Daromun Extends RFS in Resectable Melanoma

The updated phase III PIVOTAL analysis was published in the Journal of Clinical Oncology. It found that neoadjuvant intralesional daromun (L19IL2/L19TNF) followed by surgery improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus up-front surgery in adults with resectable, locally advanced melanoma.

Investigators randomly assigned 256 adults with at least one injectable skin or nodal lesion 1:1. The daromun group (n = 127) received intralesional treatment once weekly for up to 4 weeks before surgery; the control group (n = 129) underwent up-front surgery. The primary outcome was RFS assessed by blinded independent central review (BICR). Secondary end points included DMFS, overall survival, and safety; event-free survival (EFS) was analyzed post hoc.

At a median follow-up of 36.8 months, BICR-assessed RFS favored daromun (hazard ratio [HR], 0.55; 95% CI, 0.38-0.78; P < .001). Median RFS was 23.8 months with daromun plus surgery and 6.5 months with surgery alone. DMFS also favored daromun (HR, 0.53; 95% CI, 0.33-0.83; P = .005). The post hoc EFS analysis yielded an HR of 0.71 (95% CI, 0.51-0.98; P = .034).

Grade 3 or higher adverse events occurred in 33.6% of safety-evaluable patients in the daromun arm and 11.3% in the control arm. Grade 3 treatment-related adverse events occurred in 28.7% and 7.3%, respectively. Injection-site reaction was the most frequent grade 3 treatment-related event with daromun, occurring in 12.3%. No treatment-related events above grade 3 or treatment-related deaths were reported.

The authors cited the open-label design, exploratory subgroup analyses, and immature overall survival data as limitations. They said longer follow-up is required to clarify effects on survival and called for prospective investigation in nodal-positive patients.

Source: Hauschild A, Hassel JC, Ziemer M, et al. Neoadjuvant intralesional daromun (L19IL2/L19TNF) in resectable locally advanced melanoma: an update on the efficacy and safety results of the PIVOTAL phase III trial. J Clin Oncol. Published online August 11, 2026. doi:10.1200/JCO-26-00852