Fig. 4: ARV-825 has single-agent antileukemic activity and improves survival in mice with T-ALL.

A 8-week-old Pten-deficient mice with T-ALL as indicated by the appearance of immature blasts in peripheral blood consider as day 0 and randomly assigned to treatment with a vehicle or ARV-825 (20 mg/kg intraperitoneally twice a week) (n = 8). B After 14 days of treatment, reduction of disease burden in ARV-825 compared to vehicle group documented as reduced immature blast in blood. C Kaplan–Meier survival curve for mice with T-ALL treated with ARV-825 or a vehicle (p = 0.0089). D Six-week-old NSG mice were implanted with D115 T-ALL PDX cells (1 × 10⁶) through the tail vein (N = 10). Leukemia engraftment was confirmed on day 8 via detection of hCD45+ cells in peripheral blood (upper panel) and randomly assigned to treatment with either ARV-825(10 mg/kg). The reduced leukemia burden in ARV-825 treated mice compare to vehicle as seen via flow cytometric analysis of hCD45 in peripheral blood on day 35(lower panel). E On day 38, reduced leukemia burden as expression of hCD45 on bone marrow and spleen in ARV-825 treated mice compare to vehicle. F Kaplan–Meier survival curve for mice with T-ALL treated with a vehicle or ARV-825 (p = 0.0042). G NSG mice were implanted with CUL76 T-ALL PDX cells and monitored for 10 days (n = 6). Peripheral blood of mice was subjected to flow cytometry analysis to check expression of hCD45 to document engraftment of leukemia and then treated with vehicle, ARV-825(5 mg/kg) or vehicle as above (upper panel). The reduced leukemia burden in ARV-825 treated mice compare to vehicle as seen via flow cytometric analysis of hCD45 in peripheral blood on day 19 (lower panel). H On day 22, reduced leukemia burden as expression of hCD45 on bone marrow and spleen in ARV-825 treated mice compare to vehicle. I Kaplan–Meier plot of the in vivo activity of ARV-825 against CUL76 PDX engrafted with NSG mice. Significance between ARV-825-treated vs. vehicle-treated mice was determined by a Mantel–Cox Rank Sum test. P values < 0.05 were considered to be significant.