Evaluate the Safety and Clinical Activity of HH2853

A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of HH2853 in Patients With Relapsed/Refractory Non-Hodgkin's Lymphomas or Advanced Solid Tumors

This is an open-label, multicenter, first-in-human phase I/II study which is composed of 3 parts: phase I dose escalation, phase I dose extension and phase II. HH2853 will be administered orally on a continuous BID schedule on a continuous 28-day treatment cycle.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor; Epithelioid Sarcoma; Peripheral T Cell Lymphoma; FL Lymphoma
• Intervention / Treatment: Drug: HH2853 Tablets

Detailed Description

Phase I:

Phase I dose escalation The accelerated titration (ATD) incorporated with Bayesian Optimal Interval design (BOIN) will be used to assess the DLT, safety, tolerability, MTD and furthermore, to establish the RP2D. DLT assessment is only applicable to phase I dose escalation.

Eligible patients will be enrolled in the ascending dose until MTD/RP2D is established.

Phase I dose extension During the dose escalation phase, a dose extension with additional patients will be included in order to further evaluate the tolerability, pharmacokinetics, and efficacy at doses that have been evaluated as safe. The number of patients to be enrolled in each dose extension cohort is up to 15, but the final number of dose level can be determined and the final patient number at each dose level can be adjusted slightly based on available safety, efficacy, PK, and PD data upon agreement from sponsor and investigators (e.g. safety evaluation meeting). For phase I dose extension, approximately 30 patients will be enrolled based on initial estimate, but the final total number of patients will depend on the number of dose levels extended and patient number at each dose level.

The total number of patients is estimated to be approximately 60 patients for phase I dose escalation and dose extension, but the final total number of patients will depend upon the number of dose cohorts to reach MTD/RP2D, and patient number at each dose level.

Phase II（China Only）:

Phase II is planned after the completion of phase I. Up to approximately 193 patients will be enrolled as outlined below:

• Cohort 1: Relapsed/Refractory FL (n≈56)
• Cohort 2: Epithelioid sarcoma (n≈77)
• Cohort 3: Relapsed/Refractory PTCL, other relapsed/refractory Non-Hodgkin's lymphomas with EZH2 mutation, or advanced solid tumors with specific genetic alterations, including EZH2 mutation, INI1 deficiency, BAP1 deficiency, ARID1A mutation, or/and SMARCA4 mutation (n≈60)

