ESMO 2025 | Two-year EFS & biomarker insights from the NADINA trial in resectable melanoma

The Phase 3 NADINA trial is an investigator-initiated trial that randomized between neoadjuvant ipilimumab plus nivolumab and the response-driven adjuvant treatment after surgery versus the then standard of care, which was upfront therapeutic lymph node dissection followed by adjuvant nivolumab. So already in 2024, we have presented the final statistical analysis of the primary endpoint, which is the event-free survival, which was significantly superior for the neoadjuvant arm over the adjuvant arm. And this year at ESMO, we present an updated event-free and disease-free survival, as well as the very first biomarker results. So regarding the event-free and disease-free survival, with now a median follow-up of 25 months, we did see a prolongation of the superior effect of the neoadjuvant arm over the adjuvant arm. For example, the estimated two-year EFS for the neoadjuvant arm was 77.3% versus 55.7% for the adjuvant arm, resulting in a hazard ratio of 0.40 at this landmark. And for the disease-free survival, we did see also a continued benefit with the neoadjuvant arm. Now, moving forward to the biomarkers, of course, this is the very first time we could present those analyses, and we’re very proud of that. We have analyzed now three biomarkers that are very promising across immune oncology, but specifically also in the neoadjuvant setting for melanoma. And these biomarkers are the tumor mutational burden, the 10-gene mRNA interferon gamma signature, and PD-L1 expression, an absolute classic in that regard, of course. And for all these three biomarkers, we did see that the favorable subgroups, we used, of course, cutoffs, that the favorable subgroups did better than the unfavorable subgroups in a significant manner for both the neoadjuvant and the adjuvant arm. Although for TMB, it was not entirely significant, but we did still see a trend in that regard. And also in the neoadjuvant arm, these patients had better pathological responses, which is a secondary endpoint in this trial. But also importantly, for both the favorable and unfavorable biomarker subgroups, we did see that the neoadjuvant arm was performing better than the adjuvant arm. So none of these biomarkers, and that was also exactly what we expected, but none of these biomarkers would suggest that any patient would benefit from adjuvant treatment. So concluding at this analysis, we have continued benefit with the neoadjuvant treatment for the EFS and the DFS. We do see very good outcomes for those that have favorable biomarker profiles at baseline. And we also think we can combine some of those biomarkers to further identify the best performing patients, those that have the best response to the treatment, and also those that have the worst responses. And it really provides probably a window of opportunity to escalate and de-escalate treatments for these patients, which is really a starting point for further research to have a personalized neoadjuvant treatment in the future.

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