ONO-4578 + nivolumab + gemcitabine + nab-paclitaxel

ONO-4578 + nivolumab + gemcitabine + nab-paclitaxel is an experimental four-drug combination regimen currently under investigation in cancer clinical trials, particularly for advanced solid tumors such as pancreatic cancer. - **ONO-4578** is an orally administered, highly selective small-molecule antagonist of the prostaglandin E2 receptor, subtype EP4. By blocking EP4, ONO-4578 disrupts PGE2-mediated immunosuppression in the tumor microenvironment and reduces the presence of myeloid-derived suppressor cells (MDSCs) and M2 macrophages, thereby enhancing antitumor immunity[1][3][5]. - **Nivolumab** (Opdivo) is a monoclonal antibody immune checkpoint inhibitor targeting programmed death-1 (PD-1) receptor, helping to restore T cell activity against tumors. - **Gemcitabine** is a nucleoside analog chemotherapy agent that inhibits DNA synthesis, resulting in antitumor activity. - **Nab-paclitaxel** (Abraxane) is paclitaxel bound to albumin nanoparticles, enhancing drug delivery and eliminating the need for solvents; it stabilizes microtubules and induces apoptosis in dividing cancer cells. Nab-paclitaxel may also increase gemcitabine’s effectiveness by reducing levels of its catabolic enzyme cytidine deaminase[2][6]. This combination aims to produce enhanced efficacy by modulating the tumor immune microenvironment, inhibiting immune checkpoints, and delivering synergistic cytotoxic effects. Early clinical trials for this regimen have been conducted, specifically in pancreatic and other advanced solid tumors[1][3][5].

Other names

nivolumabgemcitabinenab-paclitaxelalbumin-bound paclitaxel