Elizabeth Plimack, MD, MS, Fox Chase Cancer Center, Philadelphia, PA, discusses the rationale and findings of a Phase II trial of guadecitabine, a DNA hypomethylating agent, in combination with atezolizumab in patients with metastatic urothelial carcinoma (mUC) who have progressed following initial checkpoint inhibitor therapy. In this study, a hypomethylating agent was combined with checkpoint blockade with the rationale that the agent may help re-educate the immune system against the tumor as well as prevent T-cell exhaustion, however, the primary endpoint of response was not met. This interview took place at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.