Table 2.
Anti-tumor Efficacy of MLN8237 in vivo
| Line description | Tumor type | Treatment groupa | Estimate of median time to event | P value (unadjusted) | EFS T/C | Median RTV/hCD45 at end of study | Tumor volume T/C | Median group response | T/C volume activity | EFS activity | Response activity |
|---|---|---|---|---|---|---|---|---|---|---|---|
| KT-10 | Wilms | B | >EP | <0.001 | >4.4 | 0.0 | 0.35 | MCR | Int | High | High |
| KT-10 | Wilms | C | 14.6 | 0.009 | 1.5 | >4 | 0.53 | PD1 | Low | Low | Low |
| KT-10 | Wilms | D | 16.0 | 0.110 | 1.7 | >4 | 0.71 | PD2 | Low | Low | Int |
| KT-10 | Wilms | E | 9.6 | 0.768 | 1.0 | >4 | 0.84 | PD1 | Low | Low | Low |
| Rh65 | ALV Rhabdomyosarcoma | B | >EP | <0.001 | >3.9 | 0.0 | 0.01 | MCR | High | High | High |
| Rh65 | ALV Rhabdomyosarcoma | C | >EP | <0.001 | >3.9 | 3.2 | 0.11 | PD2 | High | Int | Int |
| Rh65 | ALV Rhabdomyosarcoma | D | 39.3 | <0.001 | 3.7 | >4 | 0.19 | PD2 | Int | Int | Int |
| Rh65 | ALV Rhabdomyosarcoma | E | 22.9 | <0.001 | 2.1 | >4 | 0.31 | PD2 | Int | Int | Int |
| NB-SD | Neuroblastoma | B | >EP | <0.001 | >4.4 | 0.9 | 0.47 | SD | Low | High | Int |
| NB-SD | Neuroblastoma | C | 37.5 | <0.001 | 3.9 | >4 | 0.50 | PD2 | Low | Int | Int |
| NB-SD | Neuroblastoma | D | 20.9 | <0.001 | 2.2 | >4 | 0.60 | PD2 | Low | Int | Int |
| NB-SD | Neuroblastoma | E | 15.2 | <0.001 | 1.6 | >4 | 0.59 | PD1 | Low | Low | Low |
| NB-1771 | Neuroblastoma | B | >EP | <0.001 | >2.1 | 0.0 | 0.02 | MCR | High | High | High |
| NB-1771 | Neuroblastoma | C | >EP | <0.001 | >2.1 | 0.0 | 0.08 | MCR | High | High | High |
| NB-1771 | Neuroblastoma | D | >EP | <0.001 | >2.1 | 2.2 | 0.38 | PD2 | Int | Int | Int |
| NB-1771 | Neuroblastoma | E | 38.2 | <0.001 | 1.9 | >4 | 0.38 | PD2 | Int | Low | Int |
| NB-EBc1 | Neuroblastoma | B | >EP | <0.001 | >7.2 | 0.3 | 0.15 | MCR | Int | High | High |
| NB-EBc1 | Neuroblastoma | C | 17.9 | <0.001 | 3.1 | >4 | 0.22 | PD2 | Int | Int | Int |
| NB-EBc1 | Neuroblastoma | D | 11.3 | <0.001 | 2.0 | >4 | 0.44 | PD2 | Int | Low | Int |
| NB-EBc1 | Neuroblastoma | E | 9.6 | 0.010 | 1.7 | >4 | 0.57 | PD2 | Low | Low | Int |
| NB-1643 | Neuroblastoma | B | >EP | <0.001 | >2.4 | 0.0 | 0.14 | MCR | High | High | High |
| NB-1643 | Neuroblastoma | C | >EP | <0.001 | >2.4 | 0.0 | 0.30 | MCR | Int | High | High |
| NB-1643 | Neuroblastoma | D | >EP | <0.001 | >2.4 | 0.4 | 0.38 | PR | Int | High | High |
| NB-1643 | Neuroblastoma | E | 20.3 | 0.203 | 1.2 | >4 | 1.01 | PD1 | Low | Low | Low |
| NB-1382 | Neuroblastoma | B | >EP | <0.001 | >1.7 | 2.1 | 0.31 | PD2 | Int | NE | Int |
| SK-N-AS | Neuroblastoma | B | 7.6 | 0.077 | 1.4 | >4 | 0.71 | PD1 | Low | Low | Low |
| OS-1 | Osteosarcoma | B | >EP | <0.001 | >1.5 | 0.8 | 0.45 | SD | Int | NE | Int |
| OS-1 | Osteosarcoma | C | >EP | <0.001 | >1.5 | 2.0 | 0.56 | PD2 | Low | NE | Int |
| OS-1 | Osteosarcoma | D | >EP | 0.022 | >1.5 | 3.4 | 0.70 | PD2 | Low | NE | Int |
| OS-1 | Osteosarcoma | E | >EP | 0.026 | >1.5 | 3.5 | 0.75 | PD2 | Low | NE | Int |
| ALL-2 | ALL B-precursor | B | >EP | <0.001 | >3.8 | 0.3 | – | MCR | High | High | |
| ALL-2 | ALL B-precursor | C | >EP | <0.001 | >3.8 | 3.1 | – | CR | Int | High | |
| ALL-2 | ALL B-precursor | D | >EP | <0.001 | >3.8 | >25 | – | CR | Int | High | |
| ALL-2 | ALL B-precursor | E | 25.2 | <0.001 | 2.3 | >25 | – | PD2 | Int | Int | |
| ALL-8 | ALL T-cell | B | >EP | 0.002 | >3.3 | 0.2 | – | MCR | High | High | |
| ALL-8 | ALL T-cell | C | >EP | <0.001 | >3.3 | 6.2 | – | CR | Int | High | |
| ALL-8 | ALL T-cell | D | 31.6 | 0.001 | 2.5 | >25 | – | PR | Int | High | |
| ALL-8 | ALL T-cell | E | 23.0 | 0.052 | 1.8 | >25 | – | PD2 | Low | Int | |
| ALL-19 | ALL B-precursor | B | 41.8 | 0.026 | 16.8 | >25 | – | CR | Int | High | |
| ALL-19 | ALL B-precursor | C | 37.2 | 0.012 | 14.9 | >25 | – | CR | Int | High | |
| ALL-19 | ALL B-precursor | D | 22.9 | 0.041 | 9.2 | >25 | – | PD2 | Int | Int | |
| ALL-19 | ALL B-precursor | E | 2.6 | 0.742 | 1.0 | >25 | – | PD1 | Low | Low |
aTreatment groups correspond to the following doses: A controls, B 20.8 mg kg, C 10.4 mg/kg, D 5.2 mg/kg, and E 2.6 mg/kg, >EP greater than evaluation period