KRASG12C is an oncogenic driver mutation, and the most common KRAS mutation in NSCLC.1,2,3 KRASG12C occurs in 13% of patients with NSCLC, and in 1 to 3 % in patients with colorectal or other solid tumors. G12C is a point mutation, where at codon 12, glycine is substituted by a cysteine. This favors the active status of KRAS and amplifies the signal cascades, leading to oncogenesis.3
Mode of action and inhibition of KRAS G12C protein
Sotorasib, formerly AMG 510, specifically and irreversibly binds to cysteine-12 in a small pocket of the KRASG12C protein.3,4,5
Clinical Trial Programme of AMG 510 in Advanced Solid Tumors
Oral (abstract #1257) by Hong et al.
Poster (abstract 1339) by Aggarwal et al.
510 Poster discussion #3511, Hong et al., ASCO 2020