Compare Efficacy, Safety and Immunogenicity of HLX02 and Herceptin in Previously Untreated HER2 +Overexpressing Metastatic Breast Cancer
Double-blind, Randomized, Multicenter, Phase III Clinical Study to Compare the Efficacy and to Evaluate the Safety and Immunogenicity of Trastuzumab Biosimilar HLX02 and EU-sourced Herceptin® in Previously Untreated HER2 Overexpressing Metastatic Breast Cancer
2 other identifiers
interventional
652
3 countries
88
Brief Summary
This is a Phase III, double-blind, randomized multicenter study to compare the efficacy and to evaluate the safety and immunogenicity of HLX02 and European Union (EU)-sourced Herceptin® in patients with human epidermal growth factor receptor 2 (HER2)-positive, locally recurrent or previously untreated metastatic breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 breast-cancer
Started Nov 2016
88 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2016
CompletedFirst Submitted
Initial submission to the registry
March 14, 2017
CompletedFirst Posted
Study publicly available on registry
March 20, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 23, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 28, 2021
CompletedResults Posted
Study results publicly available
May 17, 2024
CompletedMay 17, 2024
April 1, 2024
2.1 years
March 14, 2017
December 20, 2022
April 27, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
ORR 24
calculated as the proportion of patients with a best response of complete response (CR) or partial response (PR) from first assessment until Week 24 according to RECIST 1.1 by central imaging review (CIR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions,Complete Response (CR): Disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm, Partial Response (PR): At least a 30% decrease in the sum ofdiameters of target lesions, taking as reference thebaseline sum diameters.Overall Response (OR) = CR + PR.
From time of First treatment to week 24
Secondary Outcomes (5)
DoR
Up to 2 years
DCR
Up to 2 years
CBR
Up to 2 years
Median PFS up to 12 Months
From time of first treatment to 12 months
Overall Survival at 12, 24, and 36 Months
From time of first treatment to 36 months
Study Arms (2)
HLX02+Docetaxel
EXPERIMENTALHLX02+Docetaxel
Herceptin®+Docetaxel
ACTIVE COMPARATORHerceptin®+Docetaxel
Interventions
8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles.
8 mg/kg administered intravenously over 90 minutes as a loading dose on Day 1, Cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles
75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle
Eligibility Criteria
You may qualify if:
- Patients have voluntarily agreed to participate and given written informed consent.
- Male or female ≥18 years of age on day of signing the informed consent form (ICF).
- Histologically or cytologically confirmed adenocarcinoma of the breast.
- Recurrent disease not amenable to curative surgery or radiation therapy, or metastatic disease with an indication for a taxane-containing therapy.
- Availability of formalin-fixed paraffin-embedded (FFPE) tissue block from the primary tumor, or a metastatic lesion, to confirm HER2-positivity by the central laboratory, based on FISH amplification ratio ≥2.0 or IHC score 3+, and for hormone status (ER/PgR) determination (local or central laboratory). If not possible, a fresh biopsy is required.
- No prior systemic anticancer agent such as chemotherapy, biological or targeted agent for metastatic disease with the exception of hormonal therapy, which must be stopped at least 2 weeks before randomization. Use of herbal remedies or traditional Chinese medicines for anticancer, hematologic or liver function, or anti-infective treatment must be stopped at the time of the ICF signature (at least 2 weeks before randomization).
- For patients with recurrent disease, prior neo-/adjuvant therapy containing trastuzumab and/or lapatinib must have been stopped at least 12 months before the diagnosis of recurrent (local or metastatic) disease. If trastuzumab/lapatinib was not used, prior neo-/adjuvant therapy with a taxane must have been stopped at least 6 months before the diagnosis of recurrent (local or metastatic) disease. If only other cytotoxics were given, they must be stopped at least 4 weeks before randomization. Any hormonal therapy must be stopped at the time of the ICF signature.
- Measurable disease (at least one measurable target lesion assessed by CIR; bone-only or central nervous system \[CNS\]-only metastases are not allowed).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- LVEF within institutional range of normal at baseline (within 42 days before randomization) as determined by either echocardiography (ECHO) or multigated acquisition (MUGA) scan.
- Adequate hematologic, hepatic and renal function as indicated by the following laboratory values:
- Absolute neutrophil count (ANC) ≥1,500/μL without granulocyte-colony stimulating factor (G-CSF) or other medical support
- Platelets ≥100,000/μL
- Hemoglobin ≥9 g/dL without transfusion or other medical support within 14 days
- Serum creatinine ≤1.5 x upper limit of normal (ULN) and creatinine clearance rate ≥50 mL/min, calculated according to Cockroft-Gault formula
- +6 more criteria
You may not qualify if:
- Previously- or currently-treated (systemic chemotherapy, biological, or targeted agent, or any other anticancer agent) metastatic breast cancer with the exception of hormonal therapy.
