A Prospective Clinical Study of Zeprumetosta in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma

NCT07854639 | Not Yet Recruiting Phase 2

• 1 other identifier: 2026R0321-0003
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with relapsed or refractory cutaneous T-cell lymphoma (R/R CTCL) face a poor prognosis and limited therapeutic options. Advanced or relapsed disease yields a 5-year overall survival rate of \<50%. Real-world data show that third-line therapy achieves an ORR of only 45-50% with a median PFS of 1.2 years. Chemotherapy remains dominant (43.1% in the third-line) but offers limited, transient efficacy (median time to next treatment: 4 months) and severe toxicities, leaving a critical unmet need for safe, highly specific targeted therapies. Epigenetic dysregulation is central to CTCL pathogenesis, particularly aberrations in the histone methyltransferase EZH2. As the catalytic subunit of PRC2, EZH2 mediates H3K27me3 to repress target gene transcription. In CTCL, EZH2 frequently undergoes copy number amplification or gain-of-function mutations to drive tumor progression. Targeting EZH2 demonstrates high tumor specificity; EZH2 inhibitors like tazemetostat and valemetostat are already approved for epithelioid sarcoma, follicular lymphoma, and peripheral T-cell lymphoma (PTCL). Preclinically, EZH2 is specifically overexpressed in neoplastic CTCL T cells, and EZH2 inhibitors dose-dependently suppress CTCL cell/tumor growth. Given shared pathogenic mechanisms, PTCL data provide strong reference for CTCL. Valemetostat achieved an ORR of 43.7% and median PFS of 5.5 months in R/R PTCL. Zeprumetostat demonstrated superior efficacy (ORR 61%, median PFS 11.1 months) with a favorable safety profile, leading to its 2025 approval in China for R/R PTCL. Therefore, this single-arm, prospective trial evaluates zeprumetostat in R/R CTCL. Given that CTCL shares essential pathogenetic and epigenetic features with PTCL, and leveraging zeprumetostat's established approval in PTCL, this study represents a rational and mechanistically justified therapeutic expansion rather than an unsupported off-label application.

Conditions

Cutaneous T-Cell Lymphoma/Mycosis Fungoides/Sézary Syndrome

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate maintained for at least 4 months (ORR4)

  The percentage of patients achieving a complete response (CR) or partial response (PR) that is maintained for at least 4 months.

  From baseline until disease progression, death, or start of new anticancer therapy, assessed up to 24 treatment cycles (approximately 22-24 months).

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Patients receive EZH2 inhibitor Zeprumetostat Tablets monotherapy

Drug: Zeprumetostat Tablets

Interventions

Zeprumetostat Tablets DRUG

350 mg, oral, twice daily, 28-day cycle

Experimental Arm

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years, regardless of sex;
• Mycosis fungoides or Sézary syndrome confirmed by histopathological examination;
• Patients with measurable disease, with or without extracutaneous involvement, and clinical stage IIB-IVB;
• Patients with no response or relapse after remission following at least one line of systemic therapy (including total-skin electron-beam irradiation, bexarotene, retinoids, interferons, extracorporeal photopheresis, methotrexate, chidamide, etc.);
• Adequate major organ function, meeting the following criteria: a) Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN) in patients without liver metastasis; b) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; c) Creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance (Ccr) ≥ 50 mL/min (calculated by the Cockcroft-Gault formula);
• Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelet count (PLT) ≥ 80 × 10\^9/L, and hemoglobin (HGB) ≥ 90 g/L;
• ECOG performance status ≤ 2;
• Willingness not to participate in other interventional studies during the treatment period;
• Voluntary provision of written informed consent, understanding of the nature, purpose, and procedures of the study, and willingness to comply with the study requirements.

You may not qualify if:

• Prior treatment with an EZH2 inhibitor or an EZH1/2 inhibitor;
• Dysphagia or inability to receive oral medication due to gastrointestinal disorders;
• History of other primary invasive malignancies that are not resolved or have been in remission for ≤ 3 years;
• Known hypersensitivity to any medication used in the study;
• Participation in other investigational drug clinical trials within 4 weeks prior to study initiation;
• Concomitant use of known moderate or strong CYP3A4 or CYP3A5 inducers/inhibitors, or P-gp inhibitors;
• History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, or history of organ transplantation;
• Patients who have undergone major surgery within 4 weeks prior to enrollment and have not fully recovered;
• Chronic respiratory disease requiring continuous oxygen therapy; history of clinically significant renal, neurological, psychiatric, endocrine, metabolic, immune, hepatic (decompensated cirrhosis Child-Pugh class B or C), or cardiovascular diseases; or any other disease that, in the investigator's judgment, may adversely affect the patient's participation in this study;
• Active, uncontrolled infections, including but not limited to: active hepatitis B (defined as positive HBsAg AND HBV DNA ≥ 2000 IU/mL AND ALT ≥ 2 × ULN, with drug-induced or other causes of hepatitis excluded), hepatitis C (defined as positive anti-HCV antibody AND positive HCV RNA), human immunodeficiency virus (HIV) infection, or positive syphilis-specific antibody test;
• Pregnant or lactating women, or female patients planning to become pregnant during the study;
• History of stroke or intracranial hemorrhage within ≤ 6 months prior to the first dose of the study drug;

Sponsors & Collaborators

• Peking University First Hospital: lead
• Jiangsu Hengrui Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; 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

Wang Yang

CONTACT

+86 18610381256; yangwang_dr@bjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician

Model Details: Single-arm, open-label, Single-stage design. Sample size calculation was based on Clopper-Pearson exact confidence interval method for the primary endpoint objective response rate (ORR)

Study Record Dates

• First Submitted: September 27, 2026
• First Posted: October 2, 2026
• Study Start (Estimated): October 31, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): May 30, 2028
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: De-identified IPD and supporting documents will become available 12 months after the publication of the primary study results and will remain accessible indefinitely to eligible researchers upon approved application.
• Access Criteria: Qualifed researchers may submit a formal research proposal and data use agreementto the study principal investigator. Proposals wil be reviewed for scientific validity prior to data access approval.

Locations

CN (1)