Hepzato Kit Approved for Unresectable Hepatic-Dominant Metastatic Uveal Melanoma

The Food and Drug Administration (FDA) has approved Hepzato Kit^™ (melphalan/Hepatic Delivery System [HDS]) as a liver-directed treatment for adult patients with metastatic uveal melanoma (mUM) with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.

The Hepzato Kit is designed to administer melphalan directly to the liver via the HDS, allowing for higher drug exposure in target tissues without an increase in systemic toxicity. While the hepatic venous blood is filtered during drug infusion and subsequent washout during a percutaneous hepatic perfusion (PHP) procedure, the HDS is able to isolate the liver resulting in locoregional delivery of a relatively high dose of the chemotherapy.

The approval was based on data from the single-arm, multicenter, open-label, phase 3 FOCUS study (ClinicalTrials.gov Identifier: NCT02678572) that evaluated the efficacy and safety of Hepzato Kit during a PHP procedure in 91 patients with hepatic-dominant ocular melanoma. Study participants received 3mg/kg of melphalan administered intraarterially using the HDS every 6 to 8 weeks for up to 6 infusions. The primary endpoint was the objective response rate (ORR). The key secondary endpoint included duration of response (DOR).

Results showed an ORR of 36.3% (95% CI, 26.4%-47.0%) in patients with hepatic and extrahepatic lesions (n = 91), of which 7.7% had complete response and 28.6% had partial response. Among responders, median DOR was 14 months (95% CI, 8.3-17.7); 70% had a DOR lasting at least 6 months and 30% had a DOR lasting at least 12 months. The disease control rate (DCR) was 73.6% (95% CI, 63.3%-82.3%).

As for safety, the most common adverse reactions (≥20%) were thrombocytopenia, fatigue, anemia, nausea, musculoskeletal pain, leukopenia, abdominal pain, neutropenia, vomiting, increased alanine aminotransferase, prolonged activated partial thromboplastin time, increased aspartate aminotransferase, increased alkaline phosphatase, and dyspnea.

The prescribing information for Hepzato Kit includes a Boxed Warning regarding the risks for severe peri-procedural complications and myelosuppression. Due to these risks, Hepzato Kit is only available through a restricted program called the Hepzato Kit Risk Evaluation and Mitigation Strategy (REMS). Patients should be evaluated for severe peri-procedural complications during and for 72 hours after administration of Hepzato, and monitored for hematologic laboratory parameters.

Hepzato Kit is supplied with the Hepzato 5×5 Drug Pack and the HDS. Each 5×5 Hepzato Kit Drug Pack includes Hepzato (mephalan) and diluents for reconstitution and dilution. The product is expected to be available in the fourth quarter of 2023.