RLY-2608 + fulvestrant + palbociclib

RLY-2608 + fulvestrant + palbociclib is an investigational, oral combination therapy being studied primarily for hormone receptor positive, HER2-negative, PIK3CA-mutant advanced or metastatic breast cancer. RLY-2608 is a **pan-mutant and isoform-selective PI3K alpha inhibitor** designed to target mutant **PIK3CA** with higher specificity and reduced toxicity compared to broad PI3K inhibitors. Fulvestrant is a selective estrogen receptor degrader (SERD) that antagonizes and promotes degradation of the estrogen receptor. Palbociclib is a small molecule inhibitor of **cyclin-dependent kinases 4 and 6 (CDK4/6)**, blocking cell cycle progression. The combination aims to provide synergistic inhibition of key oncogenic drivers in HR+ breast cancer, particularly in tumors with PIK3CA mutations[1][2][3][5].