Multinational phase 3 trial of neoadjuvant intralesional daromun in resectable locally advanced melanoma: update on PIVOTAL results

The multinational phase 3 PIVOTAL trial evaluated daromun (combination of the targeted immunocytokines L19IL2 and L19TNF) as neoadjuvant intralesional therapy for patients with fully resectable stage III melanoma. The trial enrolled 256 patients and met its primary endpoint, demonstrating a statistically significant improvement in recurrence-free survival (RFS; HR 0.59; p=0.005) for daromun followed by surgery versus upfront surgery, at a median follow-up of 21 months. Updated analysis, at a median follow-up of 36.8 months, has now been published. Neoadjuvant daromun improved RFS (HR 0.55; p<0.001), distant metastasis-free survival (HR 0.53; p=0.005), and event-free survival (HR 0.71; p <0.034). Daromun also improved event-free survival in the subgroup of patients with recurrence after surgery with or without radiotherapy and/or adjuvant systemic therapies (n=222). Overall survival data were immature (37 of 104 events recorded). No new safety signals were observed. The authors conclude that the updated analysis confirms the clinically and statically meaningful improvements in outcomes with neoadjuvant daromun.