VS-7375 + cetuximab

VS-7375 + cetuximab is a combination therapy under investigation for advanced solid tumors harboring the KRAS G12D mutation, including pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC)[1][5][7]. VS-7375 is a novel, oral, selective "ON/OFF" inhibitor of KRAS G12D, designed to inhibit both the active (GTP-bound) and inactive (GDP-bound) forms of KRAS G12D, thereby providing more comprehensive KRAS signaling blockade and improved clinical outcomes compared to inhibitors targeting only one state[1][3]. Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), blocking its activation and downstream signaling. Preclinical studies demonstrate that the combination of VS-7375 with cetuximab induces strong anti-tumor efficacy in KRAS G12D mutant cancer models, and ongoing phase 1/2a clinical trials are assessing its safety, tolerability, and efficacy[3][5][7]. The combination is being developed by Verastem Oncology, with GenFleet Therapeutics collaborating in China[2][4][7].