[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT04390737":3,"trial-entities:NCT04390737":382,"trial-summary:NCT04390737":393},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":23,"study_type":28,"primary_purpose":29,"phases":30,"enrollment_info":33,"interventions":36,"primary_outcomes":43,"secondary_outcomes":60,"sex":89,"minimum_age":90,"maximum_age":91,"healthy_volunteers":92,"eligibility_criteria":93,"std_ages":97,"locations":100,"central_contacts":364,"overall_officials":369,"references":373,"see_also_links":381},"NCT04390737","HH2853-G101","Evaluate the Safety and Clinical Activity of HH2853","A Phase I\u002FII Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of HH2853 in Patients With Relapsed\u002FRefractory Non-Hodgkin's Lymphomas or Advanced Solid Tumors","RECRUITING","2028-12-31","2026-01","2026-01-30","2020-09-08","Haihe Biopharma Co., Ltd.","INDUSTRY",true,"This is an open-label, multicenter, first-in-human phase I\u002FII 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:\n\nPhase 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.\n\nEligible patients will be enrolled in the ascending dose until MTD\u002FRP2D is established.\n\nPhase 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.\n\nThe 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\u002FRP2D, and patient number at each dose level.\n\nPhase II（China Only）:\n\nPhase II is planned after the completion of phase I. Up to approximately 193 patients will be enrolled as outlined below:\n\n* Cohort 1: Relapsed\u002FRefractory FL (n≈56)\n* Cohort 2: Epithelioid sarcoma (n≈77)\n* Cohort 3: Relapsed\u002FRefractory PTCL, other relapsed\u002Frefractory 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\u002Fand SMARCA4 mutation (n≈60)",[19,20,21,22],"FL Lymphoma","Epithelioid Sarcoma","Peripheral T Cell Lymphoma","Advanced Solid Tumor",[24,25,26,27],"Phase I\u002FII","HH2853","PRC2","EZH 1\u002F2 inhibitor","INTERVENTIONAL","TREATMENT",[31,32],"PHASE1","PHASE2",{"count":34,"type":35},254,"ESTIMATED",[37],{"type":38,"name":39,"description":40,"armGroupLabels":41},"DRUG","HH2853 Tablets","Proposed daily dose (BID): 50mg, 100mg, 200mg, 400mg, 600mg, 800mg, 1000mg. It is possible for additional and\u002For 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.",[42],"HH2853 administered on a BID schedule in continuous 28-day treatment cycles",[44,48,51,54,57],{"measure":45,"description":46,"timeFrame":47},"Maximum tolerated Dose (MTD)","Determine MTD of HH2853","28-day treatment cycles",{"measure":49,"description":50,"timeFrame":47},"Recommended phase II dose (RP2D)","Determine RP2D of HH2853",{"measure":52,"description":53,"timeFrame":47},"Adverse events assessed according to NCI-CTCAE V5.0","Evaluate the safety of HH2853",{"measure":55,"description":56,"timeFrame":47},"Dose limiting toxicities (DLT)","Evaluate the tolerability of HH2853",{"measure":58,"description":59,"timeFrame":47},"Objective response rate (ORR）","Assess the preliminary efficacy of HH2853",[61,64,66,68,70,72,74,76,78,80,82,84,86],{"measure":62,"description":63,"timeFrame":47},"AUClast","Characterize the pharmacokinetic profile of HH2853",{"measure":65,"description":63,"timeFrame":47},"AUCinf",{"measure":67,"description":63,"timeFrame":47},"Cmax",{"measure":69,"description":63,"timeFrame":47},"Tmax",{"measure":71,"description":63,"timeFrame":47},"CL\u002FF",{"measure":73,"description":63,"timeFrame":47},"Vz\u002FF",{"measure":75,"description":63,"timeFrame":47},"Terminal half-life (T1\u002F2)",{"measure":77,"description":59,"timeFrame":47},"Duration of response (DoR)",{"measure":79,"description":59,"timeFrame":47},"Progression-free survival (PFS)",{"measure":81,"description":59,"timeFrame":47},"Disease control rate (DCR)",{"measure":83,"description":59,"timeFrame":47},"Time to response (TTR)",{"measure":85,"description":59,"timeFrame":47},"Time to progression (TTP)",{"measure":87,"description":88,"timeFrame":47},"Clinical Outcome","Explore the association between potential biomarker and the clinical outcome","ALL","18 Years",null,false,{"inclusion":94,"exclusion":95,"raw_text":96},[],[],"Inclusion criteria:\n\n1. Provided signed written informed consent prior to initiation of any study-related procedures;\n2. Males and females ≥ 18years of age at the time of consent are obtained (or meet the country's regulatory defined adult legal age);\n3. Tumor type criteria:\n\nThe specific requirements for specific subtypes of recurrent\u002Frefractory non Hodgkin's lymphoma (NHL) confirmed by histology are as follows:\n\nHistologically 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\u002Frefractory 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\\\u003C5), and is not a candidate for salvage treatment or autologous\u002Fallogeneic stem cell transplantation.