Pharmacokinetics, safety, and antitumor activity of talazoparib monotherapy in Chinese patients with advanced solid tumors

AbstractTalazoparib, a poly(ADP-ribose) polymerase inhibitor, has demonstrated efficacy in the treatment of advanced breast and prostate cancers in Western populations. This open-label, phase 1 study investigated the pharmacokinetics, safety, and antitumor activity of talazoparib monotherapy in Chinese patients with advanced solid tumors. Molecularly unselected patients ( ≥18 years) with advanced solid tumors resistant to standard therapy received talazoparib (oral, 1 mg once daily). Primary endpoint was characterization of single-dose and steady-state pharmacokinetics. Secondary endpoints evaluated safety, unconfirmed objective response rate (ORR), and duration of response. The safety population comprised 15 Chinese patients (median [range] age 53.0 [31.0–72.0] years). Single-dose median time to first occurrence of maximum observed concentration was 1.9 h; concentrations then declined with a mean terminal half-life (t1/2) of 67 h. Following multiple dosing, median Tmax was approximately 1.85 h with steady state generally achieved by Day 21. Treatment-related treatment-emergent adverse events (TEAEs) occurred in 86.7% (13/15) of patients (grade 3, 20.0%; grade 4, 13.3%). Two patients (13.3%) experienced serious treatment-related TEAEs. ORR (investigator-assessed) was 6.7% (95% CI: 0.2 –31.9); one patient (6.7%) had a partial response. In patients with measurable disease at baseline, the ORR was 9.1% (1/11; 95% CI: 0.2–41.3; duration of response: 114 days); stable dise...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research