Multi-Cohort Study of Zeprumetostat Combinations for Relapsed/Refractory PTCL

A Multi Cohort Exploratory Clinical Study of the EZH2 Inhibitor Zeprumetostat Combination Regimen in Relapsed/Refractory Peripheral T Cell Lymphoma

This is a single-arm, multi-cohort, multicenter, phase Ib/IIa clinical study designed to evaluate the safety and efficacy of Zeprumetostat (an EZH2 inhibitor) in combination with different therapeutic agents/regimens - specifically, the JAK1 inhibitor golidocitinib and the GemOx chemotherapy regimen (gemcitabine plus oxaliplatin) - in patients with relapsed or refractory peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and T-follicular helper cell lymphoma (TFHL). The trial comprises a phase Ib dose-escalation phase and a phase IIa dose-expansion phase. Two combination cohorts are established: Cohort A (zemitostatin + golidocitinib) and Cohort B (zemitostatin + GemOx). Subjects will be randomly assigned to either Cohort A or Cohort B.

Study Overview

• Status: Not yet recruiting
• Conditions: PTCL-NOS
• Intervention / Treatment: Drug: Zeprumetostat( an EZH2 inhibitor) + X

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhang huilai, MD; Phone Number: +86-18622221228; Email: huilaizhangtz@163.com

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or older, both males and females are eligible;

2. Histologically confirmed peripheral T-cell lymphoma (PTCL) including PTCL-NOS and TFHL that has relapsed or is refractory after at least one line of systemic therapy. The definitions are as follows:

   Relapse: Patients who achieved a Complete Response (CR) in previous treatments and have new lesions at the original site or elsewhere; Refractory: Patients who did not achieve CR after adequate treatment. For nasal-type NK/T-cell lymphoma, previous treatments must have included a chemotherapy regimen containing asparaginase;

3. Patients who have undergone prior hematopoietic stem cell transplantation are allowed;
4. ECOG PS 0-2
5. Life expectancy greater than 3 months.
6. Adequate organ function
7. Contraception during study
8. Informed consented

Exclusion Criteria:

1. Prior treatment with EZH2 inhibitors or EZH1/2 inhibitors before enrollment;
2. Peripheral T-cell lymphoma of subtypes other than PTCL-NOS and TFHL;
3. History of other primary invasive malignancies that have not been in remission or have been in remission for no more than 3 years;
4. Central nervous system involvement (meningeal or parenchymal);
5. Known hypersensitivity to any study drugs;
6. Participation in another clinical trial of an investigational drug within 4 weeks prior to the start of the study.
7. Pregnant or lactation
8. Active infection.

9. Diseases and medical history:

   1. Requires continuous treatment with strong or moderate CYP3A inhibitors or CYP3A inducers
   2. Has multiple factors affecting oral medication administration (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
   3. Has a history of psychoactive substance abuse that cannot be discontinued
   4. Has any severe and/or uncontrolled disease.
10. Uncontrollable autoimmune disease,
11. Not able to comply to the protocol for mental or other unknown reasons
12. Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zeprumetostat + X; Zeprumetostat+JAK1 inhibitor/GemoX	Drug: Zeprumetostat( an EZH2 inhibitor) + X; Zeprumetostat( an EZH2 inhibitor) + JAK1 inhibitor or GemOx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of DLT events (Phase Ib)	A Phase Ib Dose-Finding Study of Zeprumetostat in Combination Using a 3+3 Design	At the end of Cycle 1 (each cycle is 21 days)
Overall response rate (Phase Ⅱ)	Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment EZH2+JAK1/GeMox	Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate	Complete Response Rate (CRR) is defined as the proportion of subjects who achieve CR after treatment EZH2+JAK1/GeMox	Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1)
Duration of response	Duration of Remission (DoR) is defined as the time from the first documentation of remission (CR or PR) to the first documented relapse evidence of the responders.	Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1)
Progression free survival	Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first	Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1)
Overall survival	Overall survival was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event. of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first	Through study completion, an average of 3 years after EZH2+JAK1/GemOx (Day 1)
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events	Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1)

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): July 30, 2030
• Study Completion (Estimated): July 30, 2031

Study Registration Dates

• First Submitted: July 7, 2026
• First Submitted That Met QC Criteria: July 21, 2026
• First Posted (Actual): July 24, 2026

Study Record Updates

• Last Update Posted (Actual): July 24, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: MA-PTCL-II-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No