LY3023414 + abemaciclib + fulvestrant

LY3023414 + abemaciclib + fulvestrant is a three-drug investigational combination for treating advanced or metastatic hormone receptor-positive (HR+), HER2-negative breast cancer. - **LY3023414** is an oral, selective, dual inhibitor of PI3K (class I isoforms), mTOR, and DNA-dependent protein kinase (DNA-PK). - **Abemaciclib** is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), approved as Verzenio, that blocks cell cycle progression from G1 to S phase. - **Fulvestrant** is a selective estrogen receptor degrader (SERD) that antagonizes and degrades the estrogen receptor, inhibiting estrogen signaling. This combination is designed to target multiple complementary pathways critical to tumor proliferation and endocrine resistance. In early phase studies, the combination showed preliminary antitumor activity but dose-limiting toxicities prevented establishment of a recommended phase 2 dose[1][4][10].