Clinical Summary: 

• Design/Population: Updated analysis from the phase 3 PIVOTAL trial evaluating neoadjuvant intralesional immunotherapy versus upfront surgery in patients with fully resectable melanoma involving skin or lymph node metastases.
• Key Outcomes: Neoadjuvant intralesional immunotherapy continued to demonstrate substantial improvements in relapse-free survival, distant metastasis-free survival, and event-free survival after approximately 3 years of follow-up. Treatment was generally well tolerated, with adverse events primarily limited to local reactions.
• Clinical Relevance: These findings support intralesional immunotherapy as a promising neoadjuvant option for patients who relapse after prior therapy or are not candidates for conventional neoadjuvant immunotherapy approaches. 

Katharina Kaehler, MD, University of Kiel and University Hospital Schleswig-Holstein (UKSH), Kiel, Germany, discusses updated results from the phase 3 PIVOTAL trial evaluating neoadjuvant intralesional immunotherapy in patients with resectable melanoma and skin or lymph node metastases. The analysis included longer follow-up and a post hoc event-free survival assessment to further characterize the durability of treatment benefit.

Patients treated with intralesional immunotherapy experienced sustained improvements in relapse-free and distant metastasis-free survival compared with upfront surgery, while maintaining a manageable safety profile. These findings expand potential neoadjuvant treatment options for patients with melanoma, particularly those who are ineligible for or have relapsed following standard immunotherapy approaches.

Dr Kaehler presented these results at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript: 

Hello, this is Katharina Kaehler. I am here at the ASCO Annual Meeting, and I would like to talk about our presentation. 

We presented an update from the PIVOTAL phase 3 randomized trial in melanoma patients with fully resectable skin or lymph node metastases. It was amazing to see that for patients who had relapsed after, or were not eligible for, treatment with immunotherapy, neoadjuvant treatment was able to achieve absolutely remarkable relapse-free survival and distant metastasis–free survival benefits.

These findings were now confirmed by an event-free survival post hoc analysis, as well as by a longer observation period of three years. It is really encouraging to see that these patients have a meaningful treatment option available, and we are now eagerly awaiting approval.

We observed that patients treated with intralesional daromun had a more pronounced relapse-free survival benefit compared with patients undergoing upfront surgery alone, and this was achieved with a manageable safety profile consisting mainly of local adverse events. 

In current clinical practice, we generally only treat patients with neoadjuvant immunotherapy if they have not relapsed on previous adjuvant treatment. In addition, patients with preexisting autoimmune diseases are often excluded from immunotherapy approaches.

In this setting, these patients may now have access to a potential additional neoadjuvant treatment alternative, which is quite interesting and clinically relevant for them.

Source: 

Kaehler K, Ziemer M, Hassel JC, et al. Neoadjuvant intralesional daromun (L19IL2/L19TNF) in resectable locally advanced melanoma: An update on the primary outcome and sensitivity analyses (EFS) from the PIVOTAL phase 3 trial. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA9517.