A Phase 1 Mass Balance Study of 14 C-Labeled Talazoparib in Patients With Advanced Solid Tumors.

Abstract

This paper describes the pharmacokinetics (PK), mass balance, metabolic profiling, and safety of talazoparib after a single oral dose of 14 C-talazoparib in 6 patients with advanced solid tumors. Patients were aged ≥18 years, with a histologically confirmed advanced solid tumor at screening. A single 1-mg dose of talazoparib oral solution supplemented with 100µCi of 14 C-labeled talazoparib was administered. Blood, urine, and feces samples were collected at various time points and analyzed for talazoparib and 14 C radioactivity. Metabolic profiling and identification were also carried out. Mean recovery of 14 C radioactivity was 68.7% in urine and 19.7% in feces. Talazoparib was minimally metabolized. Renal excretion of unchanged talazoparib was a major route of elimination, with mean recovery of 54.6% of the administered dose, whereas fecal excretion of talazoparib was limited, with mean recovery of 13.6% of the administered dose. No major metabolites of talazoparib were identified in plasma, and no metabolites that individually represented more than 10% of the administered dose were recovered in urine or feces. The concentration-time profiles of unchanged talazoparib, total 14 C radioactivity in plasma, and total 14 C radioactivity in whole blood were similar, with a median time at peak concentrations of 30 minutes and mean half-life of 89.8, 96.2, and 77.6 hours, respectively. Talazoparib was minimally metabolized, and renal excretion of unchanged talazoparib was the major route of elimination.