A Phase I trial of talazoparib in patients with advanced hematologic malignancies

Gopal, Ajay K, Popat, Rakesh, Mattison, Ryan J, Menne, Tobias, Bloor, Adrian, Gaymes, Terry, Khwaja, Asim, Juckett, Mark, Chen, Ying, Cotter, Matthew J and Mufti, Ghulam J (2021) A Phase I trial of talazoparib in patients with advanced hematologic malignancies. International Journal of Hematologic Oncology, 10(3), IJH35. ISSN (print) 2045-1393


Aim: The objective of this study was to establish the maximum tolerated dose (MTD), safety, pharmacokinetics, and anti-leukemic activity of talazoparib. Patients & methods: This Phase I, two-cohort, dose-escalation trial evaluated talazoparib monotherapy in advanced hematologic malignancies (cohort 1: acute myeloid leukemia/myelodysplastic syndrome; cohort 2: chronic lymphocytic leukemia/mantle cell lymphoma). Results: Thirty-three (cohort 1: n = 25; cohort 2: n = 8) patients received talazoparib (0.1-2.0 mg once daily). The MTD was exceeded at 2.0 mg/day in cohort 1 and at 0.9 mg/day in cohort 2. Grade ≥3 adverse events were primarily hematologic. Eighteen (54.5%) patients reported stable disease. Conclusion: Talazoparib is relatively well tolerated in hematologic malignancies, with a similar MTD as in solid tumors, and shows preliminary anti leukemic activity.Clinical trial registration: NCT01399840 (ClinicalTrials.gov). Keywords: BRCA1/2 mutations; DNA damage response; hematologic malignancy; poly(ADP-ribose) polymerase inhibition; talazoparib.

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