AVZO-021 + ribociclib + letrozole

This combination therapy consists of **AVZO-021** (a potent, selective oral inhibitor of cyclin-dependent kinase 2 [CDK2]), **ribociclib** (an oral selective inhibitor of cyclin-dependent kinases 4 and 6 [CDK4/6]), and **letrozole** (an oral non-steroidal aromatase inhibitor that decreases estrogen synthesis). AVZO-021 is under clinical investigation primarily for hormone receptor positive (HR+) and HER2-negative (HER2-) advanced or metastatic breast cancer and cyclin E1 (CCNE1)-amplified malignancies, usually in combination with endocrine therapy[1][3][6]. This multidrug regimen is being explored to overcome or delay resistance to CDK4/6 inhibitor plus endocrine therapy, providing a potentially superior anti-tumor effect by targeting multiple points in the cell cycle control pathway in HR+/HER2- breast cancer[6]. Avenzo Therapeutics is the developer of AVZO-021, with ribociclib developed by Novartis and letrozole a long-approved generic.