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

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

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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 ÔëÑ3 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.

Original language	English
Article number	IJH35
Journal	Arztliche Praxis Neurologie Psychiatrie
Volume	10
Issue number	3
Early online date	23 Oct 2021
DOIs	https://doi.org/10.2217/ijh-2021-0004
Publication status	Published - 2021

Bibliographical note

Note: This work was supported by Biomarin/Medivation, National Institute for Health Research University College London Hospitals Biomedical Research Center, Janssen, AstraZeneca, and Pfizer.

Keywords

BRCA1/2 mutations
DNA damage response
Pharmacy
hematologic malignancy
poly(ADP-ribose) polymerase inhibition
short communication
talazoparib

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10.2217/ijh-2021-0004

Gaymes-T-50069-VoRFinal published version, 485 KBLicence: CC BY-NC

https://doi.org/10.2217/ijh-2021-0004

Cite this

@article{371f05995cbf49409ab7b346abed147c,

title = "A Phase I trial of talazoparib in patients with advanced hematologic malignancies",

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 {\^O}{\"e}{\~N}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.",

keywords = "BRCA1/2 mutations, DNA damage response, Pharmacy, hematologic malignancy, poly(ADP-ribose) polymerase inhibition, short communication, talazoparib",

author = "Gopal, \{Ajay K\} and Rakesh Popat and Mattison, \{Ryan J\} and Tobias Menne and Adrian Bloor and Terry Gaymes and Asim Khwaja and Mark Juckett and Ying Chen and Cotter, \{Matthew J\} and Mufti, \{Ghulam J\}",

note = "Note: This work was supported by Biomarin/Medivation, National Institute for Health Research University College London Hospitals Biomedical Research Center, Janssen, AstraZeneca, and Pfizer.",

year = "2021",

doi = "10.2217/ijh-2021-0004",

language = "English",

volume = "10",

journal = "Arztliche Praxis Neurologie Psychiatrie",

issn = "1436-2643",

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number = "3",

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T1 - A Phase I trial of talazoparib in patients with advanced hematologic malignancies

AU - Gopal, Ajay K

AU - Popat, Rakesh

AU - Mattison, Ryan J

AU - Menne, Tobias

AU - Bloor, Adrian

AU - Gaymes, Terry

AU - Khwaja, Asim

AU - Juckett, Mark

AU - Chen, Ying

AU - Cotter, Matthew J

AU - Mufti, Ghulam J

N1 - Note: This work was supported by Biomarin/Medivation, National Institute for Health Research University College London Hospitals Biomedical Research Center, Janssen, AstraZeneca, and Pfizer.

PY - 2021

Y1 - 2021

N2 - 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 ÔëÑ3 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.

AB - 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 ÔëÑ3 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.

KW - BRCA1/2 mutations

KW - DNA damage response

KW - Pharmacy

KW - hematologic malignancy

KW - poly(ADP-ribose) polymerase inhibition

KW - short communication

KW - talazoparib

U2 - 10.2217/ijh-2021-0004

DO - 10.2217/ijh-2021-0004

M3 - Article

C2 - 34840720

SN - 1436-2643

VL - 10

JO - Arztliche Praxis Neurologie Psychiatrie

JF - Arztliche Praxis Neurologie Psychiatrie

IS - 3

M1 - IJH35

ER -

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

Abstract

Bibliographical note

Keywords

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