AMG-510, also known as sotorasib (trade name Lumakras), is a targeted oncology drug approved by the FDA in 2021 for the treatment of adult patients with non-small cell lung cancer (NSCLC) whose tumors harbor the KRAS G12C mutation and who have received at least one prior systemic therapy. This mutation occurs in approximately 13% of NSCLC cases and has been challenging to target therapeutically. Sotorasib covalently binds to the inactive GDP-bound form of KRAS G12C, locking it in an inactive state and preventing downstream signaling that promotes uncontrolled cell proliferation. As a first-in-class KRAS G12C inhibitor, it represents a breakthrough in precision medicine for KRAS-driven cancers.

Clinical trials, including the CodeBreaK 100 study, demonstrated an objective response rate of about 37% in pretreated NSCLC patients, with durable responses and manageable side effects. It is also under investigation for other KRAS G12C-mutated cancers, such as colorectal and pancreatic cancer. Sotorasib offers a valuable option for patients refractory to standard treatments like chemotherapy and immunotherapy.