HEPZATO Demonstrates Promising Preliminary Activity in Metastatic Ocular Melanoma

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HEPZATO KIT has demonstrated statistically significant benefit compared to best alternative care in patients with liver-dominant metastatic ocular melanoma, according to preliminary results from the phase 3 FOCUS trial.

Jonathan Zager, MD, FACS

HEPZATO KIT (HEPZATO; melphalan hydrochloride for injection/hepatic delivery system) has demonstrated statistically significant benefit compared to best alternative care (BAC) in patients with liver-dominant metastatic ocular melanoma, according to preliminary results from the phase 3 FOCUS trial (NCT02678572).1

HEPZATO was found to elicit an overall response rate (ORR) of 29.2% (95% CI, 20.1%-39.8%) per Independent Review Committee (IRC) assessment compared with 13.8% (95% CI, 3.9%-31.7%) for BAC, according to data from a preliminary analysis of 87% of enrolled patients in the intent-to-treat population. As such, HEPZATO exceeded its predefined success criteria of 21.0% for the primary ORR end point.

Additionally, the median progression-free survival (PFS) for HEPZATO was 9.0 months (95% CI, 6.2-11.8) vs 3.1 months (95% CI, 2.7-5.7) for BAC (HR, 0.41; P <.001), and the disease control rate for both arms was 70.9% (95% CI, 59.6%-80.6%) and 37.9% (95% CI, 20.7%-57.7%), respectively (P <.002).

The duration of response (DOR) and overall survival (OS) findings are not yet evaluable. Also, since not all patients were evaluable for all time points, these preliminary analyses could potentially change as the data become more mature.

“Metastatic ocular melanoma is a disease with a dismal prognosis and new therapies are urgently needed,” Jonathan Zager, MD, FACS, the lead investigator of the FOCUS study and a senior member and Director of Regional Therapies at Moffitt Cancer Center, stated in a press release. “The strength of these preliminary efficacy data, including PFS and ORR, coupled with an improved safety profile vs the first-generation product, suggests that HEPZATO would offer a compelling clinical benefit were it approved by FDA.”

HEPZATO is a drug and device combination product that was developed to administer chemotherapy to the liver at a high dose, while controlling systemic exposure and added associated adverse effects. The product is approved for sale as a standalone medical device in Europe but has yet to receive regulatory approval for sale in the United States.

The objective of the single-arm trial was to examine the efficacy of HEPZATO in patients with metastatic ocular melanoma based on the primary end. point, which was ORR per IRC assessment and RECIST v1.1 criteria; this was calculated based on analyses from 16 different publications that comprised 476 patients. Secondary end points of the trial included PFS, disease control rate, OS, and DOR.2

To be eligible for enrollment, patients needed to be 18 years of age or older with 50% or less histologically or cytologically-proven ocular melanoma metastases in the parenchyma of the liver; patients needed to have measurable disease. Patients with Child–Pugh B or C cirrhosis, portal hypertension or active cardiac conditions were excluded.

Overall, a total of 79 patients treated with HEPZATO were evaluable for response, along with 29 patients in the BAC arm. Patients were treated with either HEPZATO or BAC every 6 to 8 weeks until 6 cycles of treatment were completed, or disease progression was reported. Additionally, tumor responses were examined every 12 weeks until progression.

In terms of safety, 40.4% of patients (n = 38/94) reported serious treatment-emergent adverse effects (TEAEs). The most common serious TEAEs reported were thrombocytopenia (14.9%), neutropenia (10.6%), and leukopenia (4.2%), while 5% of patients also experienced treatment-related cardiac incidents. All serious TEAEs were resolved without complications, and no treatment-related deaths were reported.

“While the analysis is preliminary and the trial is still ongoing, these results strongly suggest that the final FOCUS dataset will demonstrate a significantly improved benefit-risk profile compared with BAC that could form the basis of our NDA resubmission to the FDA,” Gerard Michel, CEO of Delcath Systems, Inc., added in the release. “We look forward to reporting additional results later in the year as the data mature.”


  1. Delcath Systems, Inc. announces positive preliminary results from phase 3 FOCUS trial of HEPZATO in patients with metastatic ocular melanoma. News release. Delcath Systems, Inc. March 31, 2021. Accessed March 31, 2021. https://bit.ly/2QU4JHM
  2. Percutaneous hepatic perfusion in patients with hepatic-dominant occular melanoma (FOCUS). ClinicalTrials.gov. Updated September 28, 2020. Accessed March 31, 2021. https://clinicaltrials.gov/ct2/show/NCT02678572
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