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

Gopal, AK; Popat, R; Mattison, RJ; Menne, T; Bloor, A; Gaymes, T; Khwaja, A; ... Mufti, GJ; + view all (2021) A Phase I trial of talazoparib in patients with advanced hematologic malignancies. International Journal of Hematologic Oncology , 10 (3) 10.2217/ijh-2021-0004. Green open access

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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).

Type: Article
Title: A Phase I trial of talazoparib in patients with advanced hematologic malignancies
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.2217/ijh-2021-0004
Publisher version: https://www.futuremedicine.com/doi/full/10.2217/ij...
Language: English
Additional information: This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: BRCA1/2 mutations, DNA damage response, hematologic malignancy, poly(ADP-ribose) polymerase inhibition, talazoparib
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10139844
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