An Open-label, Multicenter, Exploratory Clinical Study of the EZH2 Inhibitor Zeprumetostat in Combination Therapy for Patients With Relapsed or Refractory Mature T-cell and NK-cell Lymphomas.
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 60
- Primary Endpoint
- DLT for Phase 1b
Overview
Brief Summary
This is a prospective, multicenter, open-label, phase Ib/II clinical study to evaluate the safety and efficacy of EZH2 inhibitor Zeprumetostat in combination therapy for patients with relapsed or refractory mature T-cell and NK-cell lymphomas.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily participate in the clinical study; fully understand and be informed about the study and sign the Informed Consent Form (ICF); willing to comply with and capable of completing all trial procedures;
- •Age ≥ 18 years
- •Pathologically confirmed mature T-cell and NK-cell lymphomas.
- •Using the Lugano 2014 criteria, the patient must have at least one measurable or evaluable lesion
- •Participants must have experienced disease progression, treatment failure, or intolerance following standard therapy. Patients with ALCL are required to have previously received anti-CD30-targeted therapy, while patients with NKTCL must have previously been treated with pegaspargase or L-asparaginase.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Adequate organ and bone marrow function
Exclusion Criteria
- •Lymphoma involvement in the central nervous system or meninges
- •Active infections
- •Prior treatment with an EZH2 inhibitor or an EZH1/2 dual inhibitor that was discontinued due to intolerance to toxicity;
- •For patients enrolled in Cohort 1, prior treatment with a JAK inhibitor that was discontinued due to intolerance to toxicity;
- •For patients enrolled in Cohort 2, prior treatment with an HDAC inhibitor that was discontinued due to intolerance to toxicity.
- •History of Human Immunodeficiency Virus (HIV) infection and/or Acquired Immunodeficiency Syndrome (AIDS).
- •Patients with mental disorders or those unable to provide informed consent
- •Any other condition deemed by the investigator to be unsuitable for study enrollment;
- •Pregnant or breastfeeding women, and subjects of childbearing potential who are unwilling to use contraception;
- •Individuals with a known hypersensitivity to any of the investigational drugs.
Arms & Interventions
Zeprumetostat Combined with Golidocitinib or Chidamide
In Cohort 1, patients will receive Zeprumetostat in combination with Golidocitinib, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Golidocitinib at the RP2D dose level for an extension study. In Cohort 2, patients will receive Zeprumetostat in combination with Chidamide, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Chidamide at the RP2D dose level for an extension study.
Intervention: Zeprumetostat (Drug)
Zeprumetostat Combined with Golidocitinib or Chidamide
In Cohort 1, patients will receive Zeprumetostat in combination with Golidocitinib, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Golidocitinib at the RP2D dose level for an extension study. In Cohort 2, patients will receive Zeprumetostat in combination with Chidamide, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Chidamide at the RP2D dose level for an extension study.
Intervention: Golidocitinib (Drug)
Zeprumetostat Combined with Golidocitinib or Chidamide
In Cohort 1, patients will receive Zeprumetostat in combination with Golidocitinib, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Golidocitinib at the RP2D dose level for an extension study. In Cohort 2, patients will receive Zeprumetostat in combination with Chidamide, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Chidamide at the RP2D dose level for an extension study.
Intervention: Chidamide (Drug)
Outcomes
Primary Outcomes
DLT for Phase 1b
Time Frame: The first cycle after administration (each cycle is 28 days)
To identify the dose-limiting toxicity
Overall response rate(ORR) for Phase 2
Time Frame: Up to 24 months
The proportion of patients who achieve complete remission (CR) or partial remission (PR) as the best response.
RP2D for phase Ib
Time Frame: The first cycle after administration (each cycle is 28 days)
To identify the recommended phase 2 dose
Secondary Outcomes
- Complete response rate (CRR)(Up to 24 months)
- Duration of Response(DOR)(Up to 4 years)
- Progression-free survival(PFS)(Up to 4 years)
- Overall survival(OS)(Up to 4 years)
Investigators
Qingqing Cai
Principal Investigator
Sun Yat-sen University