Table 2.
Population parameter estimates for the preclinical PK/PD model: the effect of MCLA-128 on tumor growth in JIMT-1 xenograft models
| Parameter | Units | Parameter estimates | RSE (%) | Shrinkage (%) |
|---|---|---|---|---|
| Population PD parameters in mice | ||||
| Tumor baseline value (Base) | mm3 | 177 | 6.7 | – |
| Zero order tumor growth rate (KG) | hr−1 | 0.338 | 22.2 | – |
| First order tumor dying rate (KD) | mm3/h | 0.004 | 15.9 | – |
| Production and loss of drug effect on KG (Kio) | hr−1 | 0.143 | 18.3 | – |
| MCLA-128 concentration with 50% of maximum effect on Kio (EC50) | mg/L | 2.60 | 47.7 | – |
| MCLA-128 concentration with 50% of maximum effect on KD (EC50_KD) | μg/L | 0.0102 | 25.1 | – |
| Progression factor | week−1 | 0.172 | 23 | – |
| Between-subject variability (%) | ||||
| Baseline | CV | 20.6 | 16.8 | |
| KG | CV | 55.1 | 1.10 | |
| KD | CV | 35.5 | 24.8 | |
| Residual variability | ||||
| Proportional residual error tumor compartment | CV | 25.6 | 7.4 | 5.9 |
Population PK parameters were scaled to mice to drive the tumor growth model, parameters reported in Table 1
RSE, relative standard error; CV, coefficient of variation; SD, standard deviation