Genotype-guided Targeted Agents Plus EZH2i for Primary Refractory PTCL

NCT07493330 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: Target
• Study Type: interventional
• Target: 86
• Locations: 0 countries
• Sites: N/A

Brief Summary

To evaluate the safety and efficacy of Zeprumetostat-based combination therapy, selected according to genotyping results, in patients with primary refractory peripheral T-cell lymphoma (PTCL).

Conditions

PTCL; Refractory

Keywords

PTCL; Genotype-guided; Zeprumetostat; Refractory

Outcome Measures

Primary Outcomes (2)

• Summary of DLT events (Phase Ib)

  Measure Description: Enroll 6 pts per cohort and observe the number of pts experiencing dose-limiting toxicity.

  At the end of Cycle 1 (each cycle is 28 days)

• Overall response rate (Phase Ⅱ)

  Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria

  At the end of Cycle 3 (each cycle is 28 days)

Secondary Outcomes (8)

• Complete response rate

  At the end of Cycle 3

• Disease Control Rate

  each cycle is 28 days

• Duration of response

  Baseline up to data cut-off

• Duration of complete response

  Baseline up to data cut-off

• Progression free survival

  Baseline up to data cut-off

Study Arms (4)

Zeprumetostat+Azacitadine (if with TET2 plus RHOA gene mutation)

EXPERIMENTAL

Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Azacitadine :100mg D1-D7, subcutaneous injection, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Azacitidine 100 mg D1-D5, subcutaneous injection for total 3 cycles.

Drug: Zeprumetostat+Azacitadine

Zeprumetostat+Decitabine (if with TP53 gene mutation)

EXPERIMENTAL

Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Decitabine 10mg/m2 D1-D5, intravenous infusion, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Decitabine 10mg/m2 D1-D3 for total 3 cycles.

Drug: Zeprumetostat+Chidamide

Zeprumetostat+Chidamide (if with CREBBP/EP300/KMT2C/KMT2D/NCOR2 gene mutation)

EXPERIMENTAL

Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Chidamide 30 mg biw orally, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Chidamide 20 mg biw for total 3 cycles.

Drug: Zeprumetostat+Decitabine

Zeprumetostat+Golidocitinib (if not above genotype)

EXPERIMENTAL

Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Golidocitinib 150 mg qd orally, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Golidocitinib 150 mg qod for total 3 cycles.

Drug: Zeprumetostat+Golidocitinib

Interventions

Zeprumetostat+Azacitadine DRUG

Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Azacitadine :100mg D1-D7, subcutaneous injection, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Azacitidine 100 mg D1-D5, subcutaneous injection for total 3 cycles.

Zeprumetostat+Azacitadine (if with TET2 plus RHOA gene mutation)

Zeprumetostat+Chidamide DRUG

Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Chidamide 30 mg biw orally, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Chidamide 20 mg biw for total 3 cycles.

Zeprumetostat+Decitabine (if with TP53 gene mutation)

Zeprumetostat+Golidocitinib DRUG

Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Golidocitinib 150 mg qd orally, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Golidocitinib 150 mg qod for total 3 cycles.

Zeprumetostat+Golidocitinib (if not above genotype)

Zeprumetostat+Decitabine DRUG

Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Decitabine 10mg/m2 D1-D5, intravenous infusion, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Decitabine 10mg/m2 D1-D3 for total 3 cycles.

Zeprumetostat+Chidamide (if with CREBBP/EP300/KMT2C/KMT2D/NCOR2 gene mutation)

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, male or female.
• Patients with a histopathologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) based on 2016 WHO classification
• Previously treated with 3 or 6 cycles of a CHOP-like regimen as first-line therapy and considered primary refractory. Patients with anaplastic large cell lymphoma (ALCL) must have adequately received brentuximab vedotin (BV) as part of their first-line treatment.
• Tumor tissue genotyping performed and results available prior to enrollment.
• ECOG 0, 1, or 2.
• Life expectancy greater than 3 months.
• Adequate organ function
• Contraception during study
• Informed consented

You may not qualify if:

• Has a prior malignancy other than the malignancies under study within 3 years without relieve
• Primary CNS lymphoma
• Known hypersensitivity to any study drug.
• Pregnant or lactation
• Active infection.
• Diseases and medical history:
• Requires continuous treatment with strong or moderate CYP3A inhibitors or CYP3A inducers
• Has multiple factors affecting oral medication administration (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
• Has a history of psychoactive substance abuse that cannot be discontinued
• Has any severe and/or uncontrolled disease.
• Uncontrollable autoimmune disease,
• Not able to comply to the protocol for mental or other unknown reasons
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.

Sponsors & Collaborators

• Ruijin Hospital: lead

Central Study Contacts

Weili Zhao

CONTACT

086-022-64370045; zwl_trial@163.com

Pengpeng Xu

CONTACT

pengpeng_xu@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice president of Ruijin Hospital

Study Record Dates

• First Submitted: March 19, 2026
• First Posted: March 25, 2026
• Study Start: March 23, 2026
• Primary Completion (Estimated): December 12, 2029
• Study Completion (Estimated): December 12, 2030
• Last Updated: March 25, 2026

Record last verified: 2026-03