A Phase 1 Study of Tazemetostat in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Sponsor

Eisai Co., Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT03009344

Collaborator

(none)

Enrollment

Locations

Arm

40.5

Actual Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma	Drug: tazemetostat	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of Tazemetostat in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Actual Study Start Date :

Jan 23, 2017

Actual Primary Completion Date :

Jun 8, 2020

Actual Study Completion Date :

Jun 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: tazemetostat 800 mg Participants will receive oral tazemetostat at a starting dose of 800 milligrams (mg) as a single dose (Cycle 0) and 800 mg twice a day as continuous dosing (Cycle 1 and later).	Drug: tazemetostat tazemetostat tablets

Arm

Intervention/Treatment

Experimental: tazemetostat 800 mg

Participants will receive oral tazemetostat at a starting dose of 800 milligrams (mg) as a single dose (Cycle 0) and 800 mg twice a day as continuous dosing (Cycle 1 and later).

Drug: tazemetostat

tazemetostat tablets

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicity (DLT) of tazemetostat during Cycles 0 and 1 [up to 31 days]
A DLT is defined as a toxicity related to study drug and can be categorized as a hematological, a non-hematological, or a medication compliance toxicity. The tolerability of tazemetostat will be determined based on the incidence of DLTs in Cycles 0 and 1.

Secondary Outcome Measures

Objective response rate (ORR) based on The Lugano Classification (CT-Based Response) [From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination, up to approximately 2 years]
Preliminary anti-tumor activity will be defined by "The Lugano Classification (CT-Based Response)." ORR is defined as the proportion of participants who have a Best Overall Response (BOR) of complete response (CR) or partial response (PR).
Mean maximum concentration (Cmax) of tazemetostat in blood [Cycle (C) 0, Day (D) 1: predose; 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 hours postdose. C1D3 and C1D8: predose of first administration (PoFA). C1D15: PoFA; 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose. C1D22 and C2D1: PoFA]
Cmax is defined as the maximum observed concentration that a drug achieves in a test area of the body after the drug has been administered. Plasma concentration-time profiles of tazemetostat will be plotted using non-compartmental analysis and will be analyzed to determine Cmax. Plasma concentration-time profiles will be summarized as the mean and standard deviation for all participants.
Mean time to reach maximum concentration (Tmax) of tazemetostat in blood [Cycle (C) 0, Day (D) 1: predose; 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 hours postdose. C1D3 and C1D8: predose of first administration (PoFA). C1D15: PoFA; 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose. C1D22 and C2D1: PoFA]
Tmax is defined as the time from dosing to reach the maximum observed concentration a drug achieves in a specified compartment or test area of the body after the drug has been administered. Plasma concentration-time profiles of tazemetostat will be plotted using non-compartmental analysis and will be analyzed to determine Tmax. Tmax will be summarized as the mean and standard deviation for all participants.
Mean area under the drug concentration-time curve (AUC) after first administration of tazemetostat in blood [Cycle 0, Day 1: predose; 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 hours postdose]
AUC represents the total drug exposure over a defined period of time. AUC will be calculated using the linear trapezoidal rule. Plasma concentrations of tazemetostat will be analyzed using a non-compartmental analysis approach to determine individual participant estimates of AUC.
Mean area under the drug concentration-time curve (AUC) after repeated administration of tazemetostat in blood [Cycle 1, Day 15: predose of first administration; 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose]
AUC represents the total drug exposure over a defined period of time. AUC will be calculated using the linear trapezoidal rule. Plasma concentrations of tazemetostat will be analyzed using a non-compartmental analysis approach to determine individual participant estimates of AUC.
Mean maximum concentration (Cmax) of ER-897387 in blood [Cycle (C) 0, Day (D) 1: predose; 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 hours postdose. C1D3 and C1D8: predose of first administration (PoFA). C1D15: PoFA; 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose. C1D22 and C2D1: PoFA]
Cmax is defined as the maximum observed concentration that ER-897387 achieves in blood after the drug has been administrated. Plasma concentration-time profiles of ER-897387 in blood will be plotted using a non-compartmental analysis. Cmax will be summarized as the mean and standard deviation for all participants.
Mean time to reach maximum concentration (Tmax) of ER-897387 in blood [Cycle (C) 0, Day (D) 1: predose; 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 hours postdose. C1D3 and C1D8: predose of first administration (PoFA). C1D15: PoFA; 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose. C1D22 and C2D1: PoFA]
Tmax is defined as the time from dosing to reach the maximum observed concentration a drug achieves in blood after the drug has been administered. Plasma concentration-time profiles of ER-897387 will be plotted using a non-compartmental analysis, and plasma concentrations of ER-897387 will be analyzed to determine Tmax. Tmax will be summarized as the mean and standard deviation for all participants.
Mean area under the drug concentration-time curve (AUC) after first administration of ER-897387 in blood [Cycle 0, Day 1: predose; 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 hours postdose]
AUC represents the total drug exposure over a defined period of time. AUC will be calculated using the linear trapezoidal rule. Plasma concentrations of ER-897387 will be analyzed using a non-compartmental analysis approach to determine individual participant estimates of AUC.
Mean area under the drug concentration-time curve (AUC) after repeated administration of ER-897387 in blood [Cycle 1, Day 15: predose of first administration; 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose]
AUC represents the total drug exposure over a defined period of time. AUC will be calculated using the linear trapezoidal rule. Plasma concentrations of ER-897387 will be analyzed using a non-compartmental analysis approach to determine individual participant estimates of AUC.
Number of participants with any serious adverse event and number of participants with any non-serious adverse event [For each participant, from the first participant first dose until 30 days after the last dose (up to approximately 2 years)]
An adverse event is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A serious adverse event is defined as any adverse event occurring at any dose that results in any of the following outcomes: results in death; is life threatening; results in inpatient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life function; results in a congenital anomaly/birth defect; or can be defined as any other important medical event.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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