Figure 6. Effect on tumor growth and mouse survival of single-agent and combination therapy with DAC and immune checkpoint inhibitors.
(A) There is a significant increase in tumor doubling time (slowing of tumor growth) with single-agent DAC, single agent anti-VISTA, and sequential DAC followed by anti-VISTA, compared to PBS vehicle controls. The greatest inhibition of tumor growth is seen with the sequential combination therapy. Error bars indicated standard deviations. (B) Tumor doubling time is increased with single-agent DAC, and sequential DAC followed by anti-PD-1 treatment, compared to PBS vehicle controls. (C) Kaplan-Meier analyses show that combination therapy with DAC followed by anti-VISTA produces a modest but significant increase in mean survival compared to PBS (log rank ***p<0.0001), and that single-agent DAC confers a weaker benefit (log rank *p<.05). (D) Kaplan-Meier analyses show modest benefits with single agent DAC and single agent anti-PD-1 (both log rank *p<.05) and a major increase in mean survival with the DAC followed by anti-PD-1 combination treatment, (log rank ***p<0.0001) compared to PBS vehicle controls. The combination therapy was also significantly more effective than anti-PD-1 alone or DAC alone (log rank p<0.01 and log rank p<.05). Data are from treatment Paradigm I. #The PBS vehicle control arm includes 10 concurrent controls plus 3 historical controls from an identical tumor detection and mock treatment initiation procedure. The differences in mean survival between treatment arms remained statistically significant when only the concurrent controls were considered.