Sotorasib (AMG-510)

Description: Sotorasib (AMG-510; AMG510; Lumakras; Lumykras) is a novel, first-in-class and covalent/irreversible inhibitor of KRAS G12C that has been approved by FDA on 5/28/2021 to treat non-small-cell lung cancer (NSCLC). It specifically targets the KRAS G12C mutation, which is the most frequently mutated among the 3 subtypes of Ras proteins (KRas, NRas, HRas). KRAS gene mutations (e.g. G12C, G12V, G12D, and G13D) are present in approximately 30% of human cancers, and are most common in pancreatic cancer, lung adenocarcinoma, colorectal cancer, gall bladder cancer, thyroid cancer, and bile duct cancer. KRAS mutations are also observed in about 25% of patients with NSCLC, and some studies have indicated that KRAS mutations are a negative prognostic factor in patients with NSCLC. Recently, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations have been found to confer resistance to epidermal growth factor receptor (EGFR) targeted therapies in colorectal cancer; accordingly, the mutational status of KRAS can provide important information prior to the prescription of TKI therapy. Taken together, there is a need for new medical treatments for patients with pancreatic cancer, lung adenocarcinoma, or colorectal cancer, especially those who have been diagnosed to have such cancers characterized by a KRAS mutation, and including those who have progressed after chemotherapy.