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Retlirafusp alfa + fluzoparib is a combination therapy consisting of retlirafusp alfa, a HER2-targeted antibody-drug conjugate (ADC), and fluzoparib (also known as fuzuloparib), a poly (ADP-ribose) polymerase (PARP) inhibitor. Retlirafusp alfa (SHR-A1811) is composed of a humanized anti-HER2 IgG1 monoclonal antibody conjugated to a potent topoisomerase I inhibitor payload via a protease-cleavable linker. It is designed to selectively deliver cytotoxic agents to HER2-expressing tumor cells, inducing DNA damage and cell death. Fluzoparib is a small molecule inhibitor of PARP1 and PARP2, which prevents the repair of single-strand DNA breaks, leading to double-strand breaks and synthetic lethality in cancer cells. The combination is primarily being investigated for the treatment of triple-negative breast cancer (TNBC), aiming to exploit the synergistic potential of ADC-mediated cytotoxicity and PARP-mediated DNA repair inhibition.
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