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

• Zeprumetostat Tablets (Drug): 350 mg, oral, twice daily, 28-day cycle

Primary outcomes

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

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Age ≥18 years, regardless of sex;
2. Mycosis fungoides or Sézary syndrome confirmed by histopathological examination;
3. Patients with measurable disease, with or without extracutaneous involvement, and clinical stage IIB-IVB;
4. 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.);
5. 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);
6. 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;
7. ECOG performance status ≤ 2;
8. Willingness not to participate in other interventional studies during the treatment period;
9. Voluntary provision of written informed consent, understanding of the nature, purpose, and procedures of the study, and willingness to comply with the study requirements.

Exclusion Criteria:

1. Prior treatment with an EZH2 inhibitor or an EZH1/2 inhibitor;
2. Dysphagia or inability to receive oral medication due to gastrointestinal disorders;
3. History of other primary invasive malignancies that are not resolved or have been in remission for ≤ 3 years;
4. Known hypersensitivity to any medication used in the study;
5. Participation in other investigational drug clinical trials within 4 weeks prior to study initiation;
6. Concomitant use of known moderate or strong CYP3A4 or CYP3A5 inducers/inhibitors, or P-gp inhibitors;
7. History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, or history of organ transplantation;
8. Patients who have undergone major surgery within 4 weeks prior to enrollment and have not fully recovered;
9. 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;
10. 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;
11. Pregnant or lactating women, or female patients planning to become pregnant during the study;
12. History of stroke or intracranial hemorrhage within ≤ 6 months prior to the first dose of the study drug;
13. Any other condition that, in the opinion of the investigator, makes the patient unsuitable for inclusion in the study.