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**ONO-4578 + nivolumab** is a combination therapy of a selective small molecule EP4 antagonist (ONO-4578) and a programmed cell death protein 1 (PD-1) blocking monoclonal antibody (nivolumab, also known as Opdivo). ONO-4578 antagonizes the prostaglandin E2 receptor 4 (EP4), thereby reducing immunosuppressive activity within the tumor microenvironment mediated by myeloid-derived suppressor cells and M2 macrophages, which results in enhanced activation of cytotoxic T cells[1][2][4][7]. Nivolumab blocks the PD-1 receptor on T cells, releasing immune inhibition and amplifying anti-tumor T cell responses. Preclinical and early clinical data support that the combination provides additive or synergistic anti-tumor effects in solid tumors, particularly in settings resistant to PD-1 blockade alone[1][4][7]. The combination is being investigated primarily in advanced or metastatic solid tumors, including gastric, gastroesophageal, and colorectal cancers[4][7].
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