abemaciclib + LY3023414

Abemaciclib + LY3023414 is an investigational **oral combination therapy** under clinical evaluation for advanced and metastatic cancers, especially in hormone receptor-positive (HR+), HER2-negative metastatic breast cancer and pretreated metastatic pancreatic ductal adenocarcinoma (PDAC)[1][2][3][7]. **Abemaciclib** is a selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, which blocks cell cycle progression in cancer cells, arresting tumor growth. **LY3023414** is a dual PI3K/mTOR inhibitor that suppresses two key signaling pathways involved in tumor cell proliferation and survival[2][7]. The combination targets dysregulated cell cycle and PI3K/mTOR signaling in tumors. Studies have shown manageable safety profiles, though dose-limiting toxicities were common, and antitumor activity was observed in specific patient subgroups (e.g., 66.7% objective response rate in a cohort with fulvestrant in metastatic breast cancer)[1][5][7]. The combination remains investigational; no recommended Phase 2 dose has been established for this combination in breast cancer due to dose-limiting toxicities[1][5]. **Developer:** Eli Lilly.

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