ASP3082 + cetuximab

**ASP3082 + cetuximab** is an investigational combination therapy for solid tumors harboring the KRAS G12D mutation. ASP3082 is a first-in-class, highly selective, intravenous proteolysis-targeting chimera (PROTAC) that induces the degradation of KRAS G12D, a frequent oncogenic driver in pancreatic, colorectal, and other cancers. By harnessing E3 ubiquitin ligase-mediated degradation, ASP3082 leads to selective proteasomal breakdown of mutant KRAS G12D protein and downstream pathway inhibition, resulting in anti-tumor activity. Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), blocking ligand binding and EGFR-mediated signaling. The combination is being clinically evaluated for enhanced efficacy, particularly in patients with colorectal cancer (CRC) harboring KRAS G12D mutations, as EGFR inhibition is a backbone for metastatic CRC therapy. The combination aims to provide a targeted approach addressing the “undruggable” nature of KRAS mutations. ASP3082 is developed by Astellas, and cetuximab is marketed by companies including Eli Lilly and Merck KGaA. Clinical investigation is ongoing in phase 1/2 for colorectal cancer and potentially other solid tumors.