AVZO-021 + abemaciclib + letrozole

AVZO-021 + abemaciclib + letrozole is an investigational oral combination therapy aimed at treating hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. - **AVZO-021** is a selective cyclin-dependent kinase 2 (CDK2) inhibitor being developed by Avenzo Therapeutics for advanced solid tumors, especially HR+/HER2- breast cancer and cyclin E1 (CCNE1)-amplified malignancies[3][5][1]. - **Abemaciclib** is a selective inhibitor of cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6), approved for metastatic breast cancer in combination with aromatase inhibitors such as letrozole[6][2]. - **Letrozole** is a nonsteroidal aromatase inhibitor used for endocrine therapy in breast cancer, blocking estrogen biosynthesis. This combination is designed to target two distinct cell cycle kinases (CDK2, CDK4/6) and estrogen biosynthesis, providing broader cell cycle arrest and endocrine sensitivity in resistant breast cancer subtypes. AVZO-021 is in phase 1/2 clinical trials in combination regimens for breast cancer, with combination cohorts including other endocrine therapies[1][5][7]. Primary indication: advanced hormone receptor-positive, HER2-negative breast cancer.