Tazemetostat for the Treatment of Relapsed/Refractory Follicular Lymphoma

Phase 2

Completed

• Conditions: Relapsed/Refractory Follicular Lymphoma With EZH2
• Interventions: Drug: Tazemetostat

• Registration Number: NCT05467943
• Lead Sponsor: Hutchmed

Brief Summary

Treating Relapsed/Refractory Follicular Lymphoma with 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 Timeline

• Study First Submitted: 2022-06-28
• Study First Submitted QC: 2022-07-18
• Study First Posted: 2022-07-21
• Study Start: 2022-07-29
• Primary Completion: 2024-11-30
• Study Completion: 2024-11-30
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-21
• Last Update Posted: 2025-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1 based on the EZH2 mutations	Tazemetostat	MT patients with R/R FL; planned enrollment number: 19;
Cohort 2 based on the EZH2 mutations,	Tazemetostat	WT patients with R/R FL; planned enrollment number: 20;

Primary Outcome Measures

Name	Time	Method
efficacy of Tazemetostat in EZH2 (MT) (Cohort 1)	22 months	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\]

Secondary Outcome Measures

Name	Time	Method
Median time to reach maximum concentration (Tmax) of tazemetostat and its metabolite EPZ-6930 in blood	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.	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.
efficacy of Tazemetostat in EZH2 (WT) (Cohort 2)	22 months	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.
safety of Tazemetostat in EZH2 (WT) (Cohort 2)	22 months	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.
Geomean maximum concentration (Cmax) of tazemetostat and its metabolite EPZ-6930 in blood	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.	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.
Geomean area under the drug concentration-time curve (AUC) of tazemetostat and its metabolite EPZ-6930 after administration of tazemetostat	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	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.
Geomean minimum observed concentration at steady-state (Cmin) of tazemetostat and its metabolite EPZ-6930 in blood	Cycle1Day15, Cycle2Day1 and Cycle3Day1: predose of first administration	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.

Trial Locations

Locations (1)

Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China