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

Ajay K Gopal; Rakesh Popat; Ryan J Mattison; Tobias Menne; Adrian Bloor; Terry Gaymes; Asim Khwaja; Mark Juckett; Ying Chen; Matthew J Cotter; Ghulam J Mufti

doi:10.2217/ijh-2021-0004

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

Int J Hematol Oncol. 2021 Oct 22;10(3):IJH35. doi: 10.2217/ijh-2021-0004. eCollection 2021 Sep.

Authors

Ajay K Gopal¹, Rakesh Popat², Ryan J Mattison³, Tobias Menne⁴, Adrian Bloor⁵, Terry Gaymes⁶, Asim Khwaja⁷, Mark Juckett³, Ying Chen⁸, Matthew J Cotter⁸, Ghulam J Mufti⁹

Affiliations

¹ Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
² National Institute for Health Research University College London Hospitals Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK.
³ Carbone Cancer Center, University of Wisconsin, Madison, WI, USA.
⁴ Department of Hematology, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
⁵ The Christie NHS Foundation Trust, University of Manchester, Manchester, UK.
⁶ Department of Biomolecular Science, Kingston University, London, UK.
⁷ University College London Cancer Institute & University College London Hospitals NHS Foundation Trust, London, UK.
⁸ Pfizer Inc., New York, NY, USA.
⁹ Department of Hematology, King's College London, King's College Hospital NHS Foundation Trust, London, UK.

Abstract

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.

Associated data

ClinicalTrials.gov/NCT01399840