Blood samples for PK analyses were collected up to 24 hours after dose on day 1 of cycle 1, before dose on days 2, 7, and 14 of cycle 1, and day 1 of cycle 2. PK parameters for dacomitinib, including the maximum concentration (Cmax), the time to Cmax (Tmax), and the area under the plasma concentration curve from 0 to 24 hours (AUC0‐24), were analyzed using a noncompartmental approach.
To assess plasma concentrations and PK parameters of carbamazepine and its metabolite, carbamazepine epoxide, following oral carbamazepine administration, trough blood samples were collected 5 min prior to the patient's oral dose on days −14, −1, and 0. On day 0, additional samples were drawn at 30- and 60-min following the first oral carbamazepine dose and then at each hour through 12 h.
Male and female rats (10/sex/gp) were given a single iv dose of AFM tartrate at 98.7 or 987 μg/kg (592 or 5,920 μg/m2, 100× or 1,000× the proposed human dose of 8 μg, respectively) on day 1 or daily iv dose on days 1 to 5 for five consecutive days at 98.7 μg/kg/day (592 μg/m2/day, 100× human dose, total dose of 493.5 μg/kg).
Gallbladder volume was assessed by ultrasound after a ≥8 hours fast at screening (within 21 days prior to randomization) and before the motesanib morning dose on days 8 and 15 of cycle 1, on day 1 of cycles 2 and 3, every 6 weeks thereafter, and at the safety follow-up (30 to 33 days after the last dose).
Blood and urine samples were collected before and 2 h after P dose on days 1, 4 and 5 and on a control day.
All patients provided written, informed consent and were randomized to receive either PLD at a dose of 30 mg/m as a 1-h intravenous infusion on day 4 and bortezomib at a dose of 1.3 mg/m as a 5-s intravenous bolus dose on days 1, 4, 8, and 11 of every 21-day cycle or bortezomib alone at a dose of 1.3 mg/m on the same dose and schedule.
In one such experiment, 30×106 Donor 1 GDTc were injected iv on days 6 and 12 post-leukemia cell injection, along with 100 IU recombinant human IL-2/mouse, plus one additional IL-2 dose on day 21 (Fig. 5b).
Drug and vehicle treatments were done by oral gavage twice daily, with each group receiving six doses in total over 4 days (1 dose late on day 0, 2 doses on days 1 and 2 and 1 dose early on day 3).
However, recovery of LVSΔ1423/1422 from the spleen after low dose challenge (similar to the LVS challenge dose) on day 2 PI was significantly lower.
In the pharmacodynamic study, four hours after the final dose on day 3, the animals were euthanized and the tumors tissues were excised and analyzed for p-ERK and p-AKT by immunohistochemical staining.
In the phase 1b study, whole blood specimens were collected twice before study inclusion (at screening day 28, re-screen); pre-dose on day 1; post-dose on days 15, 29, 50, 64, 78, 110, 134, 164, 190, 218; and early termination (when applicable).
