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Breast CancerPhase 3NCT03084237

Compare Efficacy, Safety and Immunogenicity of HLX02 and Herceptin in Previously Untreated HER2 +Overexpressing Metastatic Breast Cancer

A Phase 3 study testing HLX02, Herceptin® and docetaxel in people with Breast Cancer, run by Shanghai Henlius Biotech at 88 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
HLX02, Herceptin® and docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
652 participants
Where
88 sitesin 3 countries
Study dates
Nov 2016to 28 Sep 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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
  • Serum total bilirubin ≤1.5 x ULN (unless the patient has documented ·Gilbert's syndrome) without any medical support within 14 days
  • Serum aspartate aminotransferase/glutamicoxaloacetic transaminase (AST/SGOT) or serum alanine aminotransferase/glutamate-pyruvate transaminase (ALT/SGPT) ≤2.5 x ULN (≤5 x ULN in the case of liver metastases) provided alkaline phosphatase (ALK) is ≤2.5 x ULN. In the case of bone metastasis, serum ALK can be >2.5 x ULN if AST and ALT are ≤1.5 x ULN without any medical support within 14 days
  • International normalized ratio (INR), and activated partial prothrombin time (aPTT) or partial prothrombin time (PTT) ≤1.5 x ULN.
  • Estimated life expectancy ≥3 months.
  • Female patients are eligible to enter and participate in the study if they are of: Non-childbearing potential. Childbearing potential, have a negative serum pregnancy test at Screening, are not breast feeding, and use highly-effective or acceptable contraceptive measures before study entry and throughout the study until 7 months after the last investigational/comparator product administration. Highly-effective or acceptable contraceptive measures.
  • Male patients with partners of childbearing potential are eligible to enter and participate in the study if they, and their female partners, are willing to use highly-effective or acceptable contraceptive measures before study entry and throughout the study until 7 months after the last investigational/comparator product administration.

Who cannot join

  • Previously- or currently-treated (systemic chemotherapy, biological, or targeted agent, or any other anticancer agent) metastatic breast cancer with the exception of hormonal therapy.
  • Known brain metastasis or other CNS metastasis that is either symptomatic or untreated. Central nervous system metastases that have been treated by complete resection and/or radiotherapy demonstrating stability or improvement are not an exclusion criterion provided they are stable as shown by computed tomography (CT) scan for at least 4 weeks before Screening without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants.
  • 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.
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  • 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.

Trial locations and contacts

88 sites in 3 countries.

