ASTX727 + talazoparib

ASTX727 + talazoparib is an experimental **oral combination therapy** composed of ASTX727—an oral fixed-dose combination of decitabine (a DNA methyltransferase inhibitor) and cedazuridine (a cytidine deaminase inhibitor)—and talazoparib, a poly(ADP-ribose) polymerase (PARP) inhibitor. - **Mechanism of action:** Decitabine, as part of ASTX727, inhibits DNA methyltransferase 1 (DNMT1), leading to DNA hypomethylation and reactivation of silenced genes. Cedazuridine inhibits cytidine deaminase, increasing the oral bioavailability of decitabine. Talazoparib inhibits PARP, leading to accumulation of DNA single-strand breaks and synthetic lethality in tumors deficient in homologous recombination repair. The combination explores synergistic antitumor activity by promoting DNA damage (via hypomethylation and compromised repair) and inhibiting repair response (via PARP blockade), particularly in cancers with homologous recombination deficiencies or pretreated, resistant refractory disease. - The combination is under investigation in **Phase I clinical trials** for treatment of **triple negative breast cancer (TNBC)** and **hormone-resistant/HER2-negative metastatic breast cancer**[2][4][5][6][8][9]. Preclinical and early clinical data suggest enhanced efficacy through synergistic DNA damage and repair inhibition[3].

Brand names

InqoviTalzenna

Other names

decitabine/cedazuridine + talazoparib