In a significant advancement for patients with metastatic uveal melanoma, the CHOPIN Phase 2 trial demonstrates that combining percutaneous hepatic perfusion with melphalan using Delcath’s CHEMOSAT system and systemic ipilimumab plus nivolumab more than triples 1-year progression-free survival and nearly doubles 2-year overall survival compared to perfusion alone, though with increased but manageable higher-grade adverse events.
Groundbreaking Results from Prestigious Publication
The recent publication in The Lancet Oncology of the full results from the CHOPIN randomized Phase 2 trial marks a key milestone in the treatment landscape for metastatic uveal melanoma (mUM), a rare and aggressive form of eye cancer that frequently spreads to the liver. This investigator-initiated study, conducted at Leiden University Medical Center under Principal Investigator Professor Ellen Kapiteijn, MD, evaluated the efficacy and safety of Delcath Systems’ percutaneous hepatic perfusion (PHP) with melphalan—delivered via the CHEMOSAT Hepatic Delivery System—either alone or in combination with the immune checkpoint inhibitors ipilimumab and nivolumab.
The trial enrolled 76 patients with mUM, randomized equally into two arms of 38 patients each. Both groups received two PHP treatments with melphalan at weeks 1 and 7. In the combination arm, patients also received ipilimumab (1 mg/kg) plus nivolumab (3 mg/kg) at weeks 0, 3, 6, and 9, without subsequent maintenance therapy. The study focused on patients with liver-dominant disease, where traditional systemic therapies have historically shown limited success due to the unique biology of uveal melanoma metastases.
The primary endpoint was 1-year progression-free survival (PFS) in the intention-to-treat population. Results showed a striking improvement in the combination arm: 54.7% (95% CI 36.8–69.5) compared to 15.8% (95% CI 5.8–30.1) in the PHP-alone arm. This translated to an adjusted hazard ratio of 0.34 (95% CI 0.19–0.60; p=0.0002), indicating a substantial reduction in the risk of progression or death. Median PFS was extended to 12.8 months in the combination group versus 8.3 months with perfusion alone.
Overall survival (OS) data further reinforced the benefit of the combination approach. Median OS reached 23.1 months in the combination arm compared to 19.6 months in the PHP-alone arm, with a hazard ratio of 0.39 (95% CI 0.20–0.77; p=0.0065). At the 2-year mark, OS rates were 49.6% versus 22.1%, nearly doubling the proportion of patients surviving beyond two years.
Tumor response rates highlighted deeper and more durable anti-cancer effects in the combination therapy group. The objective response rate (ORR) was 76.3% versus 39.5%, while complete response (CR) rates stood at 13% compared to 3%. These improvements suggest synergistic effects between the liver-directed high-dose melphalan delivery and systemic immune activation, potentially enhancing hepatic tumor control and systemic disease management.
Safety Profile and Adverse Events
Safety analyses included all treated patients, with adverse events graded per Common Terminology Criteria for Adverse Events version 5.0. Grade 3 or higher treatment-related adverse events occurred in 82% of patients in the combination arm, significantly higher than the 41% in the PHP-alone arm (p=0.0006). Common severe events in the combination group included thrombocytopenia (34% vs 14%), leukopenia (26% vs 14%), elevated γ-glutamyl transferase (18% vs 8%), and anemia (13% vs 3%). Most events were self-limiting or manageable with standard supportive care, and no new safety signals emerged beyond those expected from the individual therapies.
One treatment-related death occurred in the combination arm, attributed to immune-related triple M syndrome. The overall toxicity profile aligned closely with prior reports from similar regimens, including the FOCUS trial, where severe adverse event rates were around 81%. While the addition of immunotherapy increased adverse event frequency, the benefits in survival and response appeared to outweigh these risks for many patients in this challenging disease setting.
Key Trial Outcomes Comparison
| Endpoint | Combination Arm (PHP + Ipi/Nivo) | PHP Alone Arm | Statistical Significance |
|---|---|---|---|
| 1-Year PFS | 54.7% (95% CI 36.8–69.5) | 15.8% (95% CI 5.8–30.1) | Adjusted HR 0.34 (95% CI 0.19–0.60); p=0.0002 |
| Median PFS | 12.8 months | 8.3 months | – |
| Median OS | 23.1 months | 19.6 months | HR 0.39 (95% CI 0.20–0.77); p=0.0065 |
| 2-Year OS | 49.6% | 22.1% | – |
| Objective Response Rate (ORR) | 76.3% | 39.5% | – |
| Complete Response (CR) Rate | 13% | 3% | – |
| Grade 3+ Treatment-Related AEs | 82% | 41% | p=0.0006 |
The median follow-up was 24.9 months (IQR 15.4–36.0), providing robust long-term insights. The trial, registered under ClinicalTrials.gov (NCT04283890) and EudraCT (2018-004248-49), is ongoing but no longer enrolling patients.
These findings build on earlier topline data presented at the 2025 ESMO Congress and underscore the potential of integrating liver-directed therapies with immunotherapy to address the liver-dominant nature of mUM metastases. For patients facing limited options, where systemic immunotherapies alone often yield modest results, this combination offers a promising avenue for improved disease control and prolonged survival.
Disclaimer: This article is for informational purposes only and does not constitute medical advice, investment recommendation, or endorsement of any product or therapy. Clinical trial results should be discussed with qualified healthcare professionals, and individual outcomes may vary.
