PTCL, NK T-Cell Lymphoma
Conditions
Brief summary
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.
Interventions
DRUGTR115
TR115 will be administered orally twice daily until documented disease progression, unacceptable toxicity, withdrawal of consent, death, or study discontinuation.
Investigator's choice treatment with chidamide, golidocitinib, mitoxantrone hydrochloride liposome, or gemcitabine hydrochloride administered according to the respective approved prescribing information.
Sponsors
Tarapeutics Science Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From randomization to disease progression or death from any cause, whichever occurs first, assessed up to 36 months. | Assessed by Independent Review Committee (IRC) per Lugano 2014 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Population Pharmacokinetics of TR115 | Pre-dose and approximately 2 hours (±6 minutes) post-dose on Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1, up to approximately 36 months. | Population pharmacokinetic analyses will be conducted using plasma concentration data collected from participants receiving TR115. A nonlinear mixed-effects modeling approach will be used to characterize the pharmacokinetic profile of TR115 and evaluate the effects of intrinsic and extrinsic covariates on pharmacokinetic characteristics. |
| Overall Survival (OS) | From randomization to death from any cause, assessed up to 36 months. | Time from randomization to death from any cause. |
| Objective Response Rate (ORR) | Up to 36 months | Proportion of participants achieving complete response (CR) or partial response (PR) as assessed by Independent Review Committee (IRC) and investigator according to Lugano 2014 criteria. |
| Disease Control Rate (DCR) | Up to 36 months | Proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) as assessed by IRC and investigator according to Lugano 2014 criteria. |
| Duration of Response (DOR) | From first documented response to disease progression or death, assessed up to 36 months. | Time from first documented response (CR or PR) to disease progression or death from any cause, whichever occurs first, as assessed by IRC and investigator according to Lugano 2014 criteria. |
| Safety and Tolerability | From first dose of study treatment until 30 days after the last dose, or until initiation of new anti-cancer therapy, whichever occurs first, up to approximately 36 months. | Incidence of adverse events (AEs), serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), Grade ≥3 AEs, treatment-related AEs, AEs leading to dose modification or discontinuation, and deaths, as assessed by investigators and summarized using MedDRA classification and CTCAE v6.0. |
| Time to Response (TTR) | From randomization to first documented response, assessed up to 36 months. | Time from randomization to first documented response (CR or PR) as assessed by IRC and investigator according to Lugano 2014 criteria. |
Countries
China
Contacts
CONTACTYang Shu
Outcome results
None listed