GU Cancers 2026 | Membranous/cytoplasmic nectin-4 expression with EV/pembrolizumab in UC

So the same cohort of patients looked at 143 patients who had nectin-4 expression assessed by immunohistochemistry. And the question in this abstract was a little bit different from what others have looked at. You know, in historical data from EV301, most tumors had high levels of nectin-4 expression. The question we were asking in this poster was, how does the localization of Nectin-4 matter? And so there are tumors that have predominant membranous expression where the ADC can see the target, and some that have predominant cytoplasmic expression. And so we teased that out. And what was really fascinating was we saw sort of opposite correlations. So the tumors that had membranous high expression and cytoplasmic low expression, those patients had better outcomes in terms of progression-free survival and overall survival. In contrast, when we look at cytoplasmic expression, high cytoplasmic expression was associated with worse progression-free survival and overall survival. And when we look at the composite, membranous high, cytoplasmic low, versus membranous low, cytoplasmic high, we see a clear difference. So I think this has implications for the biology, perhaps, of how Nectin-4 traffics. And I think we’re just at the beginning of understanding that interplay to understand the role of Nectin-4 targeting in EV pembro-resistant tumors, which is really an important question as we’re developing several other new agents that also will target Nekted 4.