Table 3.
Selected mean (SD) pharmacokinetic parameters for total antibody and unconjugated MMAE after DLYE5953A treatment at cycle 1
| TOTAL ANTIBODY | No. of patientsa | Cmax (ug/mL) | AUC0-inf (day*ug/mL) | t1/2 (day) | Vss (mL/kg) | CL (mL/day/kg) |
|---|---|---|---|---|---|---|
|
| ||||||
| Cohorts: 0.2 mg/kg | 3 | 3.45 (1.14) | 13.6 (6.2) | 7.05 (1.61) | 126 (39) | 16.6 (6.1) |
| 0.4 mg/kg | 3 | 7.74 (0.62) | 29.8 (3.6) | 8.38 (1.89) | 109 (13.9) | 13.6 (1.8) |
| 0.8 mg/kg | 3 | 16.1 (4.6) | 89.7 (37.1) | 13.3 (1.2) | 129 (41) | 10.1 (4.0) |
| 1.6 mg/kg | 4 | 36.9 (8.9) | 141 (37) | 4.97 (1.94) | 71.6 (27.3) | 12.0 (2.5) |
| 2.4 mg/kg | 7 | 44.1 (11.5) | 219 (69) | 7.60 (2.709) | 90.5 (20.4) | 11.9 (3.3) |
| 2.4 mg/kg MBC | 22 | 47.0 (9.7) | 258 (77) | 7.02 (2.31) | 88.0 (24.4) | 10.0 (2.7) |
| 2.4 mg/kg NSCLC | 24 | 46.4 (7.6) | 253 (101) | 7.27 (2.38) | 87.4 (20.9) | 10.9 (4.4) |
|
| ||||||
| UNCONJUGATED MMAE | No. of patientsa | Cmax (ng/mL) | AUC0-inf (day*ng/mL) | tmax( day) | ||
| Cohorts: 0.2 mg/kg | 3 | 0. 461 (0.057) | 3.18 (0.61) | 1.64 (0.57) | ||
| 0.4 mg/kg | 3 | 0.728 (0. 161) | 7.13 (NA) | 1.65 (0.57) | ||
| 0.8 mg/kg | 3 | 1.69 (1.05) | 13.4 (11.7) | 2.01 (0.05) | ||
| 1.6 mg/kg | 4 | 6.17 (3.85) | 66.6 (35.6) | 5.43 (6.95) | ||
| 2.4 mg/kg | 7 | 6.07 (2.26) | 53.1 (27) | 3.01 (2.62) | ||
| 2.4 mg/kg MBC | 14 | 4.08 (2.08) | 34.9 (18.2) | 3.10 (3.46) | ||
| 2.4 mg/kg NSCLC | 10 | 4.85 (2.44) | 36.5 (16.8) | 2.71 (2.23) | ||
a
Number of patients with at least one pharmacokinetic parameter estimated
AUC0-inf = area under the concentration−time curve from time zero extrapolated to infinite time; CL = clearance; Cmax = maximum observed plasma concentration; Vss = volume of distribution at steady state; t1/2 = terminal half-life; tmax = time to reach maximum concentration.