\n\nRelapsed\u002Frefractory clinicopathologically documented PTCL with at least 1 line of prior systemic treatment (maximum \\\u003C5 lines). Solid tumors that meet the following criteria:\n\n1. Histologically or cytologically documented advanced recurrent or metastatic solid tumor.\n2. 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.)\n3. Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent. One of the following criteria should be met.\n\nPatients 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.\n\nFor epithelioid sarcoma in Phase I and Phase II cohort 2:\n\n1. Confirmed by local histology or cytology\n2. Patients with unresectable locally delayed or metastatic epithelioid sarcoma who have undergone treatment (including those who have failed treatment and developed intolerable toxicity).\n\nFor solid tumors in Phase I and Phase II queue 3:\n\n1. Confirmed by local pathology as advanced recurrent or metastatic solid tumor.\n2. 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\u002FRefractory FL, Epithelioid sarcoma, relapsed\u002Frefractory PTCL, other relapsed\u002Frefractory 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\u002Fand 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\u002FdL for patients with Gilbert's syndrome 2.AST\u002FSGOT and ALT\u002FSGPT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present 3.24-hour creatinine clearance (calculated\\* or measured value\\*\\*)≥ 50 mL\u002Fmin 4.Platelets ≥ 1 x LLN (no Platelet transfusion for 7 days prior to screening) 5.Hemoglobin (Hgb) ≥ 9 g\u002FdL 6.Absolute Neutrophil Count (ANC) ≥ 1.0 x 10\\^9\u002FL 7.Adequate coagulation function: International normalized ratio (INR) \\\u003C1.3 (or \\\u003C3.0 on anticoagulants) 9. Measurable lesion\n\nExclusion Criteria:\n\n1. 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.\n2. Symptomatic CNS metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease.\n3. Patients with prior transplant are excluded;\n4. Major surgery within 4 weeks prior to first dose;\n5. A prohibited medication or expected to require any of these medications during treatment with study drug within 2 weeks of first dose;\n6. 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\u002FmL; HCV antibody test results are positive, and HCV (hepatitis C virus) RNA PCR test results are positive).\n7. Concomitant malignancies or previous malignancies\n8. 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.\n9. Any toxicities from prior treatment that have not recovered to ≤ CTCAE Grade 1\n10. There were ≥ 3 lesions with punctate bleeding, any active bleeding, intratumoral bleeding, known bleeding tendencies, or treatment with antiplatelet\u002Fantithrombotic drugs.\n11. Gastrointestinal condition which could impair absorption of study medication;\n12. Psychological, familial, sociological or geographical conditions that do not permit compliance with the protocol;\n13. Cardiac exclusion criteria:\n\n1.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) \\\u003C 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\u002F2 inhibitors. 20. Grade 3b FL or evidence of transformation to invasive lymphoma",[98,99],"ADULT","OLDER_ADULT",[101,111,118,125,133,146,158,167,174,188,201,215,228,241,252,263,270,281,292,299,310,323,339,352,358],{"facility":102,"status":103,"city":104,"state":105,"zip":106,"country":107,"geoPoint":108},"Mayo Clinic","COMPLETED","Phoenix","Arizona","85054","United States",{"lat":109,"lon":110},33.44838,-112.07404,{"facility":102,"status":103,"city":112,"state":113,"zip":114,"country":107,"geoPoint":115},"Jacksonville","Florida","32224",{"lat":116,"lon":117},30.33218,-81.65565,{"facility":102,"status":103,"city":119,"state":120,"zip":121,"country":107,"geoPoint":122},"Rochester","Minnesota","55905",{"lat":123,"lon":124},44.02163,-92.4699,{"facility":126,"status":103,"city":127,"state":128,"zip":129,"country":107,"geoPoint":130},"NEXT