Phase I, open-label study of MEDI0680, an anti-programmed cell death-1 (PD-1) antibody, in combination with MEDI4736, an anti-programmed cell death ligand-1 (PD-L1) antibody, in patients with advanced malignancies.
2015
TPS3087 Background: The PD-1/PD-L1 pathway plays a key role in controlling T-cell activation and may be utilized by tumor cells to evade antitumor responses. Anti-PD-1 and anti-PD-L1 antibodies have shown acceptable safety profiles and clinical activity across a range of tumor types. MEDI0680 is a humanized IgG4κ mAb specific for human PD-1 that blocks PD-L1 and programmed cell death ligand-2 (PD-L2). Blocking both PD-L1 and PD-L2 may have more efficient blockade and may be more specific for different tumor groups in comparison to blocking either one alone. MEDI4736 is a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity. Anti-PD-1 and PD-L1 agents block distinct interactions contributing to immunosuppression, suggesting potential additive or synergistic effects. Preclinical data, including mouse models, support potential benefit for anti-PD-L1 and anti-PD-1 in combination. Methods: This phase I, multicenter, open-label study evaluates the safety of MEDI0680 in co...
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