Table 3.
Steady-state galunisertib pharmacokinetic parameters following multiple doses
| Galunisertib 50 mg one time per day+durvalumab 1500 mg Q4W | Galunisertib 50 mg two times per day+durvalumab 1500 mg Q4W | Galunisertib 80 mg two times per day+durvalumab 1500 mg Q4W | Galunisertib 150 mg two times per day+durvalumab 1500 mg Q4W | |
| Patients per cohort | 3 | 4 | 3 | 32 |
| PK-evaluable patients* | 3 | 2 | 3 | 25 |
| PK profiles | 6 | 3 | 6 | 38 |
| Cycle 1 profiles | 3 | 2 | 3 | 24 |
| Cycle 2 profiles | 3 | 1 | 3 | 14 |
| tmax, hours, median (range) | 0.6 (0.5–3.9) | 0.5 (0.5–0.9) | 3.8 (0.5–4.0) | 2.7 (0.5–4.0) |
| Cmax, µmol/L | 424 (70) | 260† (71) | 612 (39) | 1070 (83) |
| AUC(0-tau), µg·h/L | 1630 (32) (tau=24 hours) |
813 (68) (tau=12 hours) |
3150 (63) (tau=12 hours) |
6120 (58) (tau=12 hours) |
All PK parameters at steady state are geometric mean (CV %) unless stated otherwise.
*Patients with ≥1 profile of day 14 pre-dose sample, two post-dose samples, and 1 day 15 pre-dose (24-hour) sample.
†Should be interpreted with caution due to limited data (n=3). There is overlap between the observed Cmax ranges following galunisertib 50 mg one time per day and 50 mg two times per day administration (see online supplemental figure S2).
AUC(0-tau), area under the concentration versus time curve for the dosing interval; Cmax, maximum observed concentration; CV, coefficient of variation; PK, pharmacokinetics; Q4W, every 4 weeks; tmax, time of maximum observed concentration.