Table 5.
Steady-state pharmacokinetics (day 15 of cycle 1) of WNT974, its active metabolite LHA333, and encorafenib.
| WNT974 | LHA333 | Encorafenib | |||||
|---|---|---|---|---|---|---|---|
| COMBO5 (n = 9) |
COMBO7.5 (n = 5) |
COMBO10 (n = 3) |
COMBO5 (n = 9) |
COMBO7.5 (n = 5) |
COMBO10 (n = 3) |
All cohorts (N = 17) |
|
| AUC0−t, h·ng/mL | 220 (86.4) | 384 (109) | 460 (451) | 117 (105) | 241 (63.6) | 239 (206) | 13,700 (7130) |
| AUCΤ, h·ng/mL | 227 (83.1) | 384 (109) | 542 (101) | 141 (96.7)† | 241 (63.7) | 291 (101)a | 13,800 (4940)b |
| C max, ng/mL | 51.0 (23.2) | 93.4 (55.7) | 42.9 (37.1) | 13.3 (7.48) | 25.5 (8.03) | 14.0 (12.9) | 2840 (1430) |
| T max, h | 1.00 (0.48-5.53) |
1.02 (0.47-3.00) |
4.00 (1.00-7.17) |
1.98 (0.92-6.50) |
1.95 (0.47-4.00) |
4.00 (2.00-7.17) |
1.95 (0.48-7.17) |
| t 1/2, h | 4.74 (2.17) | 5.37 (0.697) | 11.0 (9.12)a | 7.95 (2.53)c | 7.43 (1.07) | 15.0 (12.5)a | 4.29 (2.42)b |
Data are mean (SD) for AUC0−t, AUCΤ, Cmax, and t1/2 and median (range) for Tmax.
a n = 2; bn = 16; cn = 8.
Abbreviations: AUC0−t, area under the plasma concentration-time curve from time zero to infinity; AUCΤ, area under the plasma concentration-time curve during a dosing interval; Cmax, maximum plasma drug concentration; t1/2, terminal half-life; Tmax, time to Cmax.