- Participation in another clinical study within 4 weeks before enrollment (3 months for studies involving monoclonal therapy) or the intention of participating in another clinical study during any part of the study period.
- History of other malignancy within the last 5 years, except for carcinoma in-situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent.
- Known history of human immunodeficiency virus (HIV). Clinically significant active infection requiring therapy; positive tests for hepatitis B; or hepatitis C.
- Underlying medical conditions or current severe, uncontrolled systemic disease that, in the Investigator's opinion, will make the administration of study drug hazardous. A major surgical procedure within 4 weeks prior to enrollment or anticipation of the need for major surgery during the course of study.
- Current uncontrolled hypertension (systolic \>150 mmHg and/or diastolic \>100 mmHg) or unstable angina.
- History of chronic heart failure based on any New York Heart Association (NYHA) criteria, or left ventricular hypertrophy. Current serious cardiac arrhythmia requiring treatment or clinically significant conduction defects as seen on electrocardiogram (ECG). History of myocardial infarction within 6 months of randomization. History of LVEF decline to below 50% during or after previous trastuzumab neo-adjuvant or adjuvant therapy. Significant cardiac murmurs either on examination or ECHO.
- History of prior exposure to doxorubicin \>360 mg/m² (or equivalent). Use of oral, injected or implanted hormonal methods of contraception. Chronic daily use of corticoids (equivalent to \>10 mg/day methylprednisolone) by oral intake (inhalation is permitted).
- Known hypersensitivity to any of the study drugs.
- Residual non-hematologic toxicity ≥ Grade 2 from prior therapy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (88)
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, China
The Second Hospital of Anhui Medical University
Hefei, Anhui, China
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Chongqing University Cancer Hospital
Chongqing, Chongqing Municipality, China
Fujian Cancer Hospital
Fuzhou, Fujian, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, China
The First Affiliated Hospital of Xiamen University
Xiamen, Fujian, China
Affiliated Cancer Hospital and Institute of Guangzhou Medical University
Guangzhou, Guangdong, China
First Affiliated Hospital of Guangzhou University of TMC
Guangzhou, Guangdong, China
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Guangzhou, Guangdong, China
Sun Yat-sen University, Cancer Center
Guanzhou, Guangdong, China
The University of Hong Kong-Shenzhen Hospital
Shenzhen, Guangdong, China
Affiliated Hospital of Guangdong Medical University
Zhanjiang, Guangdong, China
Liuzhou General Hospital
Liuchow, Guangxi, China
Affiliated Hospital of Hebei University
Baoding, Hebei, China
Hebei Cangzhou Central Hospital
Cangzhou, Hebei, China
The Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
Henan Cancer Hospital
Zhengzhou, Henan, China
The 2nd Xiangya Hospital of Central South University
Changsha, Hu'nan, China
Hubei Cancer Hospital
Wuhan, Hubei, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
Wuhan, Hubei, China
The Third Xiangya Hospital of Central South University
Changsha, Hunan, China
Jiangsu Cancer Hospital
Nanjing, Jiangsu, China
Jiangsu Province Hospital
Nanjing, Jiangsu, China
Nanjing Bayi Hospital
Nanjing, Jiangsu, China
The Affiliated Drum Tower Hospital of Nanjing University
Nanjing, Jiangsu, China
Nantong Tumor Hospital
Nantong, Jiangsu, China
Wuxi 4th People's Hospital
Wuxi, Jiangsu, China
Xuzhou Central Hospital
Xuzhou, Jiangsu, China
Northern Jiangsu People's Hospital
Yangzhou, Jiangsu, China
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China
Jilin Cancer Hospital
Changchun, Jilin, China
Jilin Province People's Hospital
Changchun, Jilin, China
The First Hospital of Jilin University
Changchun, Jilin, China
The Second Hospital of Dalian Medical University
Dalian, Liaoning, China
General Hospital of the Northern Theater of the Chinese People's Liberation Army
Shenyang, Liaoning, China
Liaoning Cancer Hospital & Institute
Shenyang, Liaoning, China
The First Hospital of China Medical University
Shenyang, Liaoning, China
Affiliated Hospital of Qinghai University
Xining, Qinghai, China
Affiliated Hospital of Jining Medical University
Jining, Shandong, China
Jinan Central Hospital
Jinan, Shangdong, China
Yantai Yuhuangding Hospital
Yantai, Shangdong, China
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
Ruijin Hospital of Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, China
Shannxi Provincial Tumor Hospital
Xi'an, Shangxi, China
The 2nd Hospital of Xi'An Jiaotong University
Xi’an, Shanxi, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi, China
West China Hospital, Sichuan University
Chengdu, Sichuan, China
Nanchong Central Hospital
Nanchong, Sichuan, China
Tianjin Medical University Cancer Institute & Hospital
Tianjing, Tianjing, China
Yunnan Cancer Hospital
Kunming, Yunnan, China
Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
Hangzhou, Zhejiang, China
The First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou, Zhejiang, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, China
Beijing Cancer Hospital
Beijing, China
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, China
Chinese PLA General Hospital
Beijing, China
Peking Union Medical College Hospital
Beijing, China
Metro Davao Medical and Research Center, Inc.
