Single-center phase 2 trial of adding ipilimumab and nivolumab to percutaneous hepatic perfusion for metastatic uveal melanoma

The randomized phase 2 CHOPIN trial, at Leiden University Medical Center (The Netherlands), evaluated addition of ipilimumab and nivolumab to percutaneous hepatic perfusion (PHP) for unresectable liver-only or liver-dominant metastatic uveal melanoma in patients with WHO performance status 0-1 who had no previous systemic therapy. Patients were randomized to two PHPs in weeks 1 and 7 alone (PHP group, n=38) or combination of two PHPs with ipilimumab and nivolumab in weeks 0, 3, 6, and 9 (combination group, n=38). The primary endpoint was progression-free survival (PFS) rate at one year. Median follow-up was 24.9 months (IQR 15.4-36.0). One-year PFS rate was 54.7% (95% CI 36.8-69.5) in the combination group versus 15.8% (5.8-30.1) in the PHP group (aHR 0.34; p=0.0002). Grade 3-4 treatment-related adverse events occurred in 82% of patients in the combination group and 41% of patients in the perfusion group. One treatment-related death (due to triple M syndrome) occurred in the combination group. The authors conclude that adding ipilimumab and nivolumab to PHP significantly improved PFS, but with a higher rate of adverse events.