EphrinB2 is expressed in metastatic urothelial carcinoma (mUC) and is a gatekeeper that acts by blocking immune cell traffic; blocking ephrinB2 may be synergistic with PD1/PD-L1 immune checkpoint blockade. At the European Society for Medical Oncology (ESMO) 2021 meeting, Enrique Grande, MD, PhD, MD Anderson Cancer Center Madrid, Madrid, Spain, discusses the results of a Phase II study evaluating pembrolizumab in combination with sEphB4-HSA (B4), a B2 inhibitor in previously treated patients with mUC. the study demonstrates that the combination of B4 and pembrolizumab is well tolerated and may have synergistic efficacy. In addition, B2 expression was found to predict improved treatment outcomes in patients with mUC. This interview took place at the European Society for Medical Oncology (ESMO) 2021 congress.