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Table 5 Pharmacokinetic parameters of MK-2206 after the first dose when administered in combination therapy

From: Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors

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
  1. Abbreviations: AUC 0-48h  area under the curve from 0 to 48 hours, C max  maximum concentration, T max  time to maximum concentration, Q21 every 21 days, NA not available, SD standard deviation.
  2. aMean ± SD (coefficient of variation%).
  3. bMedian (range).
  4. cHarmonic mean ± pseudo SD.
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Journal of Hematology & Oncology

ISSN: 1756-8722

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