STX-478 + fulvestrant

STX-478 + fulvestrant is an investigational combination therapy being evaluated for the treatment of advanced or metastatic hormone receptor-positive (HR+) breast cancer with PI3Kα (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) mutations. **STX-478** is a next-generation, allosteric, mutant-selective, CNS-penetrant, oral small molecule inhibitor that targets PI3Kα mutations while sparing the wild-type enzyme, potentially reducing the toxicity profile compared to existing PI3K inhibitors. **Fulvestrant** is a selective estrogen receptor degrader (SERD) that acts as an antagonist of the estrogen receptor, used to block hormone signaling in ER+ tumors. The combination is designed to simultaneously inhibit oncogenic PI3Kα signaling and block estrogen-driven tumor growth, and is under investigation in multiple clinical trials as a second-line or later treatment for advanced HR+/HER2– breast cancer[1][3][5].