Genotype-guided Targeted Agents Plus EZH2i for Primary Refractory PTCL

Genotype-guided Targeted Agents in Combination With EZH2 Inhibitor, Zeprumetostat for Primary Refractory Peripheral T-cell Lymphoma (PTCL), a Prospective, Open-label, Multi-center Study

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).

Peripheral T-cell lymphoma (PTCL) is a distinct and heterogeneous histopathologic subtype of non-Hodgkin lymphoma (NHL), accounting for ~10%. Patients with PTCL still have poor treatment response and prognosis under conventional CHOP regimen. Clinical outcomes of refractory patients are even poorer. Targeted drugs are warranted in this group of patients to improve survival. This prospective, multi-center, open-label study will evaluate the efficacy and safety of targeted drug in combination with Zeprumetostat, an EZH2 inhibitor in treatment of primary refractory peripheral peripheral T-cell lymphoma.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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:

  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.

• 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.