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

Autor:	Gopal AK; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA., Popat R; National Institute for Health Research University College London Hospitals Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK., Mattison RJ; Carbone Cancer Center, University of Wisconsin, Madison, WI, USA., Menne T; Department of Hematology, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK., Bloor A; The Christie NHS Foundation Trust, University of Manchester, Manchester, UK., Gaymes T; Department of Biomolecular Science, Kingston University, London, UK., Khwaja A; University College London Cancer Institute & University College London Hospitals NHS Foundation Trust, London, UK., Juckett M; Carbone Cancer Center, University of Wisconsin, Madison, WI, USA., Chen Y; Pfizer Inc., New York, NY, USA., Cotter MJ; Pfizer Inc., New York, NY, USA., Mufti GJ; Department of Hematology, King's College London, King's College Hospital NHS Foundation Trust, London, UK.
Jazyk:	angličtina
Zdroj:	International journal of hematologic oncology [Int J Hematol Oncol] 2021 Oct 22; Vol. 10 (3), pp. IJH35. Date of Electronic Publication: 2021 Oct 22 (Print Publication: 2021).
DOI:	10.2217/ijh-2021-0004
Abstrakt:	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). Competing Interests: Financial & competing interests disclosure This study was sponsored by Biomarin/Medivation, which was acquired by Pfizer Inc. in September 2016 (grant number not applicable). AK Gopal reports research support from Merck, Janssen, Seattle Genetics, I-Mab, IgM, Pfizer, BMS, AstraZeneca, Takeda, Spectrum, and Gilead; honoraria/consulting for Janssen, Seattle Genetics, Kite, Gilead, Amgen, Merck, Pfizer, and I-Mab. R Popat reports honoraria for Janssen, Takeda, GSK, and AbbVie; consulting for Janssen, AbbVie, and GSK; travel support from Janssen and Takeda. R Popat is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Center. T Menne reports honoraria for advisory board meetings for Kite/Gilead, Amgen, Novartis, Pfizer, Celgene, Daiichi-Sankyo, and Atara; honoraria for lectures for Kite/Gilead, Takeda, Janssen, and Roche; research funding from Janssen, AstraZeneca, and Novartis. A Khwaja reports speaker fees and consulting for AbbVie, Astellas, Jazz, Novartis, and Pfizer. Y Chen is a contractor of Pfizer. MJ Cotter is an employee of Pfizer and holds Pfizer shares. GJ Mufti reports research support from BMS/Celgene and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical writing assistance was provided by Hannah Logan, PhD, of CMC AFFINITY, McCann Health Medical Communications, and was funded by Pfizer. (© 2021 Ajay Gopal and coauthors.)
Databáze:	MEDLINE
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