Tislelizumab Plus Zeprumetostat for Relapsed or Refractory NK/T-Cell Lymphoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorRong Tao
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Tislelizumab
DrugTislelizumab 200 mg administered intravenously on day 1 of each 21-day cycle.
Zeprumetostat
DrugZeprumetostat (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.
Treatment groups
107 Participants
are divided into 4 treatment groupsGroup A: Phase Ib Dose Level AExperimental treatment 2 interventions
Group B: Phase Ib Dose Level BExperimental treatment 2 interventions
Group C: Phase II Cohort-R (Prior PD-1 Exposed/Refractory)Experimental treatment 2 interventions
Group D: Phase II Cohort-N (PD-1 Inhibitor-Naive)Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
During phase Ib, up to 12 weeks2
Objective Response Rate (ORR) at Week 12
Objective response rate assessed by independent blinded imaging review according to Lugano 2014 criteria during phase II.
Time frame
Week 12Secondary outcomes
1
Complete Response Rate (CRR)
Proportion of participants whose best overall response is complete response (CR) at week 12, as assessed according to Lugano 2014 criteria.
Time frame
12 weeks2
Duration of Response (DOR)
Duration of response is defined as the time from first documented complete response (CR) or partial response (PR) to disease progression, relapse, or death, according to Lugano 2014 criteria.
Time frame
From first documented CR or PR until first documented disease progression, relapse, or death, up to 36 months3
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from study enrollment/first dose to the first documentation of progressive disease or death from any cause, whichever occurs first.
Time frame
From first dose until first documented disease progression or death from any cause, up to 36 months4
Overall Survival (OS)
Overall survival is defined as the time from study enrollment/first dose to death from any cause.
Time frame
From first dose until death from any cause, up to 36 monthsOther outcomes
1
Objective Response Rate (ORR) in Predefined Biomarker Subgroups
Objective response rate at week 12, assessed according to Lugano 2014 criteria, in predefined biomarker subgroups including PD-L1, EZH2/H3K27me3, EBV-DNA, ctDNA clearance, and other prospectively defined biomarker categories.
Time frame
12 weeksSponsors and contacts
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Source ClinicalTrials.gov