Cutaneous T-Cell Lymphoma/Mycosis Fungoides/Sézary SyndromePhase 2NCT07854639
A Prospective Clinical Study of Zeprumetosta in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma
A Phase 2 study testing Zeprumetostat Tablets in people with Cutaneous T-Cell Lymphoma/Mycosis Fungoides/Sézary Syndrome, run by Peking University First Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous T-Cell Lymphoma/Mycosis Fungoides/Sézary Syndrome
- What is being tested?
- Zeprumetostat Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteChina
- Study dates
- 31 Oct 2026to 30 May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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;
- Any other condition that, in the opinion of the investigator, makes the patient unsuitable for inclusion in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Peking University First Hospital
Beijing, Beijing Municipality, 100034
About this study
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.
Read more
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.
- Being tested
- Zeprumetostat Tablets
- Medical subject headings
- Lymphoma, T-Cell, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zeprumetostat TabletsDrug
350 mg, oral, twice daily, 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Patients receive EZH2 inhibitor Zeprumetostat Tablets monotherapy Receives: Drug: Zeprumetostat Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline until disease progression, death, or start of new anticancer therapy, assessed up to 24 treatment cycles (approximately 22-24 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2026
- Study start31 Oct 2026 (estimated)
- Primary completion1 Dec 2027 (estimated)
- Study completion30 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous T-Cell Lymphoma/Mycosis Fungoides/Sézary SyndromeStudies of the same condition, open and under way.
- More trials run by Peking University First HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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)
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University First Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Jiangsu Hengrui Pharmaceutical Co., Ltd.
- Responsible party
- Principal investigator, Yang WANG, Peking University First Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07854639
- Sponsor's protocol ID
- 2026R0321-0003
- Status last verified
- Sep 2026
- First submitted
- 27 Sep 2026
- Last updated
- 2 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identifed individual participant data including baseline characteristics, efficacy and safety outcome data willbe shared after study completion and primary publication.
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Clinical Study of Zeprumetosta in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT07854639
- Acronym / sponsor ID
- 2026R0321-0003
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- Peking University First HospitalUniversity, hospital or other
- Collaborators
- Jiangsu Hengrui Pharmaceutical Co., Ltd.
- Study start
- 31 Oct 2026 (estimated)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 30 May 2028 (estimated)
- First posted
- 2 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Drug: Zeprumetostat TabletsPatients receive EZH2 inhibitor Zeprumetostat Tablets monotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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);
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zeprumetostat Tablets350 mg, oral, twice daily, 28-day cycle | Drug | Experimental Arm |
Primary outcome
Objective Response Rate maintained for at least 4 months (ORR4)
Time frame: From baseline until disease progression, death, or start of new anticancer therapy, assessed up to 24 treatment cycles (approximately 22-24 months).
The percentage of patients achieving a complete response (CR) or partial response (PR) that is maintained for at least 4 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Individual participant dataSharing planned: Yes. De-identifed individual participant data including baseline characteristics, efficacy and safety outcome data willbe shared after study completion and primary publication.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zeprumetostat Tablets in people with Cutaneous T-Cell Lymphoma/Mycosis Fungoides/Sézary Syndrome, run by Peking University First Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wang Yang (+86 18610381256, yangwang_dr@bjmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate maintained for at least 4 months (ORR4) (time frame: From baseline until disease progression, death, or start of new anticancer therapy, assessed up to 24 treatment cycles (approximately 22-24 months).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026; AzTrials last refreshed its copy on 8 Nov 2026.