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**AZD9574 + trastuzumab deruxtecan** is an investigational combination therapy under clinical development for advanced, unresectable, or metastatic solid tumors that are HER2-positive or HER2-low/ultralow, particularly in breast cancer. **AZD9574** is an orally administered, next-generation poly(ADP-ribose) polymerase inhibitor (PARPi) currently in early-phase clinical trials aimed at targeting DNA damage repair deficiencies in cancer cells[1][3][7]. **Trastuzumab deruxtecan (T-DXd, Enhertu)** is an antibody-drug conjugate (ADC) consisting of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase I inhibitor payload; it delivers cytotoxic chemotherapy directly to HER2-expressing cells[5][6]. The combination aims to exploit the synergistic effect of impaired DNA repair (from PARP inhibition) and targeted cytotoxic delivery to HER2-expressing tumor cells, seeking to enhance anti-tumor activity, particularly in HER2-positive or HER2-low breast cancers[3][7]. **AZD9574** is being developed by AstraZeneca, and **trastuzumab deruxtecan** is co-developed by Daiichi Sankyo and AstraZeneca.
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