Adding Immunotherapy to PHP Shows Encouraging Efficacy in Metastatic Uveal Melanoma

Percutaneous hepatic perfusion (PHP) combined with the immune checkpoint inhibitors (ICIs) ipilimumab (Yervoy) plus nivolumab (Opdivo) produced encouraging progression-free survival (PFS) rates with manageable toxicities compared with PHP alone in patients with metastatic uveal melanoma (UM), according to findings from the phase 2 CHOPIN trial (NCT04283890) presented at the 2025 European Society for Medical Oncology (ESMO) Congress.¹

The study met its primary end point with a 1-year progression-free survival (PFS) of 54.7% (95% CI, 36.8%–69.5%) observed among patients who received the combination therapy vs 15.8% (95% CI, 5.8%–30.1%) among patients who received PHP alone.

With respect to secondary efficacy end points, at a median follow-up of 24.9 months, an overall survival (OS) of 23.1 months was achieved with the combination treatment, a significant improvement compared with 19.6 months seen with PHP alone (P =.006). Further, the best overall response rate was 81.6% and 40.5% with the combination and PHP alone, respectively.

“All in all, immune checkpoint inhibition plus [PHP] offers a promising new treatment paradigm for patients with metastatic [UM],” said Ellen Kapiteijn, Medical Oncology Department at Leiden University Medical Center, during the presentation.¹

Regarding safety, the combination demonstrated a manageable safety profile. While grade 3 or higher treatment-related adverse events (TRAEs) were more frequent with the combination treatment (81.6% vs 40.5%; P <.001), these events were mostly manageable and may have been attributable to the addition of immunotherapy, according to Kapiteijn. The combination arm also saw more treatment discontinuation due to an AE (34.2% vs 2.7%), and there was 1 ICI-related death reported in the combination arm.

What was the rationale for the CHOPIN study?

Metastatic UM is an uncommon condition characterized by high mortality rates and a paucity of treatment options, often metastasizing to the liver or lungs.^1,2 Despite the emergence of ICIs as a promising treatment option in metastatic cutaneous melanoma, this option does not hold for metastatic UM.³ Furthermore, while administration of melphalan chemotherapy via PHP has also demonstrated effectiveness in treating liver metastases, it remains ineffective against extrahepatic disease.

“Metastatic [UM] is a poor prognostic cancer and often metastasizes to the liver. In 93% [of cases], liver metastases are found, and a lot of patients have liver metastases alone,” Kapiteijn explained. “Liver-directed therapy with [PHP] is a way of supplying high-dose melphalan to the liver to treat liver metastasis. The CHOPIN trial was based on the facts that PHP is ineffective against extrahepatic disease.”

Through the CHOPIN trial, the authors sought to investigate whether there was a synergistic effect between PHP and ICIs that could enhance response and survival.

What is the CHOPIN trial investigating?

The single-center, open-label, randomized CHOPIN study is assessing the efficacy and safety of the combination of PHP-administered chemotherapy (melphalan) and ipilimumab plus nivolumab vs PHP alone in adult patients with metastatic UM.^2,3 Patients were included if they were 18 to 80 years old, had unresectable liver-only or liver-dominant disease, and had no prior systemic treatment.

The primary end point of the study was 1-year PFS; secondary end points consisted of OS, best overall response rate, and safety.

To assess these outcomes, the study randomized 76 patients 1:1 to receive either the combination or PHP alone (n = 38, each arm). All patients, regardless of assignment, underwent PHP at weeks 1 and 7. Those assigned to the combination arm received the ICIs at weeks 0, 3, 6, and 9. The maximum tolerated doses for the ICIs, 1 mg/kg of ipililumab and 3 mg/kg of nivolumab, were established in a prior phase 1b portion of the study.

The trial has an estimated completion slated for December 2029.

DISCLOSURES: Kapiteijn declared institutional receipt of consulting fees from Delcath, Immunocore, and Lilly, research fundings from BMS, Delcath, Pierre-Fabre, and Novartis, and a role as chair of the Dutch Melanoma and Skin Cancer Group/WIN-O melanoma group, the Netherlands.

REFERENCES:

1. Kapiteijn, E. Combined percutaneous hepatic perfusion with ipilimumab plus nivolumab in metastatic uveal melanoma (CHOPIN): A single-center, open-label, randomized, phase II study. Presented at: ESMO 2025 Congress; October 17–20, 2025; Berlin Germany. Abstract LBA59.

2. PHP and Immunotherapy in Metastasized UM (CHOPIN). ClinicalTrials.gov. Updated September 9, 2025. Accessed October 20, 2025. https://www.clinicaltrials.gov/study/NCT04283890

3. Tong TML, van der Kooij MK, Speetjens FM, et al. Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial. Trials. 2022 Feb 13;23(1):137. doi: 10.1186/s13063-022-06036-y. PMID: 35152908; PMCID: PMC8842930.