88 sites in 3 countries

China60 sites

  • Affiliated Hospital of Hebei University

    Baoding, Hebei

  • Beijing Friendship Hospital, Capital Medical University

    Beijing, Beijing Municipality

  • Beijing Cancer Hospital

    Beijing

  • Cancer Hospital, Chinese Academy of Medical Sciences

    Beijing

  • Chinese PLA General Hospital

    Beijing

  • Peking Union Medical College Hospital

    Beijing

  • Hebei Cangzhou Central Hospital

    Cangzhou, Hebei

  • Jilin Cancer Hospital

    Changchun, Jilin

  • Jilin Province People's Hospital

    Changchun, Jilin

  • The First Hospital of Jilin University

    Changchun, Jilin

  • The 2nd Xiangya Hospital of Central South University

    Changsha, Hu'nan

  • The Third Xiangya Hospital of Central South University

    Changsha, Hunan

  • West China Hospital, Sichuan University

    Chengdu, Sichuan

  • Chongqing University Cancer Hospital

    Chongqing, Chongqing Municipality

  • The Second Hospital of Dalian Medical University

    Dalian, Liaoning

  • Fujian Cancer Hospital

    Fuzhou, Fujian

  • Fujian Medical University Union Hospital

    Fuzhou, Fujian

  • Affiliated Cancer Hospital and Institute of Guangzhou Medical University

    Guangzhou, Guangdong

  • First Affiliated Hospital of Guangzhou University of TMC

    Guangzhou, Guangdong

  • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

    Guangzhou, Guangdong

  • Sun Yat-sen University, Cancer Center

    Guanzhou, Guangdong

  • Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine

    Hangzhou, Zhejiang

  • The First Affiliated Hospital, College of Medicine, Zhejiang University

    Hangzhou, Zhejiang

  • The Second Affiliated Hospital of Zhejiang University School of Medicine

    Hangzhou, Zhejiang

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang

  • Harbin Medical University Cancer Hospital

    Harbin, Heilongjiang

  • The First Affiliated Hospital of Anhui Medical University

    Hefei, Anhui

  • The Second Hospital of Anhui Medical University

    Hefei, Anhui

  • Jinan Central Hospital

    Jinan, Shangdong

  • Affiliated Hospital of Jining Medical University

    Jining, Shandong

  • Yunnan Cancer Hospital

    Kunming, Yunnan

  • Liuzhou General Hospital

    Liuzhou, Guangxi

  • The Second Affiliated Hospital of Nanchang University

    Nanchang, Jiangxi

  • Nanchong Central Hospital

    Nanchong, Sichuan

  • Jiangsu Cancer Hospital

    Nanjing, Jiangsu

  • Jiangsu Province Hospital

    Nanjing, Jiangsu

  • Nanjing Bayi Hospital

    Nanjing, Jiangsu

  • The Affiliated Drum Tower Hospital of Nanjing University

    Nanjing, Jiangsu

  • Nantong Tumor Hospital

    Nantong, Jiangsu

  • Fudan University Shanghai Cancer Center

    Shanghai, Shanghai Municipality

  • Ruijin Hospital of Shanghai Jiaotong University School of Medicine

    Shanghai, Shanghai Municipality

  • General Hospital of the Northern Theater of the Chinese People's Liberation Army

    Shenyang, Liaoning

  • Liaoning Cancer Hospital & Institute

    Shenyang, Liaoning

  • The First Hospital of China Medical University

    Shenyang, Liaoning

  • The University of Hong Kong-Shenzhen Hospital

    Shenzhen, Guangdong

  • The Fourth Hospital of Hebei Medical University

    Shijiazhuang, Hebei

  • Tianjin Medical University Cancer Institute & Hospital

    Tianjing, Tianjing

  • Hubei Cancer Hospital

    Wuhan, Hubei

  • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

    Wuhan, Hubei

  • Wuxi 4th People's Hospital

    Wuxi, Jiangsu

  • Shannxi Provincial Tumor Hospital

    Xi'an, Shangxi

  • The 2nd Hospital of Xi'An Jiaotong University

    Xi’an, Shanxi

  • The First Affiliated Hospital of Xi'an Jiaotong University

    Xi’an, Shanxi

  • The First Affiliated Hospital of Xiamen University

    Xiamen, Fujian

  • Affiliated Hospital of Qinghai University

    Xining, Qinghai

  • Xuzhou Central Hospital

    Xuzhou, Jiangsu

  • Northern Jiangsu People's Hospital

    Yangzhou, Jiangsu

  • Yantai Yuhuangding Hospital

    Yantai, Shangdong

  • Affiliated Hospital of Guangdong Medical University

    Zhanjiang, Guangdong

  • Henan Cancer Hospital

    Zhengzhou, Henan

Other trials in China

Ukraine23 sites

  • CTPI Chernihiv Regional Oncological Dispensary

    Chernihiv, 14029

  • CI Chernivtsi RC Oncological Dispensary

    Chernivtsi, 58013

  • CNE"City Clin Hosp#4"of Dnipro City Council Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU

    Dnipro, Dnipropetrovsk Oblast, 49102

  • CI Carpathian Clinical Oncological Center

    Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018

  • Communal Non-profit Enterprise Regional Center of Oncology

    Kharkiv, 61070

  • CI of Kherson Reg Council Kherson Regional Oncologic Dispensary

    Kherson, 73000

  • Khmelnytskyi Regional Oncