Tazemetostat for the Treatment of Relapsed/Refractory Follicular Lymphoma

Study Overview
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Brief Summary
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Treating Relapsed/Refractory Follicular Lymphoma with Tazemetostat

Detailed Description
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This is an open-label, monotherapy, Phase II Study clinical study. The objective is to evaluate the efficacy, safety, and pharmacokinetics of Tazemetostat in the treatment of patients with relapsed/refractory follicular lymphoma. It is planned to enroll 39 Chinese patients in 2 cohorts.

Official Title
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A Multicenter, Open-label, Phase II Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Tazemetostat for the Treatment of Patients With Relapsed/Refractory Follicular Lymphoma

Conditions
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Relapsed/Refractory Follicular Lymphoma With EZH2

Intervention / Treatment
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* Drug: Tazemetostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fully aware this study and signed the informed consent form in voluntary manner, and willing and able to comply with the study procedure; Age ≥18 years; Patients with histologically confirmed R/R FL (Grades 1, 2, 3a) Patients must have one measurable lesion Life expectancy ≥ 12 weeks; Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2 Adequate bone marrow function, renal function and hepatic function: Currently human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or cytomegalovirus (CMV) is inactive: Female patients of childbearing potential must agree to adopt dual contraceptive method Exclusion Criteria: Previous use of Tazemetostat or other EZH2 inhibitors; Patients with invasion of lymphoma to the central nervous system (CNS) or the pia mater; Previous bone marrow malignancies, Abnormalities associated with MDS and myeloproliferative neoplasms observed by cytogenetic testing and DNA sequencing;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: All patients will be enrolled to Cohort 1 and 2 based on the EZH2 mutations, respectively: Cohort 1: MT patients with R/R FL; planned enrollment number: 19; Cohort 2: WT patients with R/R FL; planned enrollment number: 20; Both cohorts have same dose administered: 800 mg, twice per day (BID), continuously, at a suggested interval of 12 hours between two doses.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 based on the EZH2 mutations<br>MT patients with R/R FL; planned enrollment number: 19; | Drug: Tazemetostat<br>* All patients will receive 800 mg of Tazemetostat, BID, administered in continuous 28-day therapeutic cycle<br>|
| Experimental: Cohort 2 based on the EZH2 mutations,<br>WT patients with R/R FL; planned enrollment number: 20; | Drug: Tazemetostat<br>* All patients will receive 800 mg of Tazemetostat, BID, administered in continuous 28-day therapeutic cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy of Tazemetostat in EZH2 (MT) (Cohort 1) | Objective response rate (ORR) of Cohort 1 evaluated by the Independent Review Committee (IRC) [based on the International Working Group-Non-Hodgkin's Lymphoma [IWG-NHL] (Cheson) 2007] | 22 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy of Tazemetostat in EZH2 (WT) (Cohort 2) | Overall survival (OS) of Cohort 1 and 2. OS: defined as the time from the first dose of study drug to death for any cause. | 22 months | 
| safety of Tazemetostat in EZH2 (WT) (Cohort 2) | The incidence and severity of treatment emergent adverse events (TEAEs). Occurrence of AEs (including SAEs) will be monitored based on the changes in vital signs, physical examination, 12-lead ECG and laboratory examinations. The severity of AEs will be graded based on NCI CTCAE V5.0. | 22 months | 
| Geomean maximum concentration (Cmax) of tazemetostat and its metabolite EPZ-6930 in blood | 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 and EPZ-6930 will be plotted using non-compartmental analysis and will be analyzed to determine Cmax. Cmax will be summarized as the geomean and geomean CV% for all participants. | Cycle1Day1: predose of first administration; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. Cycle1Day15: predose of first administration ; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. Cycle2Day1 and Cycle3Day1: predose of first administration. | 
| Median time to reach maximum concentration (Tmax) of tazemetostat and its metabolite EPZ-6930 in blood | 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 and EPZ-6930 will be plotted using non-compartmental analysis and will be analyzed to determine Tmax. Tmax will be summarized as the median (min, max) for all participants. | Cycle1Day 1: predose of first administration; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. Cycle1Day15: predose of first administration; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. Cycle2Day1 and Cycle3Day1: predose of first administration. | 
| Geomean area under the drug concentration-time curve (AUC) of tazemetostat and its metabolite EPZ-6930 after administration of tazemetostat | 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 and EPZ-6930 will be analyzed using a non-compartmental analysis approach to determine individual participant estimates of AUC. AUC will be summarized as the geomean and geomean CV% for all participants. | Cycle1Day1: predose of first administration; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. Cycle1Day15: predose of first administration; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose | 
| Geomean minimum observed concentration at steady-state (Cmin) of tazemetostat and its metabolite EPZ-6930 in blood | Cmin is defined as the minimum observed concentration at steady-state during one dosing interval. Cmin will be summarized as the geomean and geomean CV% for all participants. | Cycle1Day15, Cycle2Day1 and Cycle3Day1: predose of first administration |