mitigate risks. Serious adverse events occurred in fewer than 5% of patients, including hemorrhage, hepatocellular, and thromboembolic events. Myelosuppression associated with melphalan included thrombocytopenia, anemia, and neutropenia.

The treatment is contraindicated in patients with active brain metastases or brain lesions with a propensity to bleed; those in liver failure or with portal hypertension or known varices at risk for bleeding; patients who have undergone surgery or medical treatment of the liver in the past 4 weeks; those with certain cardiac conditions; and patients allergic to melphalan or other components of the kit.