Table 5 Pharmacokinetic parameters of MK-2206 after the first dose when administered in combination therapy
Treatment arm | MK-2206 dosing schedule | Number of patients | AUC0-48h, nM•ha | Cmax, nMa | Tmax, hb | t1/2, hc | |
|---|---|---|---|---|---|---|---|
1 | Carboplatin AUC 6 Paclitaxel 200 mg/m2 | 45 mg QOD | 6 | 1630 ± 496 (30.4) | 57.7 ± 13.8 (23.9) | 4.0 (4.0–6.0) | NA |
60 mg QOD | 8 | 2700 ± 619 (23.0) | 88.3 ± 24.2 (27.4) | 8.0 (6.0–10.0) | NA | ||
90 mg Q3W | 5 | 4130 ± 1520 (36.6) | 144 ± 57.0 (39.6) | 6.0 (4.0–10.0) | 79.5 ± 17.3 | ||
135 mg Q3W | 6 | 7600 ± 1280 (15.3) | 255 ± 50.9 (6.8) | 8.0 (6.0–10.0) | 73.0 ± 20.0 | ||
200 mg Q3W | 5 | 9800 ± 2550 (25.9) | 458 ± 268 (58.5) | 4.0 (4.0–10.0) | 74.7 ± 13.4 | ||
2 | Docetaxel 75 mg/m2 | 45 mg QOD | 5 | 1320 ± 395 (30.0) | 42.9 ± 13.3 (30.9) | 6.0 (4.0–10.0) | NA |
Docetaxel 60 mg/m2 | 90 mg Q3W | 3 | 3000 ± 1250 (41.7) | 106 ± 42.5 (40.2) | 4.0 (4.0–10.0) | 105.4 ± 15.0 | |
135 mg Q3W | 3 | 8090 ± 542 (6.7) | 278 ± 35.5 (12.8) | 6.0 (4.0–10.0) | 106.1 ± 32.7 | ||
200 mg Q3W | 4 | 7690 ± 1550 (20.1) | 287 ± 67.6 (23.5) | 6.0 (4.0–6.0) | 86.9 ± 11.5 | ||
3 | Erlotinib 100 mg | 45 mg QOD | 9 | 1460 ± 417 (28.6) | 48.8 ± 11.2 (23.0) | 6.0 (4.0–10.0) | NA |
135 mg QW | 6 | 6420 ± 2760 (42.9) | 212 ± 75.9 (35.8) | 6.0 (2.0–6.0) | 60.6 ± 6.6 | ||
Erlotinib 150 mg QD | 45 mg QOD | 4 | 2110 ± 637 (30.2) | 65.6 ± 29.3 (44.6) | 7.0 (4.0–24.0) | NA | |
135 mg QW | 6 | 6560 ± 2650 (40.2) | 244 ± 84.2 (34.5) | 4.0 (4.0–10.0) | 50.2 ± 10.3 | ||