FDA Approves Melphalan Injection in Hepatic-Dominant Uveal Melanoma

In the phase 3 FOCUS study, patients with hepatic dominant metastatic ocular melanoma received 3 mg/kg of melphalan administered to liver via percutaneous hepatic perfusion over 30 minutes before a 30-minute washout period.

The FDA has granted approval to melphalan injection via the Hepatic Delivery System (HEPZATO KIT) as a treatment for patients with metastatic uveal melanoma with unresectable metastases present in less than half of the liver, according to a press release from Delcath Systems, Inc.

Additionally, patients must not have extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.

The regulatory agency based its approval on findings from the phase 3 FOCUS study (NCT02678572), in which patients received melphalan during a percutaneous hepatic perfusion procedure. Among 91 patients who received treatment, the objective response rate (ORR) was 36.3% (95% CI, 26.4%-47.0%), and the median duration of response (DOR) was 14 months (95% CI, 8.3-17.7). Additionally, the disease control rate (DCR) was 73.6% (95% CI, 63.3%-82.3%), which included complete responses in 7.7% of patients and partial responses in 28.6%.

“[Melphalan via percutaneous hepatic perfusion] is the only liver-directed therapy that can treat the whole liver,” Vojislav Vukovic, chief medical officer at Delcath, said in the press release. “Scientific literature supports that [melphalan via percutaneous hepatic perfusion] may have broad applicability in other tumor types, and we intend to expand our development efforts beyond uveal melanoma given the high incidence of unresectable hepatic dominant tumors.”

The newly approved kit is designed to deliver melphalan directly to the liver via a novel system named the Hepatic Deliver System, which is hypothesized to permit higher exposure to the agent in target tissues while minimizing systemic toxicity.

In the phase 3 FOCUS study, patients with hepatic dominant metastatic ocular melanoma received 3 mg/kg of melphalan administered to liver via percutaneous hepatic perfusion over 30 minutes before a 30-minute washout period. Treatment cycles repeated every 6 to 8 weeks until disease progression.

The study’s primary end point was ORR per RECIST v1.1 criteria. Secondary end points included DOR, DCR, overall survival, and progression-free survival.

According to the press release, serious adverse effects (AEs) associated with percutaneous hepatic perfusion procedure with the melphalan kit include hemorrhage, hepatocellular injury, and thromboembolic events. These occurred in less than 5% of patients. Additionally, myelosuppressive AEs include thrombocytopenia, anemia, and neutropenia, which can be managed with standard supportive care.

“We look forward to partnering with cancer centers across the country to build a network of treatment sites trained in the use of this novel therapy,” Gerard Michael, chief executive officer at Delcath, concluded.

Reference

Delcath Systems, Inc. announces FDA approval of HEPZATO KIT™ for the treatment of adult patients with unresectable hepatic-dominant metastatic uveal melanoma. News release. Delcath Systems, Inc. August 14, 2023. Accessed August 15, 2023. prn.to/45tddGF