PIVOTAL Update Reports Sustained Recurrence-Free Survival Benefit With Neoadjuvant Daromun in Melanoma

The phase III PIVOTAL trial evaluated neoadjuvant intralesional daromun (L19IL2/L19TNF) followed by surgery versus upfront surgery in 256 patients with fully resectable stage III melanoma enrolled in the European Union. Recurrence-free survival (RFS) was the primary endpoint. Most participants had recurrence after surgery, with or without radiotherapy or adjuvant systemic treatment (222; 87%); 34 (13%) had newly diagnosed metastatic disease.

At the initial analysis, with median follow-up of 21 months, daromun improved RFS compared with surgery alone (hazard ratio, 0.59; P = .005). The updated analysis extended median follow-up to 36.8 months, with a database cutoff of November 28, 2025. The abstract reports that improvements in RFS and distant metastasis-free survival remained clinically and statistically meaningful, but does not provide updated effect estimates or absolute survival rates.

Post hoc event-free survival analyses in the overall population and recurrent-disease subgroups, with or without prior systemic therapies, were reported as consistent with the primary efficacy finding. No new safety signals of concern were recorded. These results support persistence of the reported benefit, particularly in a population dominated by recurrent disease. However, the post hoc analyses are exploratory, and the abstract alone does not establish the magnitude of the updated benefit or provide detailed toxicity data.