Oncology","San Antonio","Texas","78240",{"lat":131,"lon":132},29.42412,-98.49363,{"facility":134,"status":8,"city":135,"state":136,"country":137,"contacts":138,"geoPoint":143},"The First Affiliated Hospital of Anhui Medical University","Hefei","Anhui","China",[139],{"name":140,"role":141,"email":142},"Kangsheng Gu","CONTACT","13805692145@163.com",{"lat":144,"lon":145},31.86389,117.28083,{"facility":147,"status":8,"city":148,"state":149,"zip":150,"country":137,"contacts":151,"geoPoint":155},"Beijing Cancer Hospital","Beijing","Beijing Municipality","100142",[152],{"name":153,"role":141,"email":154},"Lin Shen","linshenpku@163.com",{"lat":156,"lon":157},39.9075,116.39723,{"facility":147,"status":8,"city":148,"state":149,"country":137,"contacts":159,"geoPoint":166},[160,163],{"name":161,"role":141,"email":162},"Jun Zhu","zhujun3346@163.com",{"name":164,"role":141,"email":165},"Yuqin Song","songyuqin622@163.com",{"lat":156,"lon":157},{"facility":168,"status":8,"city":148,"state":149,"country":137,"contacts":169,"geoPoint":173},"Beijing Jishuitan Hospital",[170],{"name":171,"role":141,"email":172},"Xiaohui Niu","niuxiaohui@263.net",{"lat":156,"lon":157},{"facility":175,"status":8,"city":176,"state":177,"country":137,"contacts":178,"geoPoint":185},"Sun Yat-Sen University Cancer Hospital","Guangzhou","Guangdong",[179,182],{"name":180,"role":141,"email":181},"Zhiming Li","lizhm@sysucc.org.cn",{"name":183,"role":184},"Jundong Li","PRINCIPAL_INVESTIGATOR",{"lat":186,"lon":187},23.11667,113.25,{"facility":189,"status":8,"city":190,"state":191,"country":137,"contacts":192,"geoPoint":198},"Affiliated Tumor Hospital of Guangxi Medical University","Nanning","Guangxi",[193,196],{"name":194,"role":141,"email":195},"Hong Cen","cen_hong@163.com",{"name":197,"role":184},"Weimin Xie",{"lat":199,"lon":200},22.81667,108.31667,{"facility":202,"status":8,"city":203,"state":204,"country":137,"contacts":205,"geoPoint":212},"Henan Cancer Hospital","Zhengzhou","Henan",[206,209],{"name":207,"role":141,"email":208},"Keshu Zhou","drzhouks77@163.com",{"name":210,"role":141,"email":211},"Weitao Yao","ywtwhm@163.com",{"lat":213,"lon":214},34.75778,113.64861,{"facility":216,"status":8,"city":217,"state":218,"country":137,"contacts":219,"geoPoint":225},"Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","Wuhan","Hubei",[220,223],{"name":221,"role":141,"email":222},"Liling Zhang","zlladct@163.com",{"name":224,"role":184},"Jing Chen",{"lat":226,"lon":227},30.58333,114.26667,{"facility":229,"status":8,"city":230,"state":231,"country":137,"contacts":232,"geoPoint":238},"Hunan Cancer Hospital","Changsha","Hunan",[233,236],{"name":234,"role":141,"email":235},"Hui Zhou","Zhouhui9403@126.com",{"name":237,"role":184},"Xianan Li",{"lat":239,"lon":240},28.19874,112.97087,{"facility":242,"status":8,"city":243,"state":244,"country":137,"contacts":245,"geoPoint":249},"Affiliated Drum Tower Hospital, Medical School of Nanjing University","Nanjing","Jiangsu",[246],{"name":247,"role":141,"email":248},"Tianru Li","li_rutian@163.com",{"lat":250,"lon":251},32.06167,118.77778,{"facility":253,"status":8,"city":254,"state":255,"country":137,"contacts":256,"geoPoint":260},"Liaoning Cancer Hospital&Institute","Shenyang","Liaoning",[257],{"name":258,"role":141,"email":259},"Xiaojing Zhang","Zhangxiaojingwu@163.com",{"lat":261,"lon":262},41.79222,123.43278,{"facility":264,"status":8,"city":254,"state":255,"country":137,"contacts":265,"geoPoint":269},"Shengjing Hospital Of China Medical University",[266],{"name":267,"role":141,"email":268},"Wei Yang","sjyangw@163.com",{"lat":261,"lon":262},{"facility":271,"status":8,"city":272,"state":273,"country":137,"contacts":274,"geoPoint":278},"Linyi Tumor Hospital","Linyi","Shandong",[275],{"name":276,"role":141,"email":277},"Zhen Wang","LYSZLYYNSK@163.com",{"lat":279,"lon":280},35.06306,118.34278,{"facility":282,"status":8,"city":283,"state":284,"country":137,"contacts":285,"geoPoint":289},"Shanghai Sixth People's Hospital","Shanghai","Shanghai Municipality",[286],{"name":287,"role":141,"email":288},"Yang