EZH2 Inhibitor Zeprumetostat in Combination Therapy for Patients With Relapsed or Refractory Mature T-cell and NK-cell Lymphomas

An Open-label, Multicenter, Exploratory Clinical Study of the EZH2 Inhibitor Zeprumetostat in Combination Therapy for Patients With Relapsed or Refractory Mature T-cell and NK-cell Lymphomas.

This is a prospective, multicenter, open-label, phase Ib/II clinical study to evaluate the safety and efficacy of EZH2 inhibitor Zeprumetostat in combination therapy for patients with relapsed or refractory mature T-cell and NK-cell lymphomas.

Study Overview

• Status: Not yet recruiting
• Conditions: Mature T-cell and NK-cell Lymphoma
• Intervention / Treatment: Drug: Zeprumetostat; Drug: Golidocitinib; Drug: Chidamide

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Qingqing Cai, MD. PhD.; Phone Number: +862087342823; Email: caiqq@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntarily participate in the clinical study; fully understand and be informed about the study and sign the Informed Consent Form (ICF); willing to comply with and capable of completing all trial procedures;
• Age ≥ 18 years
• Pathologically confirmed mature T-cell and NK-cell lymphomas.
• Using the Lugano 2014 criteria, the patient must have at least one measurable or evaluable lesion
• Participants must have experienced disease progression, treatment failure, or intolerance following standard therapy. Patients with ALCL are required to have previously received anti-CD30-targeted therapy, while patients with NKTCL must have previously been treated with pegaspargase or L-asparaginase.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate organ and bone marrow function

Exclusion Criteria:

• Lymphoma involvement in the central nervous system or meninges
• Active infections
• Prior treatment with an EZH2 inhibitor or an EZH1/2 dual inhibitor that was discontinued due to intolerance to toxicity;
• For patients enrolled in Cohort 1, prior treatment with a JAK inhibitor that was discontinued due to intolerance to toxicity;
• For patients enrolled in Cohort 2, prior treatment with an HDAC inhibitor that was discontinued due to intolerance to toxicity.
• History of Human Immunodeficiency Virus (HIV) infection and/or Acquired Immunodeficiency Syndrome (AIDS).
• Patients with mental disorders or those unable to provide informed consent
• Any other condition deemed by the investigator to be unsuitable for study enrollment;
• Pregnant or breastfeeding women, and subjects of childbearing potential who are unwilling to use contraception;
• Individuals with a known hypersensitivity to any of the investigational drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Zeprumetostat Combined with Golidocitinib or Chidamide; In Cohort 1, patients will receive Zeprumetostat in combination with Golidocitinib, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Golidocitinib at the RP2D dose level for an extension study. In Cohort 2, patients will receive Zeprumetostat in combination with Chidamide, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Chidamide at the RP2D dose level for an extension study.

Drug: Zeprumetostat; 350mg, po, bid; Drug: Golidocitinib; Cohort 1: Golidocitinib: 150mg, po, qd; Drug: Chidamide; Cohort 2: Chidamide: 20mg, po, biw

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate(ORR) for Phase 2	The proportion of patients who achieve complete remission (CR) or partial remission (PR) as the best response.	Up to 24 months
DLT for Phase 1b	To identify the dose-limiting toxicity	The first cycle after administration (each cycle is 28 days)
RP2D for phase Ib	To identify the recommended phase 2 dose	The first cycle after administration (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response(DOR)	To investigate the preliminary anti-tumor efficacy	Up to 4 years
Progression-free survival(PFS)	To investigate the preliminary anti-tumor efficacy	Up to 4 years
Overall survival(OS)	To investigate the preliminary anti-tumor efficacy	Up to 4 years
Complete response rate (CRR)	Defined as the proportion of patients who achieve complete remission as the best response	Up to 24 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: December 20, 2025
• First Submitted That Met QC Criteria: January 4, 2026
• First Posted (Actual): January 14, 2026

Study Record Updates

• Last Update Posted (Actual): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 4, 2026
• Last Verified: December 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; Hemic and Lymphatic Diseases; Lymphoma, T-Cell; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide
• Other Study ID Numbers: B2025-804

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No