dalpiciclib + pyrotinib + fulvestrant

Dalpiciclib + pyrotinib + fulvestrant is an investigational, chemotherapy-sparing triplet combination regimen being evaluated for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-positive or HER2-low advanced or metastatic breast cancer. The regimen combines three distinct therapeutic mechanisms: dalpiciclib, an oral small-molecule cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor; pyrotinib, an oral, irreversible pan-HER tyrosine kinase inhibitor targeting EGFR (HER1), HER2, and HER4; and fulvestrant, an intramuscular selective estrogen receptor degrader (SERD). This combination is designed to simultaneously block estrogen receptor signaling, the CDK4/6-cyclin D pathway, and HER-family receptor signaling, thereby overcoming bypass resistance mechanisms and cross-talk between these pathways. It is being developed primarily by Jiangsu Hengrui Pharmaceuticals and is undergoing Phase II and Phase III clinical evaluation.