NCT07502768

Tislelizumab Plus Zeprumetostat for Relapsed or Refractory NK/T-Cell Lymphoma

A Multicenter, Open-Label, Seamless Phase Ib/II Study Evaluating the Safety and Efficacy of Tislelizumab in Combination With Zeprumetostat (SHR2554) in Patients With Relapsed or Refractory NK/T-Cell Lymphoma

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 107 (estimated)
• Sponsor: Rong Tao · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multicenter, open-label, phase Ib/II study evaluating tislelizumab in combination with zeprumetostat (SHR2554) in patients with relapsed or refractory NK/T-cell lymphoma after at least one prior asparaginase-based chemotherapy-containing regimen, with or without radiotherapy. In phase Ib, two fixed dose levels of zeprumetostat in combination with tislelizumab will be evaluated to determine the recommended phase II dose (RP2D). In phase II, patients will be enrolled into 2 predefined cohorts according to prior exposure to PD-1 inhibitors to further evaluate efficacy and safety. The primary phase II endpoint is objective response rate at week 12 assessed by independent blinded imaging review according to Lugano 2014 criteria.

Detailed description

This is a multicenter, open-label, phase Ib/II clinical trial in relapsed or refractory NK/T-cell lymphoma. In phase Ib, patients with relapsed or refractory NK/T-cell lymphoma after at least 1 prior asparaginase-based chemotherapy-containing regimen will receive tislelizumab 200 mg intravenously every 3 weeks in combination with zeprumetostat at 1 of 2 dose levels: 300 mg orally twice daily or 350 mg orally twice daily. The dose-limiting toxicity observation window is 21 days. If neither dose level is excessively toxic, enrollment will continue until 12 evaluable patients are included in each arm. Dose selection for phase II will be based on dose-limiting toxicity and objective response rate at week 12 assessed by independent blinded imaging review according to Lugano 2014 criteria. If efficacy is similar, the lower dose level will be preferred. In phase II, patients will receive zeprumetostat at the RP2D plus tislelizumab 200 mg intravenously every 3 weeks. Patients will be enrolled into 2 predefined cohorts according to prior exposure to PD-1 inhibitors: Cohort-R (prior PD-1 exposed/refractory) and Cohort-N (PD-1 inhibitor-naive). Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, loss to follow-up, death, or study termination. The primary phase II endpoint is objective response rate at week 12 assessed by independent blinded imaging review according to Lugano 2014 criteria. Secondary endpoints include complete response rate, duration of response, progression-free survival, overall survival, and safety. Exploratory endpoints include the association of ctDNA and EBV-DNA dynamics, PD-L1, EZH2/H3K27me3, and tumor microenvironment biomarkers with clinical outcome.

Conditions

• Extranodal NK/T-cell Lymphoma
• NK/T-cell Lymphoma
• Relapsed or Refractory NK/T-Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Tislelizumab	Tislelizumab 200 mg administered intravenously on day 1 of each 21-day cycle.
DRUG	Zeprumetostat	Zeprumetostat (SHR2554), an oral EZH2 inhibitor, administered twice daily. In phase Ib, dose levels are 300 mg BID and 350 mg BID. In phase II, zeprumetostat is administered at the recommended phase II dose selected from phase Ib.

Timeline

• Start date: 2026-03-23
• Primary completion: 2027-12-30
• Completion: 2028-12-30
• First posted: 2026-03-31
• Last updated: 2026-03-31

Locations

1 site across 1 country: China