Injectable Melphalan Hydrochloride Demonstrates Efficacy in Liver-Dominant Metastatic Ocular Melanoma


In the phase 3 FOCUS study, a positive result for a secondary end point was observed with melphalan hydrochloride for injection in patients with liver-dominant metastatic ocular melanoma.

Melphalan hydrochloride for injection/hepatic delivery system (Hepzato) was found to significantly improve overall survival in patients with liver-dominant metastatic ocular melanoma, according to a press release by Delcath Systems, Inc.

The melphalan hydrochloride delivery system was evaluated for efficacy in the phase 3 FOCUS trial (NCT02678572). The interventional study has an actual enrollment of 102 participants. The primary end point is objective response rate (ORR). Secondary end points include duration of response, disease control rate, overall survival, and progression-free survival (PFS). Other end points include time to objective response, hepatic PFS, hepatic ORR, quality of life as measured by functional hepatobiliary symptom index, and safety outcomes.

“Metastatic ocular melanoma is a disease with a dismal prognosis and new therapies are urgently needed. The FOCUS study results, along with the predefined analyses versus a relevant best alternative care [BAC] group, clarify Hepzato overall clinical benefit in this difficult-to-treat patient population,” said Jonathan Zager MD FACS, global lead investigator of the FOCUS study, senior member and director of Regional Therapies at Moffitt Cancer Center, in a press release. “The overall efficacy, coupled with an improved safety profile versus the first-generation product, suggests that Hepzato would offer a compelling clinical benefit were it approved by FDA.”

During the single-arm study, patients received 3mg/kg ideal body weight of melphalan for infusions administered directly to the liver via percutaneous hepatic perfusions over 30 minutes followed by a 30-minute washout. Treatment was repeated every 6 to 8 weeks until disease progression. A BAC, originally randomized prior to its amendment to a single-arm study in 2018, included 42 patients.

An analysis found that the ORR was 35.2% in the experimental arm and 12.5% in the BAC arm (P =.0154). The disease control rate was 73.6% in the experimental arm compared with 37.5% in the BAC arm (P =.0002). Additionally, the median PFS was 9.03 months in the experimental group versus 3.12 months in the control arm (HR, 0.39, P =.0002). While survival data is still maturing, at the time of analysis the 12-month survival in the experimental arm stood at 75% compared with 47% in the BAC arm (HR,0.37, P =.01).

Commonly reported treatment-emergent serious adverse events were anemia (29.7%), thrombocytopenia (26.4%), and neutropenia (19.8%). A little over 5 percent of patients experienced treatment-emergent serious cardiac adverse events. No treatment-related deaths were reported.

“We are thrilled by the Hepzato response rates and duration of response which far exceed that which has been seen with other agents in this difficult-to-treat patient population. Our data further highlights Hepzato’s potential superiority to other available liver-targeted therapies, which suggests a broader utility for our platform across multiple liver-metastatic tumor types. In addition to re-filing our new drug application by mid-2022, Delcath, along with key opinion leaders, intend to study Hepzato in additional indications in the near future,” said Zager.

In order to participate in the study, patients must have been 18 years of age or older, must weigh 35 kg or greater, measurable disease in the liver, evidence of limited extrahepatic disease, must not have received chemotherapy, radiotherapy, or chemoembolization within 30 days of treatment, and must have an ECOG performance status of 0 to 1 at screening. Patients with a history of clinically significant pulmonary disease, active bacterial infections, a latex allergy, or prior Whipple’s procedure, were not eligible to participate.

Delcath Systems, Inc. announces positive phase 3 focus trial results for Hepzato™ in liver-dominant metastatic ocular melanoma, including initial survival data analysis. News release. Delcath. December 2, 2021. Accessed December 6, 2021.
Percutaneous hepatic perfusion in patients with hepatic-dominant ocular melanoma (FOCUS). Accessed November 6, 2021.
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