Phase I Study of TAK-659, an Investigational, Dual SYK/FLT3 Inhibitor, in Patients with B-Cell Lymphoma.
Administration, Oral
Adult
Aged
Aged, 80 and over
Dose-Response Relationship, Drug
Drug Administration Schedule
Drugs, Investigational
/ administration & dosage
Female
Humans
Lymphoma, Follicular
/ drug therapy
Lymphoma, Large B-Cell, Diffuse
/ drug therapy
Male
Middle Aged
Protein Kinase Inhibitors
/ administration & dosage
Pyrimidines
/ administration & dosage
Pyrrolidinones
/ administration & dosage
Syk Kinase
/ antagonists & inhibitors
Treatment Outcome
Young Adult
fms-Like Tyrosine Kinase 3
/ antagonists & inhibitors
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 07 2020
15 07 2020
Historique:
received:
22
10
2019
revised:
11
03
2020
accepted:
17
04
2020
pubmed:
25
4
2020
medline:
3
11
2021
entrez:
25
4
2020
Statut:
ppublish
Résumé
TAK-659 is an investigational, dual SYK/FLT3 inhibitor with preclinical activity in B-cell malignancy models. This first-in-human, dose-escalation/expansion study aimed to determine the safety, tolerability, MTD/recommended phase II dose (RP2D), and preliminary efficacy of TAK-659 in relapsed/refractory solid tumors and B-cell lymphomas. Patients received continuous, once-daily oral TAK-659, 60-120 mg in 28-day cycles, until disease progression or unacceptable toxicity. The study applied an accelerated dose-escalation design to determine the MTD and RP2D. In the expansion phase, patients with lymphoma were enrolled in five disease cohorts at the MTD. Overall, 105 patients were enrolled [dose escalation, TAK-659 has single-agent activity in patients with B-cell lymphoma. Further studies of the drug in combination, including an evaluation of the biologically optimal and safest long-term dose and schedule, are warranted.
Identifiants
pubmed: 32327472
pii: 1078-0432.CCR-19-3239
doi: 10.1158/1078-0432.CCR-19-3239
doi:
Substances chimiques
Drugs, Investigational
0
Protein Kinase Inhibitors
0
Pyrimidines
0
Pyrrolidinones
0
TAK-659
0
FLT3 protein, human
EC 2.7.10.1
fms-Like Tyrosine Kinase 3
EC 2.7.10.1
SYK protein, human
EC 2.7.10.2
Syk Kinase
EC 2.7.10.2
Banques de données
ClinicalTrials.gov
['NCT02000934']
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3546-3556Informations de copyright
©2020 American Association for Cancer Research.