pamiparib + temozolomide

Pamiparib + temozolomide is an investigational combination therapy consisting of pamiparib, a potent and selective small molecule inhibitor of poly(ADP-ribose) polymerase 1 and 2 (PARP1/2), and temozolomide, an oral alkylating agent used in chemotherapy. Pamiparib inhibits PARP-mediated DNA repair, leading to synthetic lethality in tumor cells with homologous recombination deficiency or BRCA mutations. Temozolomide methylates DNA bases, causing damage that is normally repaired by the base excision repair pathway involving PARP; thus, combining these agents results in synergistic cytotoxicity due to accumulation of unrepaired DNA lesions. This combination has been studied primarily for recurrent gliomas with IDH1/2 mutations and other advanced solid tumors[1][2][5][6][9]. Clinical trials have shown manageable safety profiles but modest antitumor activity; hematologic toxicities are common[5][6].