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Talazoparib + irinotecan is an investigational combination therapy consisting of talazoparib, a potent oral poly(ADP-ribose) polymerase (PARP) inhibitor, and irinotecan, an intravenous topoisomerase I inhibitor. Talazoparib inhibits PARP enzymes involved in DNA repair, leading to accumulation of DNA damage and cancer cell death, particularly in tumors with defects in homologous recombination repair. Irinotecan induces cytotoxicity by inhibiting topoisomerase I, resulting in DNA strand breaks during replication. The combination has shown synergistic antitumor activity preclinically and has been evaluated clinically for safety and efficacy in pediatric and adult patients with recurrent or refractory solid malignancies—including Ewing sarcoma—demonstrating feasibility, tolerability at defined doses, and preliminary clinical activity[1][4][5][6].
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