SHR-A1811 + fulvestrant + HS-10352

SHR-A1811 + fulvestrant + HS-10352 is an investigational combination therapy for advanced breast cancer, particularly in hormone receptor-positive (HR+), HER2-negative subtypes. The regimen combines three agents with distinct mechanisms: - **SHR-A1811** is a third-generation antibody-drug conjugate (ADC) targeting human epidermal growth factor receptor 2 (HER2). It consists of an anti-HER2 antibody (trastuzumab backbone), a cleavable linker, and a topoisomerase I inhibitor payload. SHR-A1811 delivers cytotoxic activity directly to HER2-expressing or mutated tumor cells[4][3][7]. - **Fulvestrant** is a selective estrogen receptor degrader (SERD) that binds to the estrogen receptor and accelerates its degradation, thereby inhibiting estrogen signaling in HR+ breast cancer. - **HS-10352** is a novel, highly selective phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitor. It potently inhibits PI3Kα with high selectivity over other PI3K isoforms and shows antitumor activity especially in tumors harboring PIK3CA mutations[6][10]. This combination aims to simultaneously target HER2-driven signaling, block estrogen-mediated proliferation, and inhibit the PI3K pathway—a key driver of resistance in HR+/HER2-negative breast cancers.