• Study Type: Interventional
• Enrollment (Estimated): 254
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Haiyue Chen; Phone Number: +86 21 20568888; Email: haiyue.chen@haihepharma.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Cancer Hospital
    • Contact: Zhengfu Fan; Email: zhengfufan@126.com
  • Guangzhou, China
    • Recruiting
    • Sun Yat-sen University Cancer Hospital
    • Contact: Jin Wang; Email: wangjinr@sysucc.org.cn
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • The First Affiliated Hospital of Anhui Medical University
      • Contact: Kangsheng Gu; Email: 13805692145@163.com
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Lin Shen; Email: linshenpku@163.com
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Jun Zhu; Email: zhujun3346@163.com
      • Contact: Yuqin Song; Email: songyuqin622@163.com
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Jishuitan Hospital
      • Contact: Xiaohui Niu; Email: niuxiaohui@263.net
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen University Cancer Hospital
      • Contact: Zhiming Li; Email: lizhm@sysucc.org.cn
      • Principal Investigator: Jundong Li
  • Guangxi
    • Nanning, Guangxi, China
      • Recruiting
      • Affiliated Tumor Hospital of Guangxi Medical University
      • Contact: Hong Cen; Email: cen_hong@163.com
      • Principal Investigator: Weimin Xie
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Weitao Yao; Email: ywtwhm@163.com
      • Contact: Keshu Zhou; Email: drzhouks77@163.com
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Principal Investigator: Jing Chen
      • Contact: Liling Zhang; Email: zlladct@163.com
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Cancer hospital
      • Principal Investigator: Xianan Li
      • Contact: Hui Zhou; Email: Zhouhui9403@126.com
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Affiliated Drum Tower Hospital, Medical School of Nanjing University
      • Contact: Tianru Li; Email: li_rutian@163.com
  • Liaoning
    • Shenyang, Liaoning, China
      • Recruiting
      • Shengjing Hospital Of China Medical University
      • Contact: Wei Yang; Email: sjyangw@163.com
    • Shenyang, Liaoning, China
      • Recruiting
      • Liaoning Cancer Hospital&Institute
      • Contact: Xiaojing Zhang; Email: Zhangxiaojingwu@163.com
  • Shandong
    • Linyi, Shandong, China
      • Recruiting
      • Linyi Tumor Hospital
      • Contact: Zhen Wang; Email: LYSZLYYNSK@163.com
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Zhongshan Hospital Fudan University
      • Contact: Yuhong Zhou; Email: zhou.yuhong@zs-hospital.sh.cn
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Shanghai Sixth People's Hospital
      • Contact: Yang Dong; Email: dongyang6405@163.com
  • Shanxi
    • Taiyuan, Shanxi, China
      • Recruiting
      • Shanxi Cancer Hospital
      • Contact: Yuxia Shi; Email: 1274174089@qq.com
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: Yu Jiang
      • Contact: Lijun Zou; Email: hxlcyxy@163.com
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Recruiting
      • Tianjin cancer hospital
      • Principal Investigator: Jilong Yang
      • Contact: Shiyong Zhou; Email: zsy1003@163.com
      • Principal Investigator: Yun Yang
      • Principal Investigator: Shiyong Zhou
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Cancer Hospital
      • Principal Investigator: Haiyan Yang
      • Contact: Meiyu Fang; Email: fangmy@zjcc.org.cn
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Completed
      • Mayo Clinic
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Completed
      • Mayo Clinic
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Completed
      • Mayo Clinic
  • Texas
    • San Antonio, Texas, United States, 78240
      • Completed
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Provided signed written informed consent prior to initiation of any study-related procedures;
2. Males and females ≥ 18years of age at the time of consent are obtained (or meet the country's regulatory defined adult legal age);
3. Tumor type criteria:

The specific requirements for specific subtypes of recurrent/refractory non Hodgkin's lymphoma (NHL) confirmed by histology are as follows:

Histologically confirmed follicular lymphoma (FL) that has been treated with at least two lines of systemic therapy (at least one regimen based on anti-CD20 monoclonal antibodies) according to GELF criteria or as determined by researchers (Grade 1-3a); Relapsed/refractory diffuse large B-cell lymphoma - non-specific (DLBCL NOS, 2016 World Health Organization Lymphoma Classification) that has received at least two treatment regimens in the past (at least one with CD20 monoclonal antibody as the main treatment, with a maximum number of treatment lines<5), and is not a candidate for salvage treatment or autologous/allogeneic stem cell transplantation.

Relapsed/refractory clinicopathologically documented PTCL with at least 1 line of prior systemic treatment (maximum <5 lines). Solid tumors that meet the following criteria:

1. Histologically or cytologically documented advanced recurrent or metastatic solid tumor.
2. Phase I dose escalation: Measurable or evaluable lesions by RECIST v1.1 in at least 1 site; phase I dose extension and phase II: Measurable target lesions by RECIST v1.1 in at least 1 site. (Lesions that have been treated with radiotherapy or other local treatment are generally considered unmeasurable unless there is definite progression of the lesion.)
3. Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent. One of the following criteria should be met.

Patients must experience at least one prior standard therapy. Disease progression occurred on or after last line of therapy, or intolerant to last line of therapy (maximum ≤3 lines, Patients without treatment options available known to provide clinical benefit are also eligible upon agreement from investigator and sponsor) There is no approved therapy, or for which standard therapy is unsuitable or refused by patients after being fully informed.

For epithelioid sarcoma in Phase I and Phase II cohort 2:

1. Confirmed by local histology or cytology
2. Patients with unresectable locally delayed or metastatic epithelioid sarcoma who have undergone treatment (including those who have failed treatment and developed intolerable toxicity).

