RT Journal Article SR Electronic T1 Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers JF Cancer Discovery JO Cancer Discov FD American Association for Cancer Research SP 620 OP 629 DO 10.1158/2159-8290.CD-16-1250 VO 7 IS 6 A1 de Bono, Johann A1 Ramanathan, Ramesh K. A1 Mina, Lida A1 Chugh, Rashmi A1 Glaspy, John A1 Rafii, Saeed A1 Kaye, Stan A1 Sachdev, Jasgit A1 Heymach, John A1 Smith, David C. A1 Henshaw, Joshua W. A1 Herriott, Ashleigh A1 Patterson, Miranda A1 Curtin, Nicola J. A1 Byers, Lauren Averett A1 Wainberg, Zev A. YR 2017 UL http://cancerdiscovery.aacrjournals.org/content/7/6/620.abstract AB Talazoparib inhibits PARP catalytic activity, trapping PARP1 on damaged DNA and causing cell death in BRCA1/2-mutated cells. We evaluated talazoparib therapy in this two-part, phase I, first-in-human trial. Antitumor activity, MTD, pharmacokinetics, and pharmacodynamics of once-daily talazoparib were determined in an open-label, multicenter, dose-escalation study (NCT01286987). The MTD was 1.0 mg/day, with an elimination half-life of 50 hours. Treatment-related adverse events included fatigue (26/71 patients; 37%) and anemia (25/71 patients; 35%). Grade 3 to 4 adverse events included anemia (17/71 patients; 24%) and thrombocytopenia (13/71 patients; 18%). Sustained PARP inhibition was observed at doses ≥0.60 mg/day. At 1.0 mg/day, confirmed responses were observed in 7 of 14 (50%) and 5 of 12 (42%) patients with BRCA mutation–associated breast and ovarian cancers, respectively, and in patients with pancreatic and small cell lung cancer. Talazoparib demonstrated single-agent antitumor activity and was well tolerated in patients at the recommended dose of 1.0 mg/day.Significance: In this clinical trial, we show that talazoparib has single-agent antitumor activity and a tolerable safety profile. At its recommended phase II dose of 1.0 mg/day, confirmed responses were observed in patients with BRCA mutation–associated breast and ovarian cancers and in patients with pancreatic and small cell lung cancer. Cancer Discov; 7(6); 620–9. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 539