Study of Tislelizumab Combined With Zeprumetostat for Adults With Relapsed or Refractory NKT-Cell Lymphoma

What this Trial Is About

Researchers are evaluating the combination of tislelizumab and zeprumetostat SHR2554 in patients with relapsed or refractory NKT-cell lymphoma who have previously received at least one asparaginase-based chemotherapy regimen, with or without radiotherapy. This multicenter, open-label phase IbII trial aims to determine the recommended phase II dose RP2D of zeprumetostat and assess the objective response rate at 12 weeks, using independent imaging review based on Lugano 2014 criteria. The study includes patients with relapsed or refractory disease, focusing on safety and efficacy outcomes. During phase Ib, participants receive tislelizumab 200 mg intravenously every three weeks combined with either 300 mg or 350 mg of oral zeprumetostat twice daily to identify the RP2D. In phase II, patients are divided into two groups based on prior exposure to PD-1 inhibitors those previously exposed or refractory Cohort-R and those without prior PD-1 inhibitor treatment Cohort-N. Phase II participants receive tislelizumab 200 mg IV every three weeks plus zeprumetostat at the RP2D. Treatment continues until disease progression, unacceptable side effects, withdrawal, loss to follow-up, death, or study end. Participants will be monitored through independent imaging at 12 weeks to measure response rates. Secondary outcomes include complete response rate, duration of response, progression-free survival, overall survival, and safety assessments of adverse events. Exploratory analyses involve biomarkers such as ctDNA, EBV-DNA, PD-L1, EZH2H3K27me3, and tumor microenvironment factors. The treatment safety period extends from consent until 28 days after the last dose, with follow-up lasting up to 36 months for some outcomes.

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