peposertib + etoposide + cisplatin

A combination regimen comprising **peposertib** (M3814), **etoposide**, and **cisplatin**. Peposertib is a selective small molecule inhibitor of DNA-dependent protein kinase (DNA-PK), a key enzyme involved in the repair of DNA double-strand breaks via the non-homologous end joining pathway. Inhibiting DNA-PK impairs tumor cell DNA repair capacity, potentially enhancing the efficacy of DNA-damaging agents such as etoposide and cisplatin, which induce DNA breaks and crosslinks. Etoposide is a topoisomerase II inhibitor that causes DNA double-strand breaks, while cisplatin forms DNA adducts and crosslinks, leading to apoptosis of rapidly dividing cells. This combination is investigated primarily in cancer treatment, including advanced and refractory solid tumors, and may potentiate antitumor activity through synergistic DNA damage and DNA repair inhibition.