Background: The success of immune checkpoint inhibitors in various cancers has triggered the identification of novel approaches to modulate the immune system. CD73, an ectonucleotidase, catalyzes the rate-limiting step for the production of adenosine in the extracellular space. Adenosine may aid tumors in evading immune recognition and destruction. MEDI9447 is a human IgG1λ monoclonal antibody (mAb) that selectively binds to and inhibits the ectonucleotidase activity of CD73. Durvalumab (MEDI4736) is a selective, high-affinity human IgG1 mAb that blocks PD-L1 binding to PD-1 (IC₅₀ 0.1 nM) and CD80 (B7.1; IC₅₀ 0.04 nM). Preclinical data suggests additive activity of MEDI9447 with checkpoint inhibitor antibodies.¹Methods: This is a first-time-in-human Phase 1, multicenter, open-label, dose-escalation and dose-expansion study (NCT02503774) of MEDI9447 administered as a single agent or in combination with durvalumab. Eligible patients include those with selected advanced solid tumors that have progressed, are refractory to, or are intolerant to standard therapy appropriate for the specific tumor type. The primary objectives are to assess safety and tolerability, describe dose-limiting toxicity (DLT), and determine the maximum tolerated dose. The secondary objectives are to evaluate antitumor efficacy, pharmacokinetics, immunogenicity, and biomarker activity in tumor biopsy specimens. Antitumor activity is assessed using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Subjects in the monotherapy arm will receive one of four dose levels of MEDI9447; subjects in the combination arm will receive one of four dose levels of MEDI9447 and a fixed dose level of durvalumab. Subjects will receive MEDI9447 as monotherapy or in combination with durvalumab for up to 52 weeks. Dose escalation will follow a 3 + 3 design. Recruitment is ongoing. 1. Cancer Res 2015;75(15 Suppl):Abstract nr 285. doi:10.1158/1538-7445.AM2015-285 Clinical trial information: NCT02503774