TR115 VS Investigator's Choice in Relapsed/Refractory Peripheral T/NK Cell Lymphoma

Phase 3Not Yet RecruitingNCT07639879

Tarapeutics Science Inc.180 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

180

Conditions

PTCL NK T-Cell Lymphoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

Assessed by Independent Review Committee (IRC) per Lugano 2014 criteria

Time frame: From randomization to disease progression or death from any cause, whichever occurs first, assessed up to 36 months.

Secondary Outcomes

Overall Survival (OS)

Time from randomization to death from any cause.

Time frame: From randomization to death from any cause, assessed up to 36 months.

Objective Response Rate (ORR)

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.

Time frame: Up to 36 months

Disease Control Rate (DCR)

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.

Time frame: Up to 36 months

Duration of Response (DOR)

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.

Time frame: From first documented response to disease progression or death, assessed up to 36 months.

Time to Response (TTR)

Time from randomization to first documented response (CR or PR) as assessed by IRC and investigator according to Lugano 2014 criteria.

Time frame: From randomization to first documented response, assessed up to 36 months.

Safety and Tolerability

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 frame: 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.

Population Pharmacokinetics of TR115

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.

Time frame: 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.