Table 3 Pharmacokinetic parameters of M2698 in the monotherapy and combination cohorts on day 15
From: Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancer
Dose, mg | n | Cmax, ng/mL GeoMean (GeoCV%) | tmax, hours median (range) | AUC0–τ, ng∙h/mL Geo mean (GeoCV%) | Accumulation ratio (Cmax) Geo mean (GeoCV%) |
|---|---|---|---|---|---|
M2698 monotherapy | |||||
15 | 3 | 136 (16.8) | 3.00 (2.97–7.50) | 2540 (6.0) | 2.57 (73.6) |
30 | 3 | 279 (14.5) | 4.30 (1.93–6.02) | 5410 (17.8) | 3.19 (41.2) |
60 | 5 | 566 (48.5) | 5.07 (3.03–7.62) | 10,000 (47.7) | 3.03 (60.4) |
75 | 4 | 533 (47.5) | 4.05 (4.03–5.12) | 9440 (39.6) | 3.02 (3.2) |
110 | 3 | 831 (43.3) | 6.05 (3.00–6.07) | 15,500 (46.8) | 3.38 (55.6) |
160 | 5 | 1300 (45.1) | 4.08 (1.93–6.00) | 23,700 (43.7) | 2.40 (36.8) |
200 | 3 | 1520 (100.8) | 3.77 (3.50–4.05) | 28,400 (91.6) | 3.21 (63.5) |
240 | 7 | 1920 (48.5) | 4.00 (2.95–6.10) | 31,300 (55.8) | 2.51 (77.8) |
320 | 6 | 2110 (39.6) | 5.48 (3.57–6.08) | 39,700 (52.3) | 2.12 (67.9) |
380 | 2 | 2490 (9.4) | 2.50 (2.00–3.00) | 41,400 (34.5) | 2.20 (97.9) |
Combination with tamoxifen | |||||
80 | 2 | 819 (50.9) | 4.5 (4.00–5.00) | 16,000 (44.7) | 2.31 (20.6) |
160 | 5 | 1270 (48.3) | 3.33 (2.95–5.58) | 22,000 (42.9) | 1.98 (26.6) |
200 | 6 | 1380 (31.3) | 3.98 (3.07–10.0) | 27,000 (29.3) | 3.47 (65.7) |
240 | 4 | 1110 (39.9) | 3.15 (2.13–4.00) | 20,600 (41.7) | 1.7 (40.9) |
Combination with trastuzumab | |||||
80 | 3 | 405 (23.7) | 3.07 (2.03–5.58) | 7400 (34.3) | 2.00 (26.1) |
160 | 7 | 2560 (52.8) | 5.88 (3.05–8.08) | 47,200 (49.3) | 2.73 (31.5) |