(UroToday.com) Given multiple lines of evidence supporting the efficacy of immunotherapy in urothelial cancers, there is interest in identifying therapeutic strategies that can augment patient outcomes. The Inducible T-cell co-stimulator (ICOS) protein is a member of the CD28 immunoglobulin receptor superfamily, which is the same receptor superfamily that CTLA-4 and PD-1 belong to. ICOS is expressed in urothelial cancers at high levels across all stages of disease and is induced on T-cells following activation of the T-cell receptor. Interestingly, higher expression of ICOS on CD4+ T cells is observed after anti-CTLA4 immunotherapy in urothelial cancers. In melanoma and mesothelioma, tumors expressing higher levels of ICOS tended to have more response and longer survival when treated with anti-CTLA4 monotherapy. Feladilimab is a humanized IgG4 monoclonal antibody that agonizes T-cell activity through the ICOS receptor and does not deplete T-cells. In refractory melanoma and head and neck squamous cell cancers, Feladilimab showed single-agent antitumor activity when administered after PD-1 axis immunotherapy.