BBO-10203 + fulvestrant + ribociclib

BBO-10203 + fulvestrant + ribociclib is an **investigational drug combination** under clinical evaluation for the treatment of hormone receptor–positive, HER2-negative advanced breast cancer with confirmed PIK3CA mutation. **BBO-10203** is a first-in-class, orally available small molecule that covalently and specifically binds to the RAS-binding domain of phosphoinositide 3-kinase alpha (PI3Kα), thereby preventing its activation by RAS family GTPases (HRAS, NRAS, KRAS) and inhibiting downstream pAKT signaling. **Fulvestrant** is an estrogen receptor antagonist that degrades the receptor and thus blocks estrogen signaling. **Ribociclib** is a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, blocking cell-cycle progression in sensitive cancers. Preclinical studies indicate that combining BBO-10203 with ER and CDK4/6 inhibition exerts synergistic antitumor effects in ER+/HER2- models, particularly with PIK3CA mutation, and the combination regimen is being evaluated in clinical trials for its safety and efficacy in this patient population[5][6].