Pre-clinical efficacy of trastuzumab deruxtecan plus sotorasib in KRAS^G12C-mutant non-small cell lung cancer and exploratory HER2 profiling in human tumors

KRAS^G12Cinhibitors such as adagrasib and sotorasib have shown promise in treating KRAS^G12C-mutant non-small cell lung cancer (NSCLC), but treatment resistance remains a major challenge. In this study, we investigated the therapeutic potential of combining trastuzumab deruxtecan (T-DXd), an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC), with sotorasib in KRAS^G12C-mutant NSCLC xenografts and evaluated HER2 expression in NSCLC patient samples.