Davao City, Davao Region, 8000, Philippines
Cardinal Santos Medical Center
San Juan City, La Union, 1502, Philippines
Manila Doctors Hospital
Manila, National Capital Region, 1000, Philippines
The Medical City
Pasig, National Capital Region, 1605, Philippines
Cebu Doctors University Hospital
Cebu City, 6000, Philippines
CI Kryvyi Rih Oncological Dispensary of DRC
Kryvyi Rih, Dnepropetrovsk, 50048, Ukraine
CNE"City Clin Hosp#4"of Dnipro City Council Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
Dnipro, Dnipropetrovsk Oblast, 49102, Ukraine
CI Carpathian Clinical Oncological Center
Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018, Ukraine
CNE CCCH of Uzh CC Oncological Center, Ther Dept, SHEI UNU
Uzhhorod, Outer Carpathian, 88000, Ukraine
Transcarpathian Regional Clinical Oncological Dispensary
Uzhhorod, Outer Carpathian, 88014, Ukraine
Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council
Lutsk, Warren, 43018, Ukraine
CTPI Chernihiv Regional Oncological Dispensary
Chernihiv, 14029, Ukraine
CI Chernivtsi RC Oncological Dispensary
Chernivtsi, 58013, Ukraine
Communal Non-profit Enterprise Regional Center of Oncology
Kharkiv, 61070, Ukraine
CI of Kherson Reg Council Kherson Regional Oncologic Dispensary
Kherson, 73000, Ukraine
Khmelnytskyi Regional Oncological Dispensary
Khmelnytskyi, 29000, Ukraine
Treatment-Diagnostic Center of Private Enterprise of PPC Atsynus
Kropyvnytskyi, 25006, Ukraine
National Institute of Cancer
Kyiv, 03022, Ukraine
CNE Kyiv City Clin Oncological Center of Ex Body of Kyiv CC(KCSA)
Kyiv, 03115, Ukraine
Kyiv Сity Clinical Oncological Center
Kyiv, 03115, Ukraine
CI of LRC Lviv Oncological Regional Treatment and Diagnostic Center
Lviv, 79031, Ukraine
CI Odesa Regional Clinical Hospital
Odesa, 65025, Ukraine
Odesa Regional Oncologic Dispensary
Odesa, 65055, Ukraine
Poltava Reg Cl Onc Dispensary of PRC Chemotherapy Dept HSEI of Ukr UMSA
Poltava, 36011, Ukraine
RCI Sumy Regional Clinical Oncological Dispensary Dept of of Chemotherapy Sumy SU
Sumy, 40022, Ukraine
Podilskyi Regional Oncological Center
Vinnytsia, 21029, Ukraine
CI Zaporizhzhia RC Onc Dispensary of ZRC Dept of Breast Pathology SI Zaporizhzhia MA of PGE of MoHU
Zaporizhzhia, 69040, Ukraine
CI Zaporizhzhia Regional Clinical Oncological Dispensary of ZRC
Zaporizhzhia, 69040, Ukraine
Related Publications (2)
Xu B, Zhang Q, Sun T, Li W, Teng Y, Hu X, Bondarenko I, Adamchuk H, Zhang L, Trukhin D, Wang S, Zheng H, Tong Z, Shparyk Y, Yang F, Yu H, Li J, Wang Q, Zhu J; HLX02-BC01 Investigators. Updated efficacy and safety of HLX02 versus reference trastuzumab in metastatic HER2-positive breast cancer: A randomized phase III equivalence trial. Breast. 2025 Apr;80:104413. doi: 10.1016/j.breast.2025.104413. Epub 2025 Feb 4.
PMID: 39954568DERIVEDXu B, Zhang Q, Sun T, Li W, Teng Y, Hu X, Bondarenko I, Adamchuk H, Zhang L, Trukhin D, Wang S, Zheng H, Tong Z, Shparyk Y, Wang Q; HLX02-BC01 Investigators. Efficacy, Safety, and Immunogenicity of HLX02 Compared with Reference Trastuzumab in Patients with Recurrent or Metastatic HER2-Positive Breast Cancer: A Randomized Phase III Equivalence Trial. BioDrugs. 2021 May;35(3):337-350. doi: 10.1007/s40259-021-00475-w. Epub 2021 Apr 7.
PMID: 33826080DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Head of Clinical Development
- Organization
- Shanghai Henlius Biotech
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 14, 2017
First Posted
March 20, 2017
Study Start
November 1, 2016
Primary Completion
November 23, 2018
Study Completion
September 28, 2021
Last Updated
May 17, 2024
Results First Posted
May 17, 2024
Record last verified: 2024-04