SHR2554 Plus Liposomal Mitoxantrone as First-line Treatment for Peripheral T-cell Lymphoma (PTCL)

An Open-label, Multicenter, Phase Ib/II Exploratory Clinical Study of EZH2 Inhibitor SHR2554 in Combination With Liposomal Mitoxantrone for the First-line Treatment of Peripheral T-cell Lymphoma

This is a single-arm, multicenter, Phase Ib/IIa study designed to explore the efficacy and safety of SHR2554 in combination with liposomal mitoxantrone for the treatment of patients with treatment-naive peripheral T-cell lymphoma (PTCL). The study is divided into a Phase Ib safety lead-in phase and a Phase IIa dose expansion phase.

Study Overview

• Status: Not yet recruiting
• Conditions: First Line Treatment; PTCL
• Intervention / Treatment: Drug: SHR2554 combined with Liposomal Mitoxantrone

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Liang Huang; Phone Number: +86 022-23608126; Email: huangliang@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years old,regardless of gender;
2. Centrally confirmed histopathological/cytologic diagnosis of PTCL with the following subtypes:Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS);Follicular helper T (TFH) cell lymphoma of lymph nodes, including angioimmunoblastic, follicular, NOS; Enteropathy-associated T-cell lymphoma(EATL); Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)and any other PTCL subtypes deemed by the investigator to be eligible for inclusion.
3. No prior anti-tumor therapy.
4. There must be at least one measurable or evaluable lesion that meets the Lugano 2014 criteria for lymphoma: Measurable lesion: Nodal lesions with major diameter greater than 1.5cm and minor diameter greater than 1.0cm as assessed by PET/CT or Computed Tomography (CT) and/or Magnetic Resonance Imaging (MRI); Or the length of extranodal lesions >1.0cm; 2)Evaluable lesions: PET-CT showed increased uptake in lymph nodes or extranodal regions (higher than liver) and imaging features consistent with lymphoma;
5. ECOG performance status score: 0-2;
6. Expected survival time ≥3 months;
7. Have adequate organ and bone marrow functiont;
8. No concurrent hemophagocytic lymphohistiocytosis (HLH). If a patient has clinically diagnosed HLH, enrollment eligibility will be determined by the investigator based on an evaluation of the patient's general physical condition following targeted anti-HLH therapy.
9. Women of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose of medication; Effective contraception should be used from the time of informed consent until 6 months after the last dose of study drug.
10. Capable of understanding the study procedures and voluntarily signing a written informed consent form (ICF).;

Exclusion Criteria:

1. Prior treatment with epigenetic agents before enrollment;
2. Patients with a history of severe cardiac disease, history of radiation therapy to the mediastinal/pericardial region, cumulative anthracycline dose > 550 mg (doxorubicin equivalent), prior use of mitoxantrone, baseline left ventricular ejection fraction (LVEF) < 50%, or history of exposure to other cardiotoxic drugs;
3. History of other primary aggressive malignancies that are not in remission, or have been in remission for less than 3 years;
4. Primary central nervous system (CNS) lymphoma or secondary CNS involvement.
5. Known allergy or hypersensitivity to the study drugs or their related metabolites;
6. Currently participating in another clinical study, or less than 4 weeks elapsed from the end of treatment in a previous clinical study to the planned start of study treatment;
7. Pregnant or lactating women;
8. Active infections;
9. Medical History and Concurrent Conditions;
10. History of Human Immunodeficiency Virus (HIV) infection and/or Acquired Immunodeficiency Syndrome (AIDS);
11. Patients with mental disorders or those unable to provide informed consent
12. Any other condition deemed by the investigator to be unsuitable for study enrollment;

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: SHR2554 combined with Liposomal Mitoxantrone

Drug: SHR2554 combined with Liposomal Mitoxantrone; Patients will receive 6 cycles of SHR2554 combined with liposomal mitoxantrone as induction therapy. All patients who achieve a complete response (CR) after induction therapy are eligible for transplantation. Patients achieving CR or partial response (PR), as well as those post-transplantation, may receive SHR2554 maintenance therapy in 28-day cycles. Maintenance therapy will continue until disease progression or other reasons for discontinuation. The maximum duration of SHR2554 administration in the maintenance phase will not exceed 24 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-Limiting Toxicities (DLT)	Adverse events (AE) defined as DLT events per protocol	Cycle 1 (28 days)
Complete response (CR) rate	The proportion of subjects evaluated as complete response (CR) according to Lugano 2014 efficacy evaluation criteria	up to 6 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events(AE)	The safety of the drug was evaluated by NCI-CTC AE 6.0 standard. Hematologic and non-hematologic toxicity.	From the first day of medication to 28 days after the last dose
Objective response rate (ORR)	The proportion of subjects evaluated as complete response (CR) and partial response (PR) according to Lugano 2014 efficacy evaluation criteria	up to 6 months after enrollment
Duration of Response (DOR)	The time from the first assessment of CR/PR to the first assessment of PD or death from any cause in the subject	up to 2.5 years post first treatment
Duration of complete response (CR)	The time from the first assessment of CR to the first assessment of PD or death from any cause in the subject	up to 2.5 years post first treatment
Progression-free Survival (PFS)	From the time subjects were enrolled to the time of disease progression (in any way) or death from any cause.	Up to 2.5 years
Overall survival (OS)	From the date of inclusion to date of death, irrespective of cause.	Up to 2.5 years

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: July 21, 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

• Keywords: EZH2 inhibitor; SHR2554; Liposomal Mitoxantrone; Zeprumetostat; First-line Treatment of PTCL
• Other Study ID Numbers: IIT2026083

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