Table 4.
PK parameters for PF-06804103 ADC (PK parameter analysis population).
| Part 1A, PF-06804103 ADC | |||||||
|---|---|---|---|---|---|---|---|
| PF-06804103, mg/kg, Q3W | 0.15 N = 2 | 0.5 N = 2 | 1.2 N = 2 | 2.0 N = 4 | 3.0 N = 16 | 4.0 N = 15 | 5.0 N = 6 |
| Cycle 1 | |||||||
| n | 2 | 2 | 2 | 4 | 16 | 15 | 6 |
| AUCinf, μg·h/mL | 296 | 720; 969 | 2,080; 2,540 | 5,120 (11) | 9,498 (32) | 12,940 (31) | 16,550 (38) |
| AUCinf(dn), μg·h/mL/(mg/kg) | 1,960 | 1,400; 1,950 | 1,740; 2,150 | 2,566 (11) | 3,167 (32) | 3,234 (31) | 3,313 (38) |
| AUClast, μg·h/mL | 30.4; 288 | 667; 965 | 2,040; 2,500 | 5,026 (11) | 8,263 (35) | 12,290 (29) | 15,480 (39) |
| AUClast(dn), μg·h/mL/(mg/kg) | 215; 1,910 | 1,300; 1,940 | 1,700; 2,110 | 2,520 (11) | 2,748 (35) | 3,071 (29) | 3,099 (39) |
| CL, L/h | 0.0405 | 0.0516; 0.0611 | 0.0282; 0.0373 | 0.02073 (32) | 0.01970 (27) | 0.01884 (24) | 0.01975 (40) |
| C max, μg/mL | 1.96; 2.61 | 9.96; 12.6 | 16.3; 22.0 | 36.97 (24) | 71.24 (21) | 78.91 (21) | 103.1 (28) |
| C max(dn), μg/mL/(mg/kg) | 13.9; 17.3 | 19.4; 25.3 | 13.6; 18.6 | 18.50 (24) | 23.69 (21) | 19.74 (21) | 20.64 (28) |
| t 1/2, mean ± SD (d) | 4.21 | 1.75; 2.09 | 3.63; 3.67 | 3.495 ± 0.76081 | 4.257 ± 1.1289 | 5.001 ± 1.2963 | 4.962 ± 1.3623 |
| T max, median (range; h) | 1.00; 1.08 | 1.05; 3.60 | 1.00; 1.10 | 3.91 (3.67–22.9) | 3.82 (0.967–4.03) | 3.67 (0.967–24.0) | 2.42 (0.967–24.0) |
| V z, L | 5.93 | 3.13; 4.43 | 3.54; 4.74 | 2.462 (26) | 2.807 (15) | 3.165 (24) | 3.281 (25) |
| Cycle 4 | |||||||
| n | 0 | 1 | 2 | 4 | 9 | 12 | 4 |
| AUClast, μg·h/mL | — | 966 | 1,990; 2,790 | 2,970 (105) | 7,432 (31) | 10,990 (33) | 11,740 (23) |
| AUClast(dn), μg·h/mL/(mg/kg) | — | 1,880 | 1,660; 2,360 | 1,543 (109) | 2,758 (20) | 3,412 (34) | 3,491 (47) |
| AUCtau, μg·h/mL | — | 980 | 1,990; 2,800 | 4,260; 4,950 | 7,504 (28) | 10,730 (33) | 11,990 (23) |
| AUCtau(dn), μg·h/mL/(mg/kg) | — | 1,910 | 1,660; 2,370 | 2,450; 2,500 | 2,785 (19) | 3,396 (34) | 3,563 (49) |
| CL, L/h | — | 0.0449 | 0.0256; 0.0391 | 0.0196; 0.0217 | 0.02069 (28) | 0.01731 (27) | 0.01971 (49) |
| C max, μg/mL | — | 10.3 | 16.9; 29.3 | 43.00 (15) | 53.29 (29) | 76.52 (24) | 82.13 (7) |
| C max(dn), μg/mL/(mg/kg) | — | 20.0 | 14.1; 24.8 | 22.32 (20) | 19.76 (10) | 23.76 (20) | 24.43 (23) |
| Rac | — | 1.34 | 0.972; 1.12 | 0.887; 1.07 | 1.007 (20) | 1.164 (22) | 1.114 (15) |
| t 1/2, mean ± SD (d) | — | 2.34 | 2.95; 3.46 | 2.98; 3.42 | 4.177 ± 1.1648 | 5.185 ± 1.1855 | 5.278 ± 2.2199 |
| T max, median (range; h) | — | 1.00 | 0.917; 1.02 | 2.43 (1.08–3.83) | 1.10 (0.883–4.05) | 3.81 (0.967–4.17) | 4.00 (3.65–4.00) |
| V ss, L | — | 3.93 | 2.76; 4.82 | 1.94; 2.77 | 3.037 (15) | 3.106 (24) | 3.467 (24) |
Note: Values are geometric mean (geometric %CV) unless otherwise stated. Individual values are listed when there were less than 3 evaluable measurements. dn was calculated on the basis of reported actual dose (mg)/baseline body weight (kg).
Abbreviations: %CV, percentage coefficient of variation; ADC, antibody–drug conjugate; AUCinf, area under the concentration-time curve from time 0 to infinity; AUClast, area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration; AUCtau, area under the concentration-time profile from time 0 to time tau (τ), the dosing interval, where tau = 504 hours for the Q3W dosing; Cmax, maximum serum concentration; CL, clearance; dn, dose normalization; n, number of patients contributing to the summary statistics; N, total number of patients in the treatment group in the PK parameter population; PK, pharmacokinetics; Q3W, once every 3 weeks; Rac, observed accumulation ratio based on AUCtau, t1/2, elimination half-life; Tmax, time for Cmax; Vss, volume of distribution at steady state; Vz, volume of distribution based on the terminal phase.