Table 3.
T-DM1 estimated PD model parameters (CV %) and derived TSC values [80% confidence intervals] for 3 CLX models in mouse (N87, BT474 and HCC-1954)
| Parameter (unit) | Description | JIMT-1 CLX (Breast) |
N87 CLX (Breast) |
BT474 CLX (Gastric) |
144580 PDX (Breast) |
HCC-1954 CLX (Breast) |
||
|---|---|---|---|---|---|---|---|---|
| Doses (mg/kg) | IV q4d × 4 | 6 | 0, 1, 3, 10 | 0, 1, 3, 10 | 6 | 0, 0.3, 1, 3 | ||
| kg, Ex (day−1) | Exponential growth rate | No response | 0.0732 (11) | 0.0575 (46) | No response | 0.0918 (8) | ||
| kg (mm3 day−1) | Linear growth rate | 37.9 (17) | 77.4 (20) | 40.7 (6) | ||||
| Vmax (mm3) | Maximum tumor volume | 4.22E+03 (18) | 5.28E+03 (23) | 3.18E+03 (27) | ||||
| τ (day) | Transduction time | 1.36 (16) | 2.4 (7) | 1 (8) | ||||
| kk, max (day−1) | Maximum kill rate | 0.405 (38) | 1.38 (91) | 0.319 (7) | ||||
| kc50 (µg mL−1) | Concentration at half maximal kill rate | 131 (48) | 311 (110) | 8.63 (10) | ||||
| n | – | 1 (-) | 1.01 (4) | 1.5 (-) | ||||
| ψ | – | 20 (-) | 20 (-) | 20 (-) | ||||
| Omega kg,Ex | 0.47 (-) | 2.26 (15) | 0.371 (-) | |||||
| Omega kg | 0.781 (-) | 0.917 (16) | 0.274 (-) | |||||
| Additive error | 66.8 (6) | 30 (-) | 14.4 (10) | |||||
| Proportional error | 0.0727 (12) | 0.157 (5) | 0.0754 (8) | |||||
| Condition number | 250 | 9E+05 | 27 | |||||
|
TSC (µg mL−1) [80% CI] |
Tumor static concentration |
29 [13, 67] |
14 [2.4, 57] |
4.7 [4.0, 5.6] |
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