A LYSA Phase Ib Study of Tazemetostat (EPZ-6438) plus R-CHOP in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) with Poor Prognosis Features.
Clin Cancer Res
; 26(13): 3145-3153, 2020 07 01.
Article
em En
| MEDLINE
| ID: mdl-32122924
ABSTRACT
PURPOSE:
The histone-methyl transferase EZH2, catalytic subunit of the PRC2 complex involved in transcriptional regulation, is mutated in approximately 25% of germinal center B-cell lymphomas. Aberrant proliferative dependency on EZH2 activity can be targeted by the orally available EZH2 inhibitor tazemetostat (EPZ-6438). We report the results of the phase Ib tazemetostat plus R-CHOP combination (NCT02889523), in patients 60 to 80 years of age with newly diagnosed diffuse large B-cell lymphoma. PATIENTS ANDMETHODS:
The primary objective of this dose-escalation study was to evaluate the safety of the combination and to determine the recommended phase II dose (RP2D) of tazemetostat.RESULTS:
A total of 17 patients were enrolled. During C1 and C2, two dose-limiting toxicities were observed one grade 3 constipation at 400 mg and one grade 5 pulmonary infection at 800 mg. Grade 3 or more toxicities observed in more than 10% of the patients were constipation (24%), nausea (12%), and hypokalemia (12%). Grade 3 to 4 hematologic adverse events were recorded in 8 patients (47%) neutropenia (47%), leukopenia (29%), anemia (18%), and thrombocytopenia (12%). The tazemetostat RP2D was 800 mg. No organ-oriented toxicity increased with tazemetostat dosage escalation (severity and incidence). At 800 mg, AUC and Cmax of tazemetostat were similar compared with the single-agent study (E7438-G000-101).CONCLUSIONS:
The RP2D of tazemetostat combined with R-CHOP is 800 mg twice a day. The association presents safety and PK comparable with R-CHOP alone. Preliminary efficacy data are encouraging and further investigations in phase II trial are warranted.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Linfoma Difuso de Grandes Células B
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França