HRS-6209 + HRS-9813 + HRS-8080

HRS-6209 + HRS-9813 + HRS-8080 is an investigational triplet combination regimen developed by Jiangsu HengRui Medicine for the treatment of advanced unresectable or metastatic breast cancer, particularly estrogen receptor (ER)-positive cases. The regimen consists of three novel small molecules: HRS-6209, a selective cyclin-dependent kinase 4 (CDK4) inhibitor; HRS-8080, an oral selective estrogen receptor degrader (SERD); and HRS-9813. HRS-6209 is designed to potently inhibit the CDK4/CyclinD complex and downstream Rb phosphorylation, inducing G1-phase cell cycle arrest while offering improved selectivity over CDK6 to potentially reduce hematological toxicities. HRS-8080 functions by degrading estrogen receptors and inhibiting their signaling activity, targeting both wild-type and mutated ER. The combination aims to enhance anti-tumor efficacy and overcome endocrine resistance by simultaneously targeting the cell cycle and the estrogen signaling pathway. It is currently being evaluated in Phase Ib/II clinical trials.