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Soo Park, MD
Soo Park, MD
Posted: Thursday, July 23, 2026
Neoadjuvant therapy with daromun, an intralesional immunotherapy combination of the fusion proteins L19IL2 and L19TNF, continued to improve recurrence-free survival in patients with resectable locally advanced stage III melanoma after more than 36 months of follow-up, according to an updated analysis of the phase III PIVOTAL trial presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract LBA9517). Katharina C. Kaehler, MD, of Universitätsklinikum Schleswig-Holstein, Kiel, Germany, and colleagues also reported event-free survival sensitivity analyses that supported the primary findings.
The open-label, randomized, multicenter trial enrolled 256 efficacy-evaluable patients with skin and/or lymph node metastatic melanoma amenable to complete surgical resection. They were randomly assigned in a 1:1 ratio to receive either four weekly intralesional injections of daromun followed by surgery or upfront surgery alone.
PIVOTAL previously met its primary endpoint at a median follow-up of 21 months, demonstrating a significant improvement in recurrence-free survival with daromun vs upfront surgery (hazard ratio [HR] = 0.59; P = .005). At a median follow-up of more than 36 months, the investigators reported that daromun continued to be associated with a significant improvement in recurrence-free survival (HR = 0.60; P = .003).
An event-free survival sensitivity analysis—which counted progression to unresectable melanoma before surgery, disease recurrence, or melanoma- or treatment-related death as events—was found to yield consistent results in the overall population (HR = 0.66). Among the 224 patients (88%) with recurrent disease after prior surgery and/or systemic (neo)adjuvant treatment, the hazard ratio was 0.59 overall, 0.55 in the subset who underwent surgery and/or radiotherapy only, and 0.63 in the subset who received systemic therapy.
The rate and type of treatment-related adverse events seemed to remain consistent with previous reports. No new safety risks were identified.
“With longer [follow-up], the highly significant reduction in the risk of recurrence or death with neoadjuvant daromun in patients with locally advanced stage III melanoma is confirmed,” the investigators concluded. “The sensitivity [event-free survival] analyses provide consistent, confirmatory evidence of daromun’s efficacy….”
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
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