This is a randomized, open-label, multicenter Phase III study evaluating the efficacy and safety of TR115, an EZH2 inhibitor, versus investigator's choice (chidamide, golidocitinib, mitoxantrone liposome, or gemcitabine) in patients with relapsed and/or refractory peripheral T/NK-cell lymphoma. Approximately 180 patients will be randomized in a 1:1 ratio. The primary endpoint is progression-free survival (PFS) assessed by an Independent Review Committee (IRC). The key secondary endpoint is overall survival (OS). The study is being conducted at approximately 40 to 60 centers across China.

Inclusion Criteria:

• Histologically confirmed peripheral T-cell lymphoma (PTCL), including PTCL-NOS, AITL, ALCL, or NKTCL
• Received at least one prior systemic therapy and prior exposure to at least one novel agent (e.g., chidamide, pralatrexate, brentuximab vedotin, etc.) or refractory/intolerant to such therapies
• Age ≥18 years
• ECOG performance status 0-1
• At least one measurable lesion per Lugano 2014 criteria (lymph node ≥1.5 cm in longest diameter or extranodal lesion ≥1.0 cm)
• Adequate organ function, defined as: ANC ≥1.5 × 10⁹/L, Platelets ≥100 × 10⁹/L, Hemoglobin ≥100 g/L, Total bilirubin ≤1.5 × ULN, ALT/AST ≤2.5 × ULN (≤5 × ULN if liver involvement), Creatinine clearance ≥50 mL/min (Cockcroft-Gault), LVEF ≥50%, QTcF <450 ms (male), <470 ms (female)
• Willingness to provide archival or fresh tumor tissue
• Life expectancy ≥3 months

Exclusion Criteria:

• Prior treatment with EZH2 or EZH1/2 inhibitors resulting in disease progression (intolerance permitted)
• Known central nervous system involvement of lymphoma
• Active uncontrolled infection requiring systemic therapy
• Significant or uncontrolled cardiovascular disease
• Prior allogeneic stem cell transplantation or autologous stem cell transplantation within 90 days prior to first dose
• Pregnancy or lactation, or unwillingness to use effective contraception
• Other malignancies within 5 years, except adequately treated basal cell carcinoma, squamous cell carcinoma, carcinoma in situ, or thyroid carcinoma
• Patients planned to receive mitoxantrone liposomal therapy with prior cumulative doxorubicin exposure ≥350 mg/m² (or equivalent anthracycline exposure)