ESMO 2025 | How can soluble MAdCAM-1 serve as a biomarker in metastatic RCC?

So first, it’s a pleasure today to present my work and to discuss my presentation with Vijay Oncology. My work is a multi-central international collaboration that is evaluating MAdCAM-1 as a soluble biomarker in patients with metastatic phyllodes sarcoma across three independent clinical trials. So as a way of background, MAdCAM-1, or mucosal addressin cellular adhesion molecule 1, is a protein that is expressed on ileal tissue. And it has been shown through different studies that the MADCAM1 alpha-4 beta-7 integrin is influential in lymphocyte trafficking across the gut and secondary lymphoid tissues. And in this work, we evaluated whether MAdCAM-1 levels circulating in the plasma of patients across three clinical trials could predict clinical outcomes in patients with metastatic urothelial carcinoma. To do that, we measured plasma levels of MAdCAM-1 from the JAVELIN-RENAL-101 trial, which was a phase three trial that randomized patients to first-line Sunitinib versus Avelumab plus Axitinib, as well as the SURF trial, which examined first-line Sunitinib, and the NIVOREN trial, which examined Nivolumab following prior anti-angiogenic therapy. And we show that at baseline, higher levels of MAdCAM-1 were associated with better survival in the discovery cohort of JAVELIN Renal 101, and that was also the case in the two validation cohorts which support the use of MAdCAM-1 as a prognostic biomarker. And importantly, soluble MAdCAM-1 is a dynamic biomarker, as patients who had persistently low MAdCAM-1 levels three months after systemic therapy had significantly poorer overall survival. Finally, we also show that lower levels of MAdCAM-1 were associated with inflammatory microbial signatures and especially with overgrowth of Enterococcus species.

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