Phase 1
N=7
A Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT03009344 ↗Enrolled (actual)
7
Serious AEs
28.6%
Results posted
Nov 2022
Primary outcome: Primary: Number of Participants With Dose-limiting Toxicities (DLTs) — 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Tazemetostat (Drug)
- Age
- Adult, Older Adult · 20+ yrs
- Sex
- All
- Sponsor
- Eisai Co., Ltd.
- Primary completion
- Jul 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-limiting Toxicities (DLTs) |
— | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
7; 2 | — |
| SECONDARY Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 |
988; 790 | — |
| SECONDARY Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387 |
1.97; 1.97 | — |
| SECONDARY AUC(0-12 Hours): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose of Tazemetostat and Its Metabolite ER-897387 |
4080; 4500 | — |
| SECONDARY AUC(0-t Hours): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Tazemetostat and Its Metabolite ER-897387 |
5180; 6540 | — |
| SECONDARY AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387 |
5220; 6570 | — |
| SECONDARY Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387 |
0.0925; 0.0794 | — |
| SECONDARY T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387 |
7.76; 4.10; 8.68; 3.55 | — |
| SECONDARY CL/F: Apparent Total Body Clearance of Tazemetostat |
153 | — |
| SECONDARY Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat |
1660; 1170 | — |
| SECONDARY MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387 |
8.25; 10.7 | — |
| SECONDARY AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387 |
4220; 10200 | — |
| SECONDARY Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 |
351; 852 | — |
| SECONDARY Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 |
1170; 1800 | — |
| SECONDARY Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 |
88.4; 293 | — |
| SECONDARY PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387 |
303; 171 | — |
| SECONDARY Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387 |
1.05; 1.07 | — |
| SECONDARY CLss/F: Apparent Total Body Clearance of Tazemetostat at Steady State |
190 | — |
| SECONDARY Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387 |
1.19; 2.28 | — |
| SECONDARY Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387 |
1.04; 2.27 | — |
| SECONDARY Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387 |
0.809; 1.56 | — |
| SECONDARY Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine |
15.1; 6.81 | — |
| SECONDARY Fe: Fraction of Tazemetostat Dose Excreted in Urine |
1.89; 0.852 | — |
| SECONDARY CLR: Renal Clearance of Tazemetostat |
2.62; 1.62 | — |
| SECONDARY Percentage of Participants With Objective Response |
57.1 | — |
Summary
This is a multicenter, single-arm, open-label, Phase 1 study to assess the tolerability, safety, pharmacokinetics, and preliminary anti-tumor activity of tazemetostat in participants with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).
Eligibility Criteria
Inclusion Criteria
- Participants with histological diagnosis of B-cell non-Hodgkin's lymphoma
- Participant who has measurable disease
- Participant who had previous therapy with systemic chemotherapy and/or antibody therapy
- Participant who had progressive disease (PD) or did not have a response (complete response [CR] or partial response [PR]) in previous systemic therapy, or relapsed or progressed after previous systemic therapy
- Participant with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Participant with life expectancy of ≥3 months from starting study drug administration
- Participant with adequate renal, bone marrow, and liver function
- Participant with left ventricular ejection fraction (LVEF) > 50%
- Male and female participant ≥20 years of age at the time of informed consent
- Participant who has provided written consent to participate in the study
Exclusion Criteria
- Participant with prior exposure to EZH2 inhibitor
- Participant with a history or a presence of central nerves invasion
- Participant with allogeneic stem cell transplantation
- Participant with medical need for the continued use of potent or moderate inhibitors of CYP3A or P-gp, or potent or moderate inducer of CYP3A (including St. John's wort).
- Participant with significant cardiovascular impairment
- Participant with prolongation of corrected QT interval using Fridericia's formula (QTcF) to > 480 milliseconds (msec)
- Participant with venous thrombosis or pulmonary embolism within the last 3 months before starting study drug
- Participant with complications of hepatic cirrhosis, interstitial pneumonia, or pulmonary fibrosis
- Participant with active infection requiring systemic therapy
- Women of childbearing potential or man of impregnate potential who don't agree to use a medically effective method for contraception for periods from before informed consent to during the clinical study and 30 days later from last administration of study drug
- Woman who are pregnant or breastfeeding
- Participant who were deemed as inappropriate to participate in the study by the investigator or sub-investigator
Data sourced from ClinicalTrials.gov (NCT03009344). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.