a Anti-tumour activity of ASP2453 in a subcutaneous KRAS G12C-mutated NCI-H1373 xenograft model (n = 5 mice per group, mean ± SEM). ****P < 0.0001, Dunnett’s multiple comparison test compared with vehicle. b Effect of ASP2453 on KRAS activation, KRAS mobility shift, p-ERK 1/2 and p-S6 in NCI-H1373 tumours at 6 h after administration of a single dose. c Pharmacodynamics of ASP2453 on KRAS-GTP, p-ERK 1/2 and p-S6 in NCI-H1373 tumours. Tumour samples were collected at 1, 2, 4, 6, 24 and 48 h after administration of a single dose (n = 3 mice per group, mean ± SEM). d Plasma and tumour concentrations of ASP2453. Plasma and tumour samples were collected at 1, 2, 4, 6, 24 and 48 h after administration of a single dose (n = 3 mice per group, mean ± SD).