vepdegestrant + ribociclib

**Vepdegestrant + ribociclib** is an investigational oral combination therapy composed of vepdegestrant, a potent PROteolysis TArgeting Chimera (PROTAC) estrogen receptor degrader, and ribociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. Vepdegestrant induces proteasome-mediated degradation of estrogen receptor, blocking estrogen signaling and potentially leading to inhibition of ER+ breast cancer cell proliferation and survival. Ribociclib inhibits CDK4 and CDK6, preventing cell cycle progression from G1 to S phase in actively dividing tumor cells. The combination is targeted towards estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. Preclinical and early clinical studies suggest synergistic antitumor activity when these agents are used together, particularly in patients whose disease has progressed after prior endocrine or CDK4/6 inhibitor therapies[3][5][7].