Study to Evaluate Efficacy and Safety of HH2853 in Relapsed/Refractory Peripheral T-cell Lymphoma

An Open-label, Multinational, Multicenter, Single-arm Phase Ⅰb/Ⅱ Study to Evaluate Efficacy and Safety of Oral HH2853, a Selective EZH1/2 Inhibitor, in Patients With Relapsed/Refractory Peripheral T-cell Lymphoma

This study is a an open-label, multinational, multicenter, single-arm Phase Ⅰb/Ⅱ Study to Evaluate Efficacy and Safety of Oral HH2853 in Patients with Relapsed/Refractory Peripheral T-cell Lymphoma.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Peripheral T-Cell Lymphoma (R/R PTCL)
• Intervention / Treatment: Drug: HH2853 Tablets

Detailed Description

This study includes Phase Ib and Phase II. In the Phase Ib, patients with R/R NHL (dose escalation) or R/R PTCL (dose expansion) who have received at least 1 line of prior systematic treatment and meet the inclusion/exclusion criteria in the protocol will be enrolled. Safety run-in study (Japan only): The objective of the safety run-in study in Japan is to evaluate the safety, tolerability, and PK profile of HH2853 in Japanese patients. The primary objective of the Phase Ib study is to determine the RP2D of HH2853 in PTCL patients. The secondary objectives are to evaluate the safety, preliminary efficacy and characterize the pharmacokinetic profile of HH2853 in R/R PTCL patients. A "3+3" design will be used in the dose escalation part with a starting dose of 400 mg BID. Based on the safety, efficacy and PK/PD data and HH2853-G101 data, 1-2 dose levels could be expanded, 10-15 R/R PTCL patients for each dose level. Approximately 21-48 patients will be enrolled in total.

In the Phase II (multi-national): patients with R/R PTCL who have received at least one prior systemic combination chemotherapy and at least one new drug therapy and meet the inclusion/exclusion criteria in the protocol will be enrolled. The Phase II study will be started once the RP2D is determined. The Phase II study is a single-arm study and will be enrolled in approximately 66 efficacy-evaluable R/R PTCL patients who had received at least one prior systemic combination chemotherapy and at least one new drug therapy. The primary objective of the Phase II study is to evaluate the efficacy of HH2853 of R/R PTCL patients who have received at least one prior systemic combination chemotherapy and at least one new drug therapy (ORR, BIRC evaluation); The secondary objectives will be continued to further evaluate the efficacy, safety, tolerability and PK characteristics of HH2853 of R/R PTCL patients who have received at least 1 line of prior systemic therapy.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Haiying Jia; Phone Number: 86-20568888; Email: haiying.jia@haihepharma.com

Study Locations

• China
  • Chengdu
    • Chengdu, Chengdu, China
      • Recruiting
      • Sichuan Cancer Hospital
      • Contact: Huangming Hong, MD; Phone Number: 86-13570431657; Email: honghm3@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• main inclusion:

  1. Tumor types and prior antitumor therapy: Phase Ib:Dose Escalation: All enrolled patients must have histologically confirmed diagnosis NHL who have received at least one line of prior systematic treatment (and ≤ 5 lines) and relapses or refractory. Phase Ib dose expansion part: All enrolled patients must have histologically confirmed diagnosis of PTCL, including subtypes: PTCL-NOS, AITL, ALK + ALCL, ALK-ALCL, NKTCL, enteropathy associated T-cell lymphoma (EATL), monomorphic epitheliotropic internal T-cell lymphoma (MEITL), Hepatosplenic T-cell lymphoma (HSTCL), follicular T-cell lymphoma (FTCL), Nodal peripheral T-cell lymphoma with TFH phenotype (Nodal PTCL-TFH) and other invasive T-cell sources NHL at the investigator and sponsor's discretion (except highly invasive). All enrolled patients had relapsed or refractory diseases after receiving 1-line systematic treatment (≤ 3 lines). Phase II: All enrolled patients must have histologically confirmed diagnosis of PTCL, including subtypes: PTCL-NOS, AITL, ALK+ALCL, ALK-ALCL, NKTCL, EATL, MEITL, HSTCL, FTCL, Nodal PTCL-TFH et al. Patients must have histologically confirmed diagnosis of R/R PTCL who have received at least one line of prior systematic combination chemotherapy and at least one new drug therapy (prior antitumor treatment lines ≤4 lines) : relapse and/or refractory.
  2. Availability of qualified tissue samples by patient for pathological diagnosis by the central laboratory.
  3. The Eastern cooperative oncology group (ECOG) score 0-1.
  4. Life expectancy ≥ 3 months before starting HH2853 treatment.
  5. Sufficient bone marrow, liver and renal functions.

Exclusion Criteria:

• main criteria:

  1. Previous treatment with EZH2 or EZH1/2 inhibitors.
  2. Central nervous system invasion.
  3. Any previous history of bone marrow malignancy, including myelodysplastic syndrome (MDS).
  4. Received medications that are known potent CYP3A4 inducers/inhibitors within 1 week prior to first dose.