Dong","dongyang6405@163.com",{"lat":290,"lon":291},31.22222,121.45806,{"facility":293,"status":8,"city":283,"state":284,"country":137,"contacts":294,"geoPoint":298},"Zhongshan Hospital Fudan University",[295],{"name":296,"role":141,"email":297},"Yuhong Zhou","zhou.yuhong@zs-hospital.sh.cn",{"lat":290,"lon":291},{"facility":300,"status":8,"city":301,"state":302,"country":137,"contacts":303,"geoPoint":307},"Shanxi Cancer Hospital","Taiyuan","Shanxi",[304],{"name":305,"role":141,"email":306},"Yuxia Shi","1274174089@qq.com",{"lat":308,"lon":309},37.86944,112.56028,{"facility":311,"status":8,"city":312,"state":313,"country":137,"contacts":314,"geoPoint":320},"West China Hospital of Sichuan University","Chengdu","Sichuan",[315,318],{"name":316,"role":141,"email":317},"Lijun Zou","hxlcyxy@163.com",{"name":319,"role":141},"Yu Jiang",{"lat":321,"lon":322},30.66667,104.06667,{"facility":324,"status":8,"city":325,"state":326,"country":137,"contacts":327,"geoPoint":336},"Tianjin Cancer Hospital","Tianjin","Tianjin Municipality",[328,331,333,335],{"name":329,"role":141,"email":330},"Shiyong Zhou","zsy1003@163.com",{"name":332,"role":184},"Jilong Yang",{"name":334,"role":184},"Yun Yang",{"name":329,"role":184},{"lat":337,"lon":338},39.14222,117.17667,{"facility":340,"status":8,"city":341,"state":342,"country":137,"contacts":343,"geoPoint":349},"Zhejiang Cancer Hospital","Hangzhou","Zhejiang",[344,347],{"name":345,"role":141,"email":346},"Meiyu Fang","fangmy@zjcc.org.cn",{"name":348,"role":184},"Haiyan Yang",{"lat":350,"lon":351},30.29365,120.16142,{"facility":147,"status":8,"city":148,"country":137,"contacts":353,"geoPoint":357},[354],{"name":355,"role":141,"email":356},"Zhengfu Fan","zhengfufan@126.com",{"lat":156,"lon":157},{"facility":175,"status":8,"city":176,"country":137,"contacts":359,"geoPoint":363},[360],{"name":361,"role":141,"email":362},"Jin Wang","wangjinr@sysucc.org.cn",{"lat":186,"lon":187},[365],{"name":366,"role":141,"phone":367,"email":368},"Haiyue Chen","+86 21 20568888","haiyue.chen@haihepharma.com",[370],{"name":371,"affiliation":13,"role":372},"Fugen Li","STUDY_DIRECTOR",[374,378],{"pmid":375,"type":376,"citation":377},"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\u002F2 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\u002Fj.eclinm.2025.103398. eCollection 2025 Aug.",{"pmid":379,"type":376,"citation":380},"40289142","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\u002For refractory peripheral T-cell lymphoma. J Hematol Oncol. 2025 Apr 27;18(1):50. doi: 10.1186\u002Fs13045-025-01697-z.",[],{"nct_id":4,"conditions":383,"biomarkers":388},[384,20,385,386,387],"Diffuse Large B-Cell Lymphoma","Follicular Lymphoma","Peripheral T-Cell Lymphoma, Not Otherwise Specified","Solid Neoplasm",[389,390,391,392],"AT-Rich Interactive Domain-Containing Protein 1A","BAP1 Gene","SWI\u002FSNF-Related Matrix-Associated Actin-Dependent Regulator of Chromatin Subfamily B Member 1","Transcription Activator BRG1",{"nct_id":4,"found":15,"summary":394,"prompt_version":404},{"design":395,"status":396,"heading":397,"summary":398,"follow_up":399,"word_count":400,"commitments":401,"compensation":402,"drugs_mentioned":403},"This is an open-label (meaning everyone knows what treatment is being given), multi-center, first-in-human study with three parts: dose escalation, dose extension, and Phase II. It plans to enroll 254 participants.","completed","HH2853 for Lymphoma and Advanced Solid Tumors","This study is testing a drug called HH2853 in people with certain types of lymphoma (FL Lymphoma, Peripheral T Cell Lymphoma) and advanced solid tumors. The main goals are to find the safest and most effective dose of HH2853, and to understand any side effects. HH2853 is given as tablets twice a day. The study is open to adults aged 18 and older. It's a multi-part study, starting with finding the right dose and then expanding to learn more about how well it works and its safety. The study aims to enroll 254 participants, but its current status is unclear.","Safety and dose-related outcomes are measured during 28-day treatment cycles.",100,"You would take HH2853 tablets twice daily in continuous 28-day treatment cycles. Safety and side effects will be checked during these cycles.","Not stated in the trial record.",[],"v2"]