Tazemetostat for the Treatment of Relapsed/Refractory Follicular Lymphoma

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

Treating Relapsed/Refractory Follicular Lymphoma with Tazemetostat

Study Overview

• Status: Completed
• Conditions: Relapsed/Refractory Follicular Lymphoma With EZH2
• Intervention / Treatment: Drug: Tazemetostat

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Shanghai Cancer center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Fully aware this study and signed the informed consent form in voluntary manner, and willing and able to comply with the study procedure;
2. Age ≥18 years;
3. Patients with histologically confirmed R/R FL (Grades 1, 2, 3a)
4. Patients must have one measurable lesion
5. Life expectancy ≥ 12 weeks;
6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
7. Adequate bone marrow function, renal function and hepatic function:
8. Currently human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or cytomegalovirus (CMV) is inactive:
9. Female patients of childbearing potential must agree to adopt dual contraceptive method

Exclusion Criteria:

1. Previous use of Tazemetostat or other EZH2 inhibitors;
2. Patients with invasion of lymphoma to the central nervous system (CNS) or the pia mater;
3. Previous bone marrow malignancies,
4. Abnormalities associated with MDS and myeloproliferative neoplasms observed by cytogenetic testing and DNA sequencing;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hutchmed
• Investigators: Principal Investigator: Junning Cao, MD, Shanghai Cancer center

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2022
• Primary Completion (Actual): November 30, 2024
• Study Completion (Actual): November 30, 2024

Study Registration Dates

• First Submitted: June 28, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular
• Other Study ID Numbers: 2021-TAZ-00CH1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No