M6620 + cisplatin + etoposide

This is a combination regimen of three anticancer agents: **M6620 (VX-970)**, **cisplatin**, and **etoposide**. - **M6620 (VX-970)** is a first-in-class, potent, selective inhibitor of ATR (ataxia telangiectasia and Rad3-related protein), a kinase critical for DNA damage response. Inhibition of ATR impairs tumor cell repair of DNA damage, especially when combined with DNA-damaging chemotherapy. - **Cisplatin** is a platinum-based chemotherapy that induces DNA crosslinks and damage, inhibiting DNA replication and transcription. - **Etoposide** is a topoisomerase II inhibitor that induces DNA strand breaks. This combination is being explored in clinical trials for treating advanced solid tumors, with a strong rationale for tumors with defects in DNA damage response pathways (e.g., mutations in BRCA1, BRCA2, or ATM genes) because ATR inhibition can sensitize cancer cells to DNA-damaging agents and overcome resistance to platinum-based therapies. The combination of M6620 with chemotherapy leverages synthetic lethality by exacerbating DNA damage and selectively killing tumor cells with impaired DNA repair[1][2][3][5].