For solid tumors in Phase I and Phase II queue 3:

1. Confirmed by local pathology as advanced recurrent or metastatic solid tumor.
2. Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent 4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1; 5. Availability of archival tissue within three years 6. Relapsed/Refractory FL, Epithelioid sarcoma, relapsed/refractory PTCL, other relapsed/refractory non-Hodgkin's lymphomas with EZH2 mutation, and advanced solid tumors with specific genetic alterations, including EZH2 mutation, INI1 deficiency, BAP1 deficiency, ARID1A mutation, or/and SMARCA4 mutation 7. Predicted life expectancy of ≥ 3 months; 8. Patient must meet the following laboratory values: 1.Serum total Bilirubin ≤ 1.5 x ULN or ≤ 3.0 mg/dL for patients with Gilbert's syndrome 2.AST/SGOT and ALT/SGPT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present 3.24-hour creatinine clearance (calculated* or measured value**)≥ 50 mL/min 4.Platelets ≥ 1 x LLN (no Platelet transfusion for 7 days prior to screening) 5.Hemoglobin (Hgb) ≥ 9 g/dL 6.Absolute Neutrophil Count (ANC) ≥ 1.0 x 10^9/L 7.Adequate coagulation function: International normalized ratio (INR) <1.3 (or <3.0 on anticoagulants) 9. Measurable lesion

Exclusion Criteria:

1. Any cancer-directed therapy within 28 days or five half-lives prior to first dose; Small molecule anticancer therapy within 2 weeks or five half-lives; Local radiotherapy within 14 days of first dose.
2. Symptomatic CNS metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease.
3. Patients with prior transplant are excluded;
4. Major surgery within 4 weeks prior to first dose;
5. A prohibited medication or expected to require any of these medications during treatment with study drug within 2 weeks of first dose;
6. HIV (human immunodeficiency virus) infection, active hepatitis B or hepatitis C patients (HBsAg positive patients with HBV (hepatitis B virus) DNA ≥ 10^3 copies or ≥ 200 IU/mL; HCV antibody test results are positive, and HCV (hepatitis C virus) RNA PCR test results are positive).
7. Concomitant malignancies or previous malignancies
8. Concurrent use of therapeutic warfarin is allowed. However, anticoagulants that do not have reversal agents available are prohibited except low molecular weight heparin and direct oral anticoagulants.
9. Any toxicities from prior treatment that have not recovered to ≤ CTCAE Grade 1
10. There were ≥ 3 lesions with punctate bleeding, any active bleeding, intratumoral bleeding, known bleeding tendencies, or treatment with antiplatelet/antithrombotic drugs.
11. Gastrointestinal condition which could impair absorption of study medication;
12. Psychological, familial, sociological or geographical conditions that do not permit compliance with the protocol;
13. Cardiac exclusion criteria:

1.History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 3 months prior to first dose of study drug; 2.Fridericia's corrected QT interval (QTcF) > 450 ms (for male) and > 470 ms (for female) on ECG conducted during screening; 3.Congenital long QT syndrome, or any known history of torsade de pointes (TdP), or family history of unexplained sudden death; 4.History or current evidence of serious uncontrolled ventricular arrhythmias; 5.Symptomatic congestive heart failure (Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system) within the previous 3 months; 6.Left ventricular ejection fraction (LVEF) < 50%; 14. Any evidence of serious active infections requiring antibiotics; 15. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug or their excipients; 16. Pregnant or breast-feeding female; 17. Contraception: 18. Other serious illness or medical conditions at the Investigator's discretion, that may influence study results 19. Previously received treatment with EZH2 or EZH1/2 inhibitors. 20. Grade 3b FL or evidence of transformation to invasive lymphoma

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: HH2853 administered on a BID schedule in continuous 28-day treatment cycles; HH2853 is supplied as tables with dosage strength of 25mg and 200mg. HH2853 Tablet will be administered orally on a continuous twice daily (BID) schedule, on a flat scale of mg and not individually adjusted by weight or body surface area. A treatment cycle is defined as 28 days for the purposes of scheduling procedures and evaluations. All patients will be treated with HH2853 orally on a continuous BID schedule, beginning on Cycle 1 Day 1. But patients in accelerated titration (ATD) part should be administered a single dose on the first day in order to evaluate the PK of a single dose administration. Dosing is twice daily from the second day thereafter.

