TABLE 1.
Definition and values of the PK/PD parameters used for the simulation study. Parameter estimates represent the fixed effects, and coefficients of variation (CV) are the square root of the diagonal of the variance–covariance matrix. They are inspired by the parameters estimated on blinatumomab (Zhu et al., 2016; Chen et al., 2019), with a modification of Imax to observe cytokine mitigation after several administrations
| Parameter | Estimate (% CV) | Unit | Description | |
|---|---|---|---|---|
| PK model | Cl | 1.36 (41.9) | L/h | Clearance |
| V | 3.4 (0) | L | Volume of distribution | |
| Emax | 3.59 · 105 (14) | pg/mL/h | Maximum cytokine release rate | |
| EC50 | 1 · 104 (0) | ng/mL | Drug exposure for half‐maximum cytokine release rate | |
| H | 0.92 (3) | Hill coefficient for cytokine release | ||
| PD model | Imax | 0.995 (0) | Maximum inhibition of cytokine release | |
| IC50 | 1.82 · 104 (12) | pg/mL· h | Cytokine exposure for half‐maximum cytokine inhibition | |
| kdeg | 0.18 (13) | h−1 | Degradation rate for cytokine | |
| K | 2.83 (36) | Priming factor for cytokine release |