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: Dose escalation and expansion study of HH2853; To determine the RP2D of HH2853 in PTCL patients.	Drug: HH2853 Tablets; 25mg, 100mg and 200 mg BID oral administration; Other Names: HH2853

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib: To determine the RP2D of HH2853 in PTCL patients	Determine RP2D of HH2853	28-day treatment cycles
Phase II: To evaluate the efficacy of HH2853 of R/R PTCL patients who have received at least one prior systemic combination chemotherapy and at least one new drug	ORR will be based on the blinded independent review committee (BIRC). Assessment of oncologic response will be performed according to the 2014 edition of the Lugano Criteria for Efficacy [Lugano]	28-day treatment cycles

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib: 1. Preliminary efficacy of HH2853 in R/R PTCL patients;	Investigator assessed: complete response rate (CRR)	28-day treatment cycles
Phase Ib: 1. Preliminary efficacy of HH2853 in R/R PTCL patients;	Duration of response (DoR)	28-day treatment cycles
Phase Ib: 1. Preliminary efficacy of HH2853 in R/R PTCL patients;	Disease control rate (DCR)	28-day treatment cycles
Phase Ib: 1. Preliminary efficacy of HH2853 in R/R PTCL patients;	Time to response (TTR)	28-day treatment cycles
Phase Ib: 2.To characterize the pharmacokinetic profile of HH2853	Area under the concentration-time curve (AUC)	28-day treatment cycles
Phase Ib: 2.To characterize the pharmacokinetic profile of HH2853	Maximum plasma concentration (Cmax)	28-day treatment cycles
Phase Ib: 2.To characterize the pharmacokinetic profile of HH2853	Trough concentration (Cmin)	28-day treatment cycles
Phase Ib: 2.To characterize the pharmacokinetic profile of HH2853	Time to maximum plasma concentration (Tmax)	28-day treatment cycles
Phase Ib: 2.To characterize the pharmacokinetic profile of HH2853	Apparent clearance (CL/F)	28-day treatment cycles
Phase Ib: 2.To characterize the pharmacokinetic profile of HH2853	Terminal half-life (t1/2)	28-day treatment cycles
Phase II: 1.To further assess the other efficacy of HH2853 of R/R PTCL patients who have received at least one prior systemic combination chemotherapy and at least one new drug (such as Chidamide, Pralatrexate and Brentuximab vedotin, et al.) therapy	ORR assessed by investigator	28-day treatment cycles
Phase II: 1.To further assess the other efficacy of HH2853 of R/R PTCL patients who have received at least one prior systemic combination chemotherapy and at least one new drug (such as Chidamide, Pralatrexate and Brentuximab vedotin, et al.) therapy	Complete response rate (CRR)	28-day treatment cycles
Phase II: 1.To further assess the other efficacy of HH2853 of R/R PTCL patients who have received at least one prior systemic combination chemotherapy and at least one new drug (such as Chidamide, Pralatrexate and Brentuximab vedotin, et al.) therapy	Progression-free survival (PFS)	28-day treatment cycles
Phase II: 1.To further assess the other efficacy of HH2853 of R/R PTCL patients who have received at least one prior systemic combination chemotherapy and at least one new drug (such as Chidamide, Pralatrexate and Brentuximab vedotin, et al.) therapy	Duration of response (DoR)	28-day treatment cycles
Phase II: 1.To further assess the other efficacy of HH2853 of R/R PTCL patients who have received at least one prior systemic combination chemotherapy and at least one new drug (such as Chidamide, Pralatrexate and Brentuximab vedotin, et al.) therapy	Disease control rate (DCR)	28-day treatment cycles
Phase II: 1.To further assess the other efficacy of HH2853 of R/R PTCL patients who have received at least one prior systemic combination chemotherapy and at least one new drug (such as Chidamide, Pralatrexate and Brentuximab vedotin, et al.) therapy	Time to response (TTR)	28-day treatment cycles
Phase II: 1.To further assess the other efficacy of HH2853 of R/R PTCL patients who have received at least one prior systemic combination chemotherapy and at least one new drug (such as Chidamide, Pralatrexate and Brentuximab vedotin, et al.) therapy	Overall survival (OS) by BIRC	28-day treatment cycles
Phase II: 1.To further assess the other efficacy of HH2853 of R/R PTCL patients who have received at least one prior systemic combination chemotherapy and at least one new drug (such as Chidamide, Pralatrexate and Brentuximab vedotin, et al.) therapy	Overall survival (OS) by investigator	28-day treatment cycles
Phase II: 2. To evaluate the safety and tolerability of HH2853	Duration and severity of adverse events (AEs)	28-day treatment cycles
Phase II: 3. To characterize the population pharmacokinetic profile of HH2853	Area under the concentration-time curve (AUC)	28-day treatment cycles
Phase II: 3. To characterize the population pharmacokinetic profile of HH2853	Maximum plasma concentration (Cmax)	28-day treatment cycles
Phase II: 3. To characterize the population pharmacokinetic profile of HH2853	Steady-state trough concentration (Cmin)	28-day treatment cycles
Phase II: 3. To characterize the population pharmacokinetic profile of HH2853	Time to maximum plasma concentration (Tmax)	28-day treatment cycles
Phase II: 3. To characterize the population pharmacokinetic profile of HH2853	Apparent clearance (CL/F)	28-day treatment cycles
Phase II: 3. To characterize the population pharmacokinetic profile of HH2853	Half life (t1/2)	28-day treatment cycles

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib and II: 1. To explore biomarkers related to response and effect of HH2853	mutation status of EZH2	28-day treatment cycles
Phase Ib and II: 2. To explore the correlation between HH2853 exposure with safety, efficacy and pharmacokinetic parameters	Correlation between exposure (Cmax or AUC) and safety/efficacy/pharmacodynamic biomarkers (trimethylation of histone H3 at lysine 27 [H3K27me3])	28-day treatment cycles

Collaborators and Investigators

• Sponsor: Haihe Biopharma Co., Ltd.
• Investigators: Principal Investigator: Tongyu Li, MD, Sichuan Cancer Hospital and Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2022
• Primary Completion (Actual): October 31, 2025
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: March 20, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): April 4, 2025

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Relapsed/Refractory; Peripheral T-cell Lymphoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, T-Cell, Peripheral
• Other Study ID Numbers: HH2853-G202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD based on business strategy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No