A Phase Ib/IIa Study of the Pan-BET Inhibitor ZEN-3694 in Combination with Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer.
Aged
Aged, 80 and over
Androstenes
/ administration & dosage
Antineoplastic Agents
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Benzamides
/ administration & dosage
Disease-Free Survival
Drug Resistance, Neoplasm
/ drug effects
Humans
Male
Middle Aged
Neoplasm Metastasis
Nitriles
/ administration & dosage
Phenylthiohydantoin
/ administration & dosage
Progression-Free Survival
Prostatic Neoplasms, Castration-Resistant
/ drug therapy
Receptors, Androgen
/ genetics
Treatment Outcome
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 10 2020
15 10 2020
Historique:
received:
04
05
2020
revised:
24
06
2020
accepted:
17
07
2020
pubmed:
23
7
2020
medline:
24
11
2021
entrez:
23
7
2020
Statut:
ppublish
Résumé
ZEN-3694 is a bromodomain extraterminal inhibitor (BETi) with activity in androgen-signaling inhibitor (ASI)-resistant models. The safety and efficacy of ZEN-3694 plus enzalutamide was evaluated in a phase Ib/IIa study in metastatic castration-resistant prostate cancer (mCRPC). Patients had progressive mCRPC with prior resistance to abiraterone and/or enzalutamide. 3+3 dose escalation was followed by dose expansion in parallel cohorts (ZEN-3694 at 48 and 96 mg orally once daily, respectively). Seventy-five patients were enrolled ( ZEN-3694 plus enzalutamide demonstrated acceptable tolerability and potential efficacy in patients with ASI-resistant mCRPC. Further prospective study is warranted including in mCRPC harboring low AR transcriptional activity.
Identifiants
pubmed: 32694156
pii: 1078-0432.CCR-20-1707
doi: 10.1158/1078-0432.CCR-20-1707
pmc: PMC7572827
mid: NIHMS1614596
doi:
Substances chimiques
Androstenes
0
Antineoplastic Agents
0
Benzamides
0
Nitriles
0
Receptors, Androgen
0
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
abiraterone
G819A456D0
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5338-5347Subventions
Organisme : NCI NIH HHS
ID : R01 CA251245
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097186
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA092629
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA186786
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224079
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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