Antitumor activity of combination treatment with lenvatinib plus anti-PD-1 mAb or axitinib plus anti-PD-1 mAb in the RAG syngeneic tumor model. Mice bearing RAG tumors were allocated into treatment groups on day 1—when TVs were approximately 90 mm3—and were orally treated with lenvatinib at 10 mg/kg once daily or axitinib at 10 mg/kg twice daily, and were intraperitoneally injected with anti-PD-1 mAb at 200 μg/mouse twice weekly for 4 weeks. Data from two independent experiments (n = 20) were combined. A, TVs of individual mice. Black arrows, treatment period. B, Waterfall plots showing the greatest percent change of individual TVs from baseline after day 8. C, Kaplan–Meier plots of mouse survival. Top left, control, lenvatinib, anti-PD-1 mAb, and lenvatinib plus anti-PD-1 mAb treatment groups. Top right, control, axitinib, anti-PD-1 mAb, and axitinib plus anti-PD-1 mAb treatment groups. Survival (in days) was defined as the time from day 1 until the day when a mouse was euthanized or found dead. *, P < 0.05; ***, P < 0.001 vs. control group (log-rank test with Bonferroni correction); #, P < 0.05; ##, P < 0.01; ####, P < 0.0001 (log-rank test between groups). Bottom, median survival time of mice in each treatment group and HR (95% CI) compared with control group. N.R., not reached.