Table II.
Summary of in vivo activity of Volasertib
| Line Description | Tumor Type | Estimate of Median Time to Event | P-value | EFS T/C | Median RTV/CD45 at End of Study | Tumor Volume T/C1 | Median Group Response2 | EFS Activity3 |
|---|---|---|---|---|---|---|---|---|
| BT-29 | Rhabdoid | 31.2 | 0.091 | 1.3 | >4 | 0.91 | PD1 | Low |
| KT-14 | Rhabdoid | 25.6 | <0.0014 | 1.2 | >4 | 0.70 | PD1 | Low |
| KT-12 | Rhabdoid | > EP | <0.001 | > 2.3 | 3.1 | 0.36 | PD2 | Int |
| KT-10 | Wilms | 19.2 | 0.049 | 1.2 | >4 | 0.58 | PD1 | Low |
| KT-13 | Wilms | 30.3 | <0.001 | 2.1 | >4 | 0.26 | PD2 | Int |
| SK-NEP-1 | Ewing | 23.8 | <0.001 | 2.8 | >4 | 0.29 | PD2 | Int |
| EW5 | Ewing | 8.0 | 0.198 | 1.2 | >4 | 0.86 | PD1 | Low |
| TC-71 | Ewing | 11.5 | 0.300 | 1.2 | >4 | 0.84 | PD1 | Low |
| CHLA258 | Ewing | 20.1 | 0.168 | 1.2 | >4 | 0.79 | PD1 | Low |
| Rh10 | ALV RMS | 20.3 | 0.066 | 1.1 | >4 | 0.76 | PD1 | Low |
| Rh28 | ALV RMS | 20.1 | 0.006 | 1.5 | >4 | 0.63 | PD1 | Low |
| Rh30 | ALV RMS | 19.4 | 0.052 | 1.7 | >4 | 0.73 | PD2 | Low |
| Rh30R | ALV RMS | 36.9 | <0.001 | 3.1 | >4 | 0.31 | CR | Int |
| Rh18 | EMB RMS | 14.9 | 0.652 | 1.3 | >4 | 0.79 | PD1 | Low |
| BT-28 | Medulloblastoma | 5.9 | 0.513 | 0.9 | >4 | 1.09 | PD1 | Low |
| BT-45 | Medulloblastoma | 6.2 | 0.157 | 0.9 | >4 | 1.10 | PD1 | Low |
| BT-50 | Medulloblastoma | > EP | 0.474 | . | 1.5 | 0.38 | SD | NE |
| GBM2 | Glioblastoma | 33.7 | <0.001 | 3.5 | >4 | 0.17 | CR | Int |
| BT-39 | Glioblastoma | 12.6 | 0.843 | 1.1 | >4 | 0.59 | PD1 | Low |
| D645 | Glioblastoma | 13.0 | <0.001 | 2.1 | >4 | 0.26 | PD2 | Int |
| NB-SD | Neuroblastoma | > EP | <0.001 | > 3.8 | 1.9 | 0.08 | CR | Int |
| NB-1771 | Neuroblastoma | 16.3 | 0.006 | 2.4 | >4 | 0.47 | PD2 | Int |
| NB-1691 | Neuroblastoma | 25.4 | 0.048 | 1.7 | >4 | 0.40 | CR | Low |
| NB-EBc1 | Neuroblastoma | 13.1 | <0.001 | 2.6 | >4 | 0.22 | PD2 | Int |
| CHLA-79 | Neuroblastoma | 10.0 | 0.155 | 0.8 | >4 | 1.74 | PD1 | Low |
| NB-1643 | Neuroblastoma | 27.3 | <0.001 | 2.9 | >4 | 0.30 | SD | Int |
| OS-1 | Osteosarcoma | > EP | 0.001 | > 1.1 | 2.8 | 0.52 | PD2 | NE |
| OS-2 | Osteosarcoma | 22.2 | 0.026 | 1.2 | >4 | 0.84 | PD1 | Low |
| OS-17 | Osteosarcoma | 21.5 | 0.277 | 1.0 | >4 | 0.93 | PD1 | Low |
| OS-9 | Osteosarcoma | > EP | <0.001 | > 2.2 | 3.9 | 0.53 | PD2 | Int |
| OS-33 | Osteosarcoma | 30.6 | 0.014 | 1.4 | >4 | 0.75 | PD1 | Low |
| OS-31 | Osteosarcoma | 27.7 | <0.001 | 1.6 | >4 | 0.63 | PD2 | Low |
| ALL-2 | ALL B-precursor | 22.5 | 0.082 | 1.4 | >25 | . | PD1 | Low |
| ALL-8 | ALL T-cell | 34.8 | <0.001 | 4.9 | >25 | . | CR | Int |
| ALL-17 | ALL B-precursor | 17.1 | <0.001 | 2.4 | >25 | . | PD2 | Int |
| ALL-19 | ALL B-precursor | 20.8 | 0.379 | 2.1 | >25 | . | PD2 | Low |
Tumor Volume T/C value: Relative tumor volumes (RTV) for control (C) and treatment (T) mice were calculated at day 21 or when all mice in the control and treated groups still had measurable tumor volumes (if less than 21 days). The T/C value is the mean RTV for the treatment group divided by the mean RTV for the control group. High activity = T/C ≤ 0.15; Intermediate activity = T/C ≤ 0.45 but > 0.15; and Low activity = T/C > 0.45.
Objective response measures are described in detail in the Supplemental Response Definitions. PD1 = progressive disease with EFS T/C ≤ 1.5, and PD2 = progressive disease with EFS T/C > 1.5.
EFS T/C values = the ratio of the median time to event of the treatment group and the median time to event of the respective control group. High activity requires: a) an EFS T/C > 2; b) a significant difference in EFS distributions, and c) a net reduction in median tumor volume for animals in the treated group at the end of treatment as compared to at treatment initiation. Intermediate activity = criteria a) and b) above, but not having a net reduction in median tumor volume for treated animals at the end of the study. Low activity = EFS T/C < 2.
P< 0.05.