Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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:
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| AUClast | Characterize the pharmacokinetic profile of HH2853 | 28-day treatment cycles |
| AUCinf | Characterize the pharmacokinetic profile of HH2853 |
| 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 |
Inclusion 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:
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:
For solid tumors in Phase I and Phase II queue 3:
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
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Haiyue Chen | Contact | +86 21 20568888 | haiyue.chen@haihepharma.com |
| Name | Affiliation | Role |
|---|---|---|
| Fugen Li | Haihe Biopharma Co., Ltd. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Completed | Phoenix | Arizona | 85054 | United States | |
| Mayo Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40821900 | Derived | 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. | |
| 40289142 |
Not provided
Not provided
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/
Within six months after the approval of a new product or a new indication for an approved product in China
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 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 |
| 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 |
| Completed |
| Jacksonville |
| Florida |
| 32224 |
| United States |
| Mayo Clinic | Completed | Rochester | Minnesota | 55905 | United States |
| NEXT Oncology | Completed | San Antonio | Texas | 78240 | United States |
| The First Affiliated Hospital of Anhui Medical University | Recruiting | Hefei | Anhui | China |
|
| Beijing Cancer Hospital | Recruiting | Beijing | Beijing Municipality | 100142 | China |
|
| Beijing Cancer Hospital | Recruiting | Beijing | Beijing Municipality | China |
|
| Beijing Jishuitan Hospital | Recruiting | Beijing | Beijing Municipality | China |
|
| Sun Yat-Sen University Cancer Hospital | Recruiting | Guangzhou | Guangdong | China |
|
| Affiliated Tumor Hospital of Guangxi Medical University | Recruiting | Nanning | Guangxi | China |
|
| Henan Cancer Hospital | Recruiting | Zhengzhou | Henan | China |
|
| Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Recruiting | Wuhan | Hubei | China |
|
| Hunan Cancer Hospital | Recruiting | Changsha | Hunan | China |
|
| Affiliated Drum Tower Hospital, Medical School of Nanjing University | Recruiting | Nanjing | Jiangsu | China |
|
| Liaoning Cancer Hospital&Institute | Recruiting | Shenyang | Liaoning | China |
|
| Shengjing Hospital Of China Medical University | Recruiting | Shenyang | Liaoning | China |
|
| Linyi Tumor Hospital | Recruiting | Linyi | Shandong | China |
|
| Shanghai Sixth People's Hospital | Recruiting | Shanghai | Shanghai Municipality | China |
|
| Zhongshan Hospital Fudan University | Recruiting | Shanghai | Shanghai Municipality | China |
|
| Shanxi Cancer Hospital | Recruiting | Taiyuan | Shanxi | China |
|
| West China Hospital of Sichuan University | Recruiting | Chengdu | Sichuan | China |
|
| Tianjin Cancer Hospital | Recruiting | Tianjin | Tianjin Municipality | China |
|
| Zhejiang Cancer Hospital | Recruiting | Hangzhou | Zhejiang | China |
|
| Beijing Cancer Hospital | Recruiting | Beijing | China |
|
| Sun Yat-Sen University Cancer Hospital | Recruiting | Guangzhou | China |
|
| 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. |
| ID | Term |
|---|---|
| D008224 | Lymphoma, Follicular |
| D012509 | Sarcoma |
| D016411 | Lymphoma, T-Cell, Peripheral |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D016399 | Lymphoma, T-Cell |
Not provided
Not provided