BBO-10203 + fulvestrant

**BBO-10203 + fulvestrant** is an investigational combination therapy for cancer, specifically advanced hormone receptor-positive, HER2-negative breast cancer with confirmed PIK3CA mutations. BBO-10203 is an orally available small molecule that covalently and selectively binds to the RAS-binding domain of phosphoinositide 3-kinase alpha (PI3Kα), thereby preventing its activation by HRAS, NRAS, and KRAS. This disrupts the RAS-PI3K signaling pathway, which is a known driver in multiple cancers. Fulvestrant is a selective estrogen receptor degrader (SERD) that antagonizes the estrogen receptor (ER). The combination is designed to inhibit tumor growth by blocking both PI3Kα-driven signaling and estrogen receptor signaling. In preclinical studies, BBO-10203 has shown to enhance efficacy when combined with endocrine therapy like fulvestrant, particularly in tumors with PIK3CA mutations or HER2 amplification/overexpression[1][2][3][4]. The combination is being evaluated in ongoing phase 1 clinical trials for advanced solid tumors, including but not limited to breast cancer[4][5][6].