Table 3.
ADC and MMAE Final Model Parameters
| ADC | MMAE | |||
|---|---|---|---|---|
| Parameter | Population Mean (SE%) | %CV IIV (Shrinkage) | Population Mean (SE%) | %CV IIV (Shrinkage) |
| Clearance, L/h | 0.05 (10.3%) | 53.8 (4.2%) | 0.604 (8.7%) | 53.7 (11.2%) |
| Central volume (V1), L | 3.71 (3.2%) | 15.1 (10.9%) | 10.5 (7.1%) | 75.2 (16.3%) |
| Binding rate constant (Kd 1/h) | ― | ― | 0.00374 (12.3%) | 172.6 (13.6%) |
| Intercompartmental clearance (Q2), L/h | 0.02 (17.3%) | 63.7 (24.1%) | ― | ― |
| ― | ― | 13.1 (9.8%) | ― | |
| Peripheral volume (V2), L | 206 (16.6%) | ― | ― | ― |
| ― | ― | 22.2 (10.4%) | 63.6 (15.5%) | |
| Fraction metabolized | ― | ― | 1 FIX | ― |
| Intercompartmental clearance (Q3), L/h | 0.08 (5.0%) | ― | ― | ― |
| ADC to MMAE conversion rate (ALFM 1/h) | ― | ― | 2.68 (1.9%) | ― |
| Peripheral volume (V3), L | 5.0 (10.9%) | 48.1 (10.1%) | ― | ― |
| Lag compartment rate constant (Klag 1/h) | ― | ― | 15.3 (33.1%) | ― |
| BSA on central volume (V1) | 1.36 (8.6%) | ― | ― | ― |
| ― | ― | 1.22 (35.4%) | ― | |
| BSA on clearance | 1.66 (17.8%) | ― | ― | ― |
| ADA positive on clearance | 1.82 (1.7%) | ― | ― | ― |
| Albumin concentration on clearance | −0.90 (10.4%) | ― | ― | ― |
| Bilirubin on clearance | 0.15 (13.1%) | ― | ― | ― |
| AST on Kd | ― | ― | −0.672 (11.3%) | ― |
| BSA on Kd | ― | ― | −3.35 (26.8%) | ― |
| BSA on peripheral volume (V2), L | ― | ― | 1.81 (22.2%) | ― |
| BSA on peripheral volume (V3) | 1.15 (24.6%) | ― | ― | ― |
| Residual variability | 28.6%CV (0.9%) | ― | 35.7%CV (0.8%CV) | ― |
ADA, antidrug antibody; ADC, antibody‐drug conjugate; ALFM, rate constant to describe the decline in direct conversion of ADC to MMAE following time after dose; AST, aspartate transaminase; BSA, body surface area; CV, coefficient of variation; IIV, interindividual variability; Kd, binding rate constant; Klag, lag compartment rate constant; MMAE, monomethyl auristatin E; Q2, intercompartmental clearance from compartment 1 to compartment 2; Q3, intercompartmental clearance from compartment 2 to 3; SE, standard error; V1, central volume of distribution; V2, first peripheral volume of distribution; V3, second peripheral volume of distribution; 1 FIX, value fixed to 1.