Evaluate the Safety and Clinical Activity of HH2853

NCT04390737 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HH2853-G101
• Study Type: interventional
• Target: 254
• Locations: 2 countries
• Sites: 25

Brief 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.

Conditions

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

Keywords

Phase I/II; HH2853; PRC2; EZH 1/2 inhibitor

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (13)

• AUClast

  28-day treatment cycles

• AUCinf

  28-day treatment cycles

• Cmax

  28-day treatment cycles

• Tmax

  28-day treatment cycles

• CL/F

  28-day treatment cycles

Other Outcomes (4)

• Overall survival (ORR）

  28-day treatment cycles

• Change in tri-methylation of Histone H3K27 (H3K27me3)

  14-day treatment

• Biomarker Status

  28-day treatment cycles

Study Arms (1)

HH2853 administered on a BID schedule in continuous 28-day treatment cycles

EXPERIMENTAL

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

HH2853 Tablets DRUG

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.

HH2853 administered on a BID schedule in continuous 28-day treatment cycles

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provided signed written informed consent prior to initiation of any study-related procedures;
• Males and females ≥ 18years of age at the time of consent are obtained (or meet the country's regulatory defined adult legal age);
• 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:
• Histologically or cytologically documented advanced recurrent or metastatic solid tumor.
• 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.)
• 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:
• Confirmed by local histology or cytology
• 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:
• Confirmed by local pathology as advanced recurrent or metastatic solid tumor.

You may not qualify if:

• 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.
• Symptomatic CNS metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease.
• Patients with prior transplant are excluded;
• Major surgery within 4 weeks prior to first dose;
• A prohibited medication or expected to require any of these medications during treatment with study drug within 2 weeks of first dose;
• 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).
• Concomitant malignancies or previous malignancies
• 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.
• Any toxicities from prior treatment that have not recovered to ≤ CTCAE Grade 1
• There were ≥ 3 lesions with punctate bleeding, any active bleeding, intratumoral bleeding, known bleeding tendencies, or treatment with antiplatelet/antithrombotic drugs.
• Gastrointestinal condition which could impair absorption of study medication;
• Psychological, familial, sociological or geographical conditions that do not permit compliance with the protocol;
• 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

Sponsors & Collaborators

• Haihe Biopharma Co., Ltd.: lead

Study Sites (25)

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

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

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

RECRUITING

Beijing Cancer Hospital

Beijing, China

RECRUITING

Sun Yat-Sen University Cancer Hospital

Guangzhou, China

RECRUITING

Related Publications (2)

• 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.

  PMID: 40821900 DERIVED

• 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.

  PMID: 40289142 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular; Sarcoma; Lymphoma, T-Cell, Peripheral

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Lymphoma, T-Cell

Study Officials

• Fugen Li

  Haihe Biopharma Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Haiyue Chen

CONTACT

+86 21 20568888; haiyue.chen@haihepharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 15, 2020
• Study Start: September 8, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in China
• 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.

Locations

CN (21); US (4)