Related Experiment Video
Updated: Nov 20, 2025
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Phase 1 study of tazemetostat in Japanese patients with relapsed or refractory B-cell lymphoma
Wataru Munakata1, Yukari Shirasugi2, Kensei Tobinai1
1Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
Background:
Tazemetostat is a selective and orally available inhibitor of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and epigenetic regulator of cellular differentiation programs. We carried out a phase I study of tazemetostat in Japanese patients with relapsed or refractory B-cell non-Hodgkin-type lymphoma (B-NHL) to evaluate its tolerability, safety, pharmacokinetics, and preliminary antitumor activity.
Methods:
Tazemetostat was given orally at a single dose of 800 mg on the first day and 800 mg twice daily (BID: total 1600 mg/d) on following days in a 28-day/cycle manner. Tazemetostat dose-limiting toxicity (DLT) was evaluated up to the end of the first treatment cycle. Archival tumor tissues were analyzed for hotspot EZH2 mutations.
Results:
As of 15 January 2018, seven patients (four follicular lymphoma [FL] and three diffuse large B-cell lymphoma [DLBCL]) were enrolled. The median age was 73 (range, 59-85) years, and the median number of prior chemotherapy regimens was three (range, one to five). No DLT was observed (one patient was not evaluable due to early disease progression). The common treatment-related adverse events (AEs) were thrombocytopenia and dysgeusia (three patients each; 42.9%). No treatment-related serious AEs were observed. The objective response rate was 57% (4/7 patients), including responses in three of four patients with FL and one of three patients with DLBCL. An EZH2 mutation was detected in one patient with FL responding to treatment.
Conclusions:
Tazemetostat at 800 mg BID showed an acceptable safety profile and promising antitumor activity in Japanese patients with relapsed or refractory B-NHL.
Insights
Tazemetostat demonstrated an acceptable safety profile and promising antitumor activity in Japanese patients with relapsed or refractory B-cell non-Hodgkin lymphoma. The study evaluated its tolerability, safety, and efficacy in this patient population.
Area of Science:
- Oncology
- Pharmacology
- Epigenetics
Background:
- Tazemetostat is an oral inhibitor of enhancer of zeste homolog 2 (EZH2), a key epigenetic regulator.
- EZH2 plays a role in cellular differentiation programs.
- Relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) presents a significant unmet need.
Purpose of the Study:
- To evaluate the tolerability and safety of tazemetostat in Japanese patients with relapsed or refractory B-NHL.
- To assess the pharmacokinetics and preliminary antitumor activity of tazemetostat.
- To investigate EZH2 mutations in relation to treatment response.
Main Methods:
- Phase I clinical study design.
- Oral administration of tazemetostat at 800 mg twice daily (BID).
- Evaluation of dose-limiting toxicity (DLT) and adverse events (AEs).
- Analysis of archival tumor tissues for EZH2 mutations.
Main Results:
- Seven patients (4 follicular lymphoma [FL], 3 diffuse large B-cell lymphoma [DLBCL]) were enrolled.
- No DLT observed; common AEs included thrombocytopenia and dysgeusia.
- Objective response rate was 57% (4/7), with responses in FL and DLBCL.
- One patient with FL and an EZH2 mutation responded to treatment.
Conclusions:
- Tazemetostat (800 mg BID) exhibits an acceptable safety profile in Japanese patients with relapsed/refractory B-NHL.
- Promising antitumor activity was observed, warranting further investigation.
- EZH2 inhibition represents a potential therapeutic strategy for B-NHL.
Related Concept Videos
01:11Clinical Trials: Overview
02:56Treatment Resistant Cancers
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...