ASP1570 + trifluridine + tipiracil + bevacizumab

This is an experimental **combination therapy** comprising ASP1570 (a novel small-molecule inhibitor of diacylglycerol kinase zeta), trifluridine, tipiracil, and bevacizumab. - **ASP1570** is a diacylglycerol kinase zeta (DGKζ) inhibitor that enhances antitumor immunity by releasing T-cell inhibition, promoting CD8+ cytotoxic T-cell activation, and overcoming multiple immunosuppressive signals within the tumor microenvironment. - **Trifluridine + tipiracil** (marketed in combination as Lonsurf) consists of a thymidine-based nucleoside analogue (trifluridine) and a thymidine phosphorylase inhibitor (tipiracil), together functioning as cytotoxic chemotherapy by incorporating into DNA and inhibiting DNA synthesis, leading to cancer cell death. - **Bevacizumab** is a monoclonal antibody that inhibits vascular endothelial growth factor A (VEGF-A), thereby suppressing tumor angiogenesis, which limits tumor blood supply and growth. This combination has not been approved; it is being explored for investigational use in solid tumors, leveraging a multi-modal approach of immune checkpoint inhibition/restoration (ASP1570), cytotoxic DNA synthesis inhibition (trifluridine + tipiracil), and anti-angiogenic therapy (bevacizumab)[1][2][3][5][6][7].