Table 5.
AMG 232 pharmacokinetic parameters in the 240-mg dose expansion
| Characteristica | WDLPS (n = 9–10) | DDLPS (n = 6–10) | GBM (n = 6–9) | Other Solid (n = 9–16) | ER + PR+ Breast (n = 6–8) | ER + PR– Breast (n = 4) | Multiple Myeloma (n = 7–10) | Total (n = 47–67) |
|---|---|---|---|---|---|---|---|---|
| Day 1 | ||||||||
| Cmax, ng/mL | 1350 (815) | 986 (582) | 978 (630) | 1670 (858) | 1920 (1010) | 1360 (487) | 1320 (687) | 1390 (798) |
| tmax, h | 3.1 (1.1–3.1) | 2.0 (0.98–3.1) | 3.0 (1.0–3.3) | 3.0 (0.98–5.2) | 2.8 (1.0–24) | 2.1 (1.0–3.1) | 2.0 (1.0–3.1) | 3.0 (0.98–24) |
| AUC24h, ng•h/mL | 9260 (5500) | 8010 (6760) | 5360 (3650) | 10,800 (6270) | 9660 (3890) | 9430 (4480) | 8220 (4790) | 8830 (5400) |
| Day 7 | ||||||||
| Cmax, ng/mL | 1230 (803) | 1050 (660) | 988 (591) | 2200 (1400) | 1350 (587) | 1620 (923) | 1190 (605) | 1420 (961) |
| tmax, h | 3.0 (1.0–5.1) | 3.0 (1.0–3.1) | 2.8 (1.0–5.0) | 2.9 (0.92–5.0) | 2.8 (1.1–5.1) | 1.0 (1.0–3.0) | 1.1 (1.0–3.4) | 2.8 (0.92–5.1) |
| AUC24h, ng•h/mL | 15,700 (13,800) | 10,800 (9640) | 9210 (6400) | 17,200 (11,400) | 10,400 (4380) | 9960 (7830) | 8450 (3560) | 12,300 (9550) |
| CL/F, L/h | 30.6 (24.1) | 39.5 (29.0) | 41.2 (27.5) | 18.5 (9.1) | 27.6 (12.6) | 36.4 (22.8) | 33.6 (15.4) | 31.1 (20.9) |
| Vz/F, L | 389 (237) | 537 (435) | 1010 (671) | 353 (360) | 689 (529) | 814 (455) | 859 (277) | 627 (461) |
| t1/2,z, h | 11.2 (4.3) | 10.9 (4.3) | 18.5 (5.3) | 14.1 (7.6) | 15.0 (6.3) | 17.4 (6.9) | 15.4 (3.5) | 14.3 (5.8) |
| AUC24h AR | 1.62 (0.95) | 1.43 (0.72) | 1.50 (0.31) | 1.52 (0.57) | 1.01 (0.25) | 0.99 (0.43) | 1.39 (1.05) | 1.40 (0.72) |
AR, accumulation ratio (AUC24h cycle 1, day 1 / AUC24h cycle 1, day 7); AUC24h, area under the concentration-versus-time curve at 24 h; CL/F, clearance; Cmax, maximum observed serum concentration; t1/2,z, terminal elimination half-life; tmax, time to reach Cmax; Vz/F, volume of distribution
aAll data are mean (SD) except for tmax, which is median (range)