ASP3082, a First-in-class novel KRAS G12D degrader, exhibits remarkable anti-tumor activity in KRAS G12D mutated cancer models

Background: KRAS is one of the most frequently mutated oncogenes in various cancers. Among KRAS mutations, KRAS G12D is the most frequent driver mutation and is found in approximately 34% of pancreatic ductal adenocarcinoma (PDAC), 10% to 12% of colorectal cancer, 4% of lung adenocarcinoma and also in a subset of other solid tumors. However, there is no direct KRAS G12D-targeted inhibitors used in the clinical setting. Here, we identified ASP3082, a novel KRAS G12D degrader with high potency and selectivity.