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RecruitingNCT04390737Updated Jan 30, 2026

Evaluate the Safety and Clinical Activity of HH2853

A Phase 1/2 interventional study of HH2853 Tablets in FL Lymphoma, Epithelioid Sarcoma and Peripheral T Cell Lymphoma, sponsored by Haihe Biopharma Co., Ltd.. Recruiting at 25 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-30.

Sponsored by Haihe Biopharma Co., Ltd. · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
254
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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)
02

Conditions studied

  • FL Lymphoma
  • Epithelioid Sarcoma
  • Peripheral T Cell Lymphoma
  • Advanced Solid Tumor

Keywords

  • Phase I/II
  • HH2853
  • PRC2
  • EZH 1/2 inhibitor
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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

04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
254 participants (estimated)

Study arms

  • 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

Interventions

  • DrugHH2853 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.

05

What researchers measure

Primary outcomes

  1. Maximum tolerated Dose (MTD)

    Determine MTD of HH2853

    Time frame: 28-day treatment cycles

  2. Recommended phase II dose (RP2D)

    Determine RP2D of HH2853

    Time frame: 28-day treatment cycles

  3. Adverse events assessed according to NCI-CTCAE V5.0

    Evaluate the safety of HH2853

    Time frame: 28-day treatment cycles

  4. Dose limiting toxicities (DLT)

    Evaluate the tolerability of HH2853

    Time frame: 28-day treatment cycles

  5. Objective response rate (ORR)

    Assess the preliminary efficacy of HH2853

    Time frame: 28-day treatment cycles

Secondary outcomes

  1. AUClast

    Characterize the pharmacokinetic profile of HH2853

    Time frame: 28-day treatment cycles

  2. AUCinf

    Characterize the pharmacokinetic profile of HH2853

    Time frame: 28-day treatment cycles

  3. Cmax

    Characterize the pharmacokinetic profile of HH2853

    Time frame: 28-day treatment cycles

  4. Tmax

    Characterize the pharmacokinetic profile of HH2853

    Time frame: 28-day treatment cycles

  5. CL/F

    Characterize the pharmacokinetic profile of HH2853

    Time frame: 28-day treatment cycles

  6. Vz/F

    Characterize the pharmacokinetic profile of HH2853

    Time frame: 28-day treatment cycles

  7. Terminal half-life (T1/2)

    Characterize the pharmacokinetic profile of HH2853

    Time frame: 28-day treatment cycles

  8. Duration of response (DoR)

    Assess the preliminary efficacy of HH2853

    Time frame: 28-day treatment cycles

  9. Progression-free survival (PFS)

    Assess the preliminary efficacy of HH2853

    Time frame: 28-day treatment cycles

  10. Disease control rate (DCR)

    Assess the preliminary efficacy of HH2853

    Time frame: 28-day treatment cycles

  11. Time to response (TTR)

    Assess the preliminary efficacy of HH2853

    Time frame: 28-day treatment cycles

  12. Time to progression (TTP)

    Assess the preliminary efficacy of HH2853

    Time frame: 28-day treatment cycles

  13. Clinical Outcome

    Explore the association between potential biomarker and the clinical outcome

    Time frame: 28-day treatment cycles

Other outcomes

  1. Overall survival (ORR)

    Assess the preliminary efficacy of HH2853

    Time frame: 28-day treatment cycles

  2. Change in tri-methylation of Histone H3K27 (H3K27me3)

    Assss the pharmacodynamic response

    Time frame: 14-day treatment

  3. Biomarker Status

    Explore the relationship between the alteration status of biomarker and treatment efficacy

    Time frame: 28-day treatment cycles

  4. Overall survival (OS)

    Assess the preliminary efficacy of HH2853

    Time frame: 28-day treatment cycles

06

Study locations

21 of 25 sites recruiting
  • Mayo Clinic
    Phoenix, Arizona 85054, United States
    Completed
  • Mayo Clinic
    Jacksonville, Florida 32224, United States
    Completed
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
    Completed
  • NEXT Oncology
    San Antonio, Texas 78240, United States
    Completed
  • The First Affiliated Hospital of Anhui Medical University
    Hefei, Anhui, China
    Recruiting
  • Beijing Cancer Hospital
    Beijing, Beijing Municipality 100142, China
    Recruiting
  • Beijing Cancer Hospital
    Beijing, Beijing Municipality, China
    Recruiting
  • Beijing Jishuitan Hospital
    Beijing, Beijing Municipality, China
    Recruiting
  • Sun Yat-Sen University Cancer Hospital
    Guangzhou, Guangdong, China
    Recruiting
  • Affiliated Tumor Hospital of Guangxi Medical University
    Nanning, Guangxi, China
    Recruiting
  • Henan Cancer Hospital
    Zhengzhou, Henan, China
    Recruiting
  • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
    Wuhan, Hubei, China
    • Liling Zhang · Contact · zlladct@163.com
    • Jing Chen · Principal investigator
    Recruiting
  • Hunan Cancer Hospital
    Changsha, Hunan, China
    Recruiting
  • Affiliated Drum Tower Hospital, Medical School of Nanjing University
    Nanjing, Jiangsu, China
    Recruiting
  • Liaoning Cancer Hospital&Institute
    Shenyang, Liaoning, China
    Recruiting
  • Shengjing Hospital Of China Medical University
    Shenyang, Liaoning, China
    Recruiting
  • Linyi Tumor Hospital
    Linyi, Shandong, China
    Recruiting
  • Shanghai Sixth People's Hospital
    Shanghai, Shanghai Municipality, China
    Recruiting
  • Zhongshan Hospital Fudan University
    Shanghai, Shanghai Municipality, China
    Recruiting
  • Shanxi Cancer Hospital
    Taiyuan, Shanxi, China
    Recruiting
  • West China Hospital of Sichuan University
    Chengdu, Sichuan, China
    Recruiting
  • Tianjin Cancer Hospital
    Tianjin, Tianjin Municipality, China
    • Shiyong Zhou · Contact · zsy1003@163.com
    • Jilong Yang · Principal investigator
    • Yun Yang · Principal investigator
    • Shiyong Zhou · Principal investigator
    Recruiting
  • Zhejiang Cancer Hospital
    Hangzhou, Zhejiang, China
    Recruiting
  • Beijing Cancer Hospital
    Beijing, China
    Recruiting
  • Sun Yat-Sen University Cancer Hospital
    Guangzhou, China
    Recruiting
07

References and documents

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. PubMed 40821900 ↗
  • 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. PubMed 40289142 ↗

Individual participant data

Plan to share: Yes — 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/

Supporting information: Study protocol

08

Registry details

Key details

Study ID
NCT04390737
Lead sponsor
Haihe Biopharma Co., Ltd.
Responsible party
Sponsor
First posted
May 15, 2020
Start date
Sep 8, 2020
Primary completion
Dec 31, 2027 (estimated)
Completion
Dec 31, 2028 (estimated)
Last update
Jan 30, 2026

Study contacts

Haiyue Chen
Contact
haiyue.chen@haihepharma.com
+86 21 20568888
Fugen Li
study director · Haihe Biopharma Co., Ltd.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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