Figure 3.

K-476 exerts an antitumor effect in combination with anti-PD-L1 antibody. B16-derived melanoma bearing mice were used for the antitumor study and pharmacokinetics evaluation. Anti-PD-L1 antibody was intraperitoneally administered once daily on days 0, 2 and 4. A-C. The left panels show the mean tumor volume (mm³) (n = 10 mice/group). The right panels show the area under tumor growth curve (tumor AUC) of each mouse and the mean (n = 10). A. The antitumor effect of the continuous administration of K-476 with or without anti-PD-L1 antibody. K-476 was orally administered once daily on days 0-4 and 7-11. B. The antitumor effect of K-476 (25 and 50 mg/kg) with anti-PD-L1 antibody. K-476 (25 mg/kg) was administered once daily on days 0-4, 7-11 and 14-15. K-476 (50 mg/kg) was administered on days 0, 4, 7, 11 and 14. C. The antitumor effect of K-476 (50, 100, 200 and 400 mg/kg, intermittent) with anti-PD-L1 antibody. K-476 was orally administered at doses of 50, 100 and 200 mg/kg on days 0, 4, 8, 12, 16 and 20 with an anti-PD-L1 antibody. D. The plasma concentration-time profiles of K-476 in mice after a single oral administration of K-476 at doses of 10, 50, 100, 200 and 400 mg/kg.