Drug: HH2853 Tablets; Proposed daily dose (BID): 50mg, 100mg, 200mg, 400mg, 600mg, 800mg, 1000mg. It is possible for additional and/or intermediate dose levels to be added during the course of the study. Cohorts may be added at any dose level below the MTD in order to better understand safety, PK or PD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated Dose (MTD)	Determine MTD of HH2853	28-day treatment cycles
Recommended phase II dose (RP2D)	Determine RP2D of HH2853	28-day treatment cycles
Adverse events assessed according to NCI-CTCAE V5.0	Evaluate the safety of HH2853	28-day treatment cycles
Dose limiting toxicities (DLT)	Evaluate the tolerability of HH2853	28-day treatment cycles
Objective response rate (ORR）	Assess the preliminary efficacy of HH2853	28-day treatment cycles

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClast	Characterize the pharmacokinetic profile of HH2853	28-day treatment cycles
AUCinf	Characterize the pharmacokinetic profile of HH2853	28-day treatment cycles
Cmax	Characterize the pharmacokinetic profile of HH2853	28-day treatment cycles
Tmax	Characterize the pharmacokinetic profile of HH2853	28-day treatment cycles
CL/F	Characterize the pharmacokinetic profile of HH2853	28-day treatment cycles
Vz/F	Characterize the pharmacokinetic profile of HH2853	28-day treatment cycles
Terminal half-life (T1/2)	Characterize the pharmacokinetic profile of HH2853	28-day treatment cycles
Duration of response (DoR)	Assess the preliminary efficacy of HH2853	28-day treatment cycles
Progression-free survival (PFS)	Assess the preliminary efficacy of HH2853	28-day treatment cycles
Disease control rate (DCR)	Assess the preliminary efficacy of HH2853	28-day treatment cycles
Time to response (TTR)	Assess the preliminary efficacy of HH2853	28-day treatment cycles
Time to progression (TTP)	Assess the preliminary efficacy of HH2853	28-day treatment cycles
Clinical Outcome	Explore the association between potential biomarker and the clinical outcome	28-day treatment cycles

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (ORR）	Assess the preliminary efficacy of HH2853	28-day treatment cycles
Change in tri-methylation of Histone H3K27 (H3K27me3)	Assss the pharmacodynamic response	14-day treatment
Biomarker Status	Explore the relationship between the alteration status of biomarker and treatment efficacy	28-day treatment cycles
Overall survival (OS)	Assess the preliminary efficacy of HH2853	28-day treatment cycles

Collaborators and Investigators

• Sponsor: Haihe Biopharma Co., Ltd.
• Investigators: Study Director: Fugen Li, Haihe Biopharma Co., Ltd.

Publications and helpful links

General Publications

• Fan Z, Wang J, Liu D, Shen L, Fang M, Johnson P, Tun H, Sommerhalder D, Yang J, Yang Y, Munozi J, Zhu J, Gao T, Li Z, Li X, Ma Q, Lv C, Yu S, Li F, Song Y, Gong J. Safety and efficacy of HH2853, a novel EZH1/2 dual inhibitor, in patients with refractory solid tumours or non-Hodgkin lymphomas: a phase I study. EClinicalMedicine. 2025 Aug 7;86:103398. doi: 10.1016/j.eclinm.2025.103398. eCollection 2025 Aug.
• Hong H, Chen Z, Zhang M, Peng Z, Shen J, Shuang Y, Zhou H, Guo H, Huang H, Li F, Qian Z, Liu L, Wang L, Yang W, Zhang L, He P, Qian S, Li F, Li M, Lin T. A multicenter, open-label, single-arm, phase Ib clinical trial of HH2853 treatment in patients with relapsed and/or refractory peripheral T-cell lymphoma. J Hematol Oncol. 2025 Apr 27;18(1):50. doi: 10.1186/s13045-025-01697-z.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: May 6, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 15, 2020

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: Phase I/II; HH2853; PRC2; EZH 1/2 inhibitor
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms, Connective and Soft Tissue; Lymphoma, T-Cell; Hemic and Lymphatic Diseases; Lymphoma, Follicular; Sarcoma; Lymphoma, T-Cell, Peripheral
• Other Study ID Numbers: HH2853-G101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in China, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.haihepharma.com/
• IPD Sharing Time Frame: Within six months after the approval of a new product or a new indication for an approved product in China
• IPD Sharing Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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