Background: Myelodysplastic syndrome (MDS) is a group of clonal bone marrow disorders associated with an increased risk of transformation to acute myeloid leukemia (AML). Despite recent progress in the treatment of MDS, therapeutic options are still limited, particularly for patients who fail to respond or relapse during treatment with hypomethylating agents and thus have poor survival rates. The programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway is an important checkpoint used by tumor cells to block antitumor responses. PD-L1 is present on myeloblasts during progression from MDS to AML, and its expression is enhanced by hypomethylating agents, providing the rationale for targeting PD-L1 in MDS. MEDI4736 is a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity. Methods: This Phase 1, multicenter, open-label, dose-escalation, and dose-expansion study (NCT02117219) evaluates the safety/tolerability of IV MEDI4736 in patients with pathologically confirmed MDS and Eastern Cooperative Oncology Group performance status of 0-2 who failed to respond, relapsed after an initial response, or were unable to tolerate hypomethylating agents. The primary objective is to assess the safety and tolerability of MEDI4736. Secondary objectives include: evaluation of clinical outcome in patients with MDS (International Working Group 2006 MDS response criteria), analysis of pharmacokinetics and immunogenicity of MEDI4736, and effect on patient-reported outcomes. Recruitment is ongoing, with a target enrollment of approximately 70 patients across 11 centers (United States, Germany, and United Kingdom). Clinical trial information: NCT02117219