Pharmacokinetic drug-drug interaction assessment of peptibody trebananib in combination with chemotherapies.

Abstract

To provide the first evaluation of pharmacokinetic (PK) drug-drug interactions (DDIs) between trebananib and chemotherapies across tumor types. PK data of trebananib and chemotherapies (paclitaxel, carboplatin, pegylated liposomal doxorubicin, topotecan, capecitabine, lapatinib, 5-FU, irinotecan, or docetaxel) were collected from trials of ovarian cancer, metastatic breast cancer, colorectal carcinoma, and mixed solid tumor. A dedicated PK DDI study of trebananib and paclitaxel in patients with mixed solid tumors was also conducted. The geometric least squares mean (GLSM) ratios and corresponding 90% confidence intervals (CI) of C max and AUC were estimated for DDI evaluations. In the PK DDI study of trebananib and paclitaxel, the GLSM ratio (90% CI) was 1.17 (1.10-1.25) for paclitaxel AUC and 1.30 (1.15-1.48) for paclitaxel C max. The GLSM ratio (90% CI) for the effect of paclitaxel on trebananib PK was 0.92 (0.87-0.97) for trebananib AUC and 0.98 (0.92-1.05) for trebananib C max. In the remaining studies, the GLSM ratios (90% CI) of C max and AUC generally ranged from 0.8 to 1.25 or exhibited less than twofold PK variabilities across chemotherapeutic agents. No dose-dependent DDIs were evident. No PK DDI was deemed clinically meaningful between trebananib and the tested chemotherapeutic agents to warrant dose adjustments.