Tremelimumab, a fully human monoclonal IgG2 antibody targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4), is being developed by Pfizer for treatment of patients with advanced cancers. Treatment with an anti-CTLA4 mAb prevents normal downregulation of T cells and prolongs T cell activation, thereby enhancing immune function. In Phase I and II studies, tremelimumab was well tolerated with predictable and manageable side effects. Antitumor activity with monotherapy was observed in patients with advanced melanoma and colorectal cancer (objective response rates of approximately 10 and 2%, respectively), and most objective responses were durable (defined as lasting > 180 days). Additional Phase II and III studies in combination with other agents will assess antitumor activity in multiple tumor types as well as attempt to identify patient populations most likely to respond.