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

NCT07502768 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: SHCA-NKT-2601
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Tislelizumab; Zeprumetostat; EZH2 inhibitor; PD-1 inhibitor; NKTCL

Outcome Measures

Primary Outcomes (2)

• Recommended Phase II Dose (RP2D) of zeprumetostat in combination with tislelizumab

  Determination of the recommended phase II dose based on dose-limiting toxicities during the first 21 days and objective response rate at week 12.

  During phase Ib, up to 12 weeks

• Objective Response Rate (ORR) at Week 12

  Objective response rate assessed by independent blinded imaging review according to Lugano 2014 criteria during phase II.

  Week 12

Secondary Outcomes (5)

• Complete Response Rate (CRR)

  12 weeks

• Duration of Response (DOR)

  From first documented CR or PR until first documented disease progression, relapse, or death, up to 36 months

• Progression-Free Survival (PFS)

  From first dose until first documented disease progression or death from any cause, up to 36 months

• Overall Survival (OS)

  From first dose until death from any cause, up to 36 months

• Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-Related Adverse Events (irAEs)

  From signing of informed consent through 28 days after the last dose of study treatment

Other Outcomes (1)

• Objective Response Rate (ORR) in Predefined Biomarker Subgroups

  12 weeks

Study Arms (4)

Phase Ib Dose Level A

EXPERIMENTAL

Tislelizumab 200 mg IV every 3 weeks plus zeprumetostat 300 mg orally twice daily.

Drug: Tislelizumab; Drug: Zeprumetostat

Phase Ib Dose Level B

EXPERIMENTAL

Tislelizumab 200 mg IV every 3 weeks plus zeprumetostat 350 mg orally twice daily.

Drug: Tislelizumab; Drug: Zeprumetostat

Phase II Cohort-R (Prior PD-1 Exposed/Refractory)

EXPERIMENTAL

Tislelizumab 200 mg IV every 3 weeks plus zeprumetostat at the RP2D in patients previously exposed or refractory to PD-1 inhibitor therapy.

Drug: Tislelizumab; Drug: Zeprumetostat

Phase II Cohort-N (PD-1 Inhibitor-Naive)

EXPERIMENTAL

Tislelizumab 200 mg IV every 3 weeks plus zeprumetostat at the RP2D in patients without prior PD-1 inhibitor therapy.

Drug: Tislelizumab; Drug: Zeprumetostat

Interventions

Tislelizumab DRUG

Tislelizumab 200 mg administered intravenously on day 1 of each 21-day cycle.

Phase II Cohort-N (PD-1 Inhibitor-Naive); Phase II Cohort-R (Prior PD-1 Exposed/Refractory); Phase Ib Dose Level A; Phase Ib Dose Level B

Zeprumetostat DRUG

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.

Phase II Cohort-N (PD-1 Inhibitor-Naive); Phase II Cohort-R (Prior PD-1 Exposed/Refractory); Phase Ib Dose Level A; Phase Ib Dose Level B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older.
• Pathologically confirmed NK/T-cell lymphoma.
• Relapsed or refractory disease after at least 1 prior asparaginase-based chemotherapy-containing regimen, with or without radiotherapy.
• At least 1 measurable or evaluable lesion according to Lugano 2014 criteria.
• ECOG performance status 0 to 2.
• Life expectancy greater than 12 weeks.
• Adequate hematologic, hepatic, renal, coagulation, and cardiac function.
• Recovery from prior anti-cancer treatment-related toxicities to CTCAE grade 1 or baseline, except for specified stable irreversible toxicities allowed by the investigator.
• Negative pregnancy test for women of childbearing potential.
• Willingness to use effective contraception.
• Written informed consent.

You may not qualify if:

• Prior treatment with any EZH1/2 or EZH2 inhibitor.
• Allogeneic hematopoietic stem cell transplantation within 5 years before study treatment.
• Autologous hematopoietic stem cell transplantation within 3 months before study treatment.
• Requirement for high-dose systemic corticosteroids or other immunosuppressive therapy within 14 days before study treatment, except permitted local/inhaled or short-course use.
• Cytotoxic chemotherapy not discontinued within 14 days before study treatment.
• Systemic anti-cancer therapy or investigational therapy within 4 weeks before study treatment.
• Major surgery within 4 weeks or radiotherapy within 90 days before study treatment.
• Active infection, including active/latent tuberculosis, HIV infection, active hepatitis B or C with detectable viral nucleic acid, or other clinically significant active viral infection.
• Uncontrolled cardiovascular disease.
• Persistent unresolved toxicities greater than CTCAE grade 1 from prior therapy, except alopecia.
• Gastrointestinal disorders or prior intestinal surgery that may impair oral drug absorption.
• Pregnancy or breastfeeding.
• Psychiatric illness or inability to provide informed consent.
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for the study.

Sponsors & Collaborators

• Rong Tao: lead
• Fudan University: collaborator

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200043, China

Location

Related Publications (4)

• Song Y, Liu Y, Li ZM, Li L, Su H, Jin Z, Zuo X, Wu J, Zhou H, Li K, He C, Zhou J, Qi J, Hao S, Cai Z, Li Y, Wang W, Zhang X, Zou J, Zhu J. SHR2554, an EZH2 inhibitor, in relapsed or refractory mature lymphoid neoplasms: a first-in-human, dose-escalation, dose-expansion, and clinical expansion phase 1 trial. Lancet Haematol. 2022 Jul;9(7):e493-e503. doi: 10.1016/S2352-3026(22)00134-X.

  PMID: 35772429 RESULT

• Song Y, Jin Z, Li ZM, Liu Y, Li L, He C, Su H, Zhou H, Li K, Hao S, Zuo X, Wu J, Li D, Wu M, Sun X, Qi J, Cai Z, Li Z, Li Y, Huang Y, Shen J, Xiao Z, Zhu J. Enhancer of Zeste Homolog 2 Inhibitor SHR2554 in Relapsed or Refractory Peripheral T-cell Lymphoma: Data from the First-in-Human Phase I Study. Clin Cancer Res. 2024 Apr 1;30(7):1248-1255. doi: 10.1158/1078-0432.CCR-23-2582.

  PMID: 38190117 RESULT

• Huang H, Tao R, Hao S, Yang Y, Cen H, Zhou H, Guo Y, Zou L, Cao J, Huang Y, Jin J, Zhang L, Yang H, Xing X, Zhang H, Liu Y, Ding K, Qi Q, Zhu X, Zhu D, Wang S, Fang T, Dai H, Shi Q, Yang J. Sugemalimab Monotherapy for Patients With Relapsed or Refractory Extranodal Natural Killer/T-Cell Lymphoma (GEMSTONE-201): Results From a Single-Arm, Multicenter, Phase II Study. J Clin Oncol. 2023 Jun 1;41(16):3032-3041. doi: 10.1200/JCO.22.02367. Epub 2023 Mar 30.

  PMID: 36996373 RESULT

• Tao R, Fan L, Song Y, Hu Y, Zhang W, Wang Y, Xu W, Li J. Sintilimab for relapsed/refractory extranodal NK/T cell lymphoma: a multicenter, single-arm, phase 2 trial (ORIENT-4). Signal Transduct Target Ther. 2021 Oct 27;6(1):365. doi: 10.1038/s41392-021-00768-0.

  PMID: 34702811 RESULT

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell; Recurrence

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rong Tao, MD & PhD

  Shanghai Cancer Center

  STUDY CHAIR

• Chuanxu Liu, MD & PhD

  Shanghai Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rong Tao, MD & PhD

CONTACT

008621-64175590; hkutao@hotmail.com

Chuanxu Liu, MD & PhD

CONTACT

008621-64175590; liuchaunxu@shca.or.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Model Details: In phase Ib, participants are assigned to 1 of 2 parallel dose levels of zeprumetostat in combination with fixed-dose tislelizumab. In phase II, participants are enrolled into 2 parallel cohorts based on prior exposure to PD-1 inhibitors.

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: March 31, 2026
• Study Start: March 23, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

CN (1)