Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial.
Adult
Aged
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Benzamides
/ administration & dosage
Biphenyl Compounds
Enhancer of Zeste Homolog 2 Protein
/ genetics
Female
Humans
Lymphoma, Follicular
/ drug therapy
Male
Middle Aged
Morpholines
Mutation
/ genetics
Neoplasm Recurrence, Local
/ drug therapy
Progression-Free Survival
Pyridones
/ administration & dosage
Treatment Outcome
Journal
The Lancet. Oncology
ISSN: 1474-5488
Titre abrégé: Lancet Oncol
Pays: England
ID NLM: 100957246
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
21
05
2020
revised:
28
07
2020
accepted:
30
07
2020
pubmed:
10
10
2020
medline:
26
11
2020
entrez:
9
10
2020
Statut:
ppublish
Résumé
Activating mutations of EZH2, an epigenetic regulator, are present in approximately 20% of patients with follicular lymphoma. We investigated the activity and safety of tazemetostat, a first-in-class, oral EZH2 inhibitor, in patients with follicular lymphoma. This study was an open-label, single-arm, phase 2 trial done at 38 clinics or hospitals in France, the UK, Australia, Canada, Poland, Italy, Ukraine, Germany, and the USA. Eligible patients were adults (≥18 years) with histologically confirmed follicular lymphoma (grade 1, 2, 3a, or 3b) that had relapsed or was refractory to two or more systemic therapies, had an Eastern Cooperative Oncology Group performance status of 0-2, and had sufficient tumour tissue for central testing of EZH2 mutation status. Patients were categorised by EZH2 status: mutant (EZH2 Between July 9, 2015, and May 24, 2019, 99 patients (45 in the EZH2 Tazemetostat monotherapy showed clinically meaningful, durable responses and was generally well tolerated in heavily pretreated patients with relapsed or refractory follicular lymphoma. Tazemetostat is a novel treatment for patients with follicular lymphoma. Epizyme.
Sections du résumé
BACKGROUND
Activating mutations of EZH2, an epigenetic regulator, are present in approximately 20% of patients with follicular lymphoma. We investigated the activity and safety of tazemetostat, a first-in-class, oral EZH2 inhibitor, in patients with follicular lymphoma.
METHODS
This study was an open-label, single-arm, phase 2 trial done at 38 clinics or hospitals in France, the UK, Australia, Canada, Poland, Italy, Ukraine, Germany, and the USA. Eligible patients were adults (≥18 years) with histologically confirmed follicular lymphoma (grade 1, 2, 3a, or 3b) that had relapsed or was refractory to two or more systemic therapies, had an Eastern Cooperative Oncology Group performance status of 0-2, and had sufficient tumour tissue for central testing of EZH2 mutation status. Patients were categorised by EZH2 status: mutant (EZH2
FINDINGS
Between July 9, 2015, and May 24, 2019, 99 patients (45 in the EZH2
INTERPRETATION
Tazemetostat monotherapy showed clinically meaningful, durable responses and was generally well tolerated in heavily pretreated patients with relapsed or refractory follicular lymphoma. Tazemetostat is a novel treatment for patients with follicular lymphoma.
FUNDING
Epizyme.
Identifiants
pubmed: 33035457
pii: S1470-2045(20)30441-1
doi: 10.1016/S1470-2045(20)30441-1
pmc: PMC8427481
mid: NIHMS1730591
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Benzamides
0
Biphenyl Compounds
0
Morpholines
0
Pyridones
0
EZH2 protein, human
EC 2.1.1.43
Enhancer of Zeste Homolog 2 Protein
EC 2.1.1.43
tazemetostat
Q40W93WPE1
Banques de données
ClinicalTrials.gov
['NCT01897571']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1433-1442Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
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