LY3499446 + abemaciclib

LY3499446 + abemaciclib is an investigational oral combination of two small molecule inhibitors targeting complementary pathways in cancer. LY3499446 is a selective inhibitor of **KRAS G12C**, a mutant form of the RAS protein involved in oncogenic signaling, while **abemaciclib** is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), which regulate cell cycle progression. The combination was developed for the treatment of advanced solid tumors, especially non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) with KRAS G12C mutation. The rationale for the combination is to simultaneously inhibit KRAS-driven oncogenic signaling and perturb cell cycle progression, potentially enhancing antitumor activity. Clinical development was halted due to unexpected toxicity from LY3499446[1][2][3].