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

NCT07339527 | Not Yet Recruiting Phase 1

• 1 other identifier: B2025-804
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Mature T-cell and NK-cell Lymphoma

Outcome Measures

Primary Outcomes (3)

• DLT for Phase 1b

  To identify the dose-limiting toxicity

  The first cycle after administration (each cycle is 28 days)

• 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

• RP2D for phase Ib

  To identify the recommended phase 2 dose

  The first cycle after administration (each cycle is 28 days)

Secondary Outcomes (4)

• Complete response rate (CRR)

  Up to 24 months

• Duration of Response(DOR)

  Up to 4 years

• Progression-free survival(PFS)

  Up to 4 years

• Overall survival(OS)

  Up to 4 years

Study Arms (1)

Zeprumetostat Combined with Golidocitinib or Chidamide

EXPERIMENTAL

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; Drug: Golidocitinib; Drug: Chidamide

Interventions

Zeprumetostat DRUG

350mg, po, bid

Zeprumetostat Combined with Golidocitinib or Chidamide

Golidocitinib DRUG

Cohort 1: Golidocitinib: 150mg, po, qd

Zeprumetostat Combined with Golidocitinib or Chidamide

Chidamide DRUG

Cohort 2: Chidamide: 20mg, po, biw

Zeprumetostat Combined with Golidocitinib or Chidamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

MeSH Terms

Conditions

Lymphoma, T-Cell

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Qingqing Cai, MD. PhD.

CONTACT

+862087342823; caiqq@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 20, 2025
• First Posted: January 14, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: January 14, 2026

Record last verified: 2025-12