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A combination therapy consisting of AVZO-021, ribociclib, and fulvestrant, under clinical investigation for advanced hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer in patients who may have cyclin E1 (CCNE1) amplification or have progressed after prior endocrine therapy with or without CDK4/6 inhibitors. AVZO-021 is an investigational, potent, and selective oral cyclin-dependent kinase 2 (CDK2) inhibitor. Ribociclib is an oral selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). Fulvestrant is a selective estrogen receptor degrader (SERD) that binds to and accelerates degradation of the estrogen receptor. The rationale for combining these agents is to target key nodes of the cell cycle and hormone signaling pathways that drive resistance in HR+/HER2- advanced breast cancer.
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