Fig. 4

Adagrasib monotherapy and combination of adagrasib and abemaciclib increased animal survival in the KRASG12C/CDKN2A mutant H2122 brain tumor model. A, Schematic representation of the study design. The treatment protocol involved administering adagrasib at 75 mg/kg BID, abemaciclib at 50 mg/kg daily, or their combination via oral gavage to athymic mice with intracranially injected H2122 cell line xenografts (n = 8/group). Treatment spanned for a total of 5 weeks. B, Bioluminescence Imaging signal detection using Aura software was performed at different time points (2, 13, 24, and 40 days) following intracranial injection. C, Bioluminescence Imaging analysis was performed at day-40 time point. Comparisons between groups revealed no statistically significant differences. D, Kaplan–Meier survival analysis of all groups demonstrated that the combination and adagrasib treatment led to a statistically significant increase in survival compared with the abemaciclib alone and the vehicle groups. ^*, Padj < 0.05; ^**, Padj < 0.005; and.^***, Padj < 0.0005