Figure 3. Co-treatment with venetoclax and GDC-0980 exhibits potent in vivo anti-AML activity.

NOD/SCID-γ mice were inoculated with 3 × 10⁶ luciferase-expressing MV4-11 cells via tail vein injection. 1 week later, mice were treated with regimens consisting of oral administration of venetoclax, GDC-0980, or taselisib once every day, 6 days a week as follow. (A) Mice were treated with venetoclax (80 mg/kg), GDC-0980 (5 mg/kg for 2 weeks, then 10 mg/kg until day 55) alone or in combination, and AML progression was monitored by the IVIS 200 imaging system. (B) Survival analysis of mice using Kaplan-Meier survival plot. These studies involved 5–6 mice/condition; combined treatment significantly prolonged mouse survival compared to either agent alone (P = 0.0248, and P = 0.0057 for combination versus GDC-0980 and venetoclax respectively, log-rank test). (C) Mice (8 mice/condition) were treated with venetoclax (80 mg/kg) and/or taselisib (2.5 mg/kg), and subjected to IVIS 200 imaging. (D) Kaplan-Meier survival analysis. Venetoclax/taselisib significantly prolonged mouse survival compared to either agent alone (P = 0.0113, and P = 0.0392 for combination versus taselisib and venetoclax respectively, log-rank test). * indicate mouse accidental death; these mice were excluded from survival analysis. (E) NOD/SCID-γ mice were inoculated with primary AML blasts (5 × 10⁶ cells) isolated from 2 patients with AML. 2 weeks later, mice were treated with venetoclax (80 mg/kg) and/or GDC-0980 (5 mg/kg) po qd 6 days/week for 3 weeks. Mice were left untreated for additional 3 months after which they were sacrificed and the percentages of HCD45⁺ cells in the bone marrow were assessed. Each dot represents an individual mouse (n = 5 – 6 per group). The means of different groups are statistically different for both patients AML1; P = 0.0013; AML2; P = 0.0051; One-way ANOVA.