LY3962673 — Investigational Agent
KRAS Inhibitor · Phase 1 · Eli Lilly and Company
Mechanism of Action
Orally bioavailable, highly potent and selective small-molecule inhibitor of KRAS G12D. It targets the aspartate-12 mutant form of KRAS, locking the oncoprotein in an inactive state and shutting down downstream RAS-MAPK and PI3K-AKT signaling. Because it is isoform-selective for G12D, it is not expected to inhibit KRAS G12C, other KRAS variants, NRAS, HRAS, or wild-type KRAS. KRAS G12D is the single most common KRAS mutation across human cancers, occurring in roughly 35% of pancreatic, 13% of colorectal, and 4% of non-small cell lung cancers.
Investigational Indications
- KRAS G12D-mutant pancreatic ductal adenocarcinoma (PDAC)
- KRAS G12D-mutant colorectal cancer (CRC)
- KRAS G12D-mutant non-small cell lung cancer (NSCLC)
- Other KRAS G12D-mutant advanced or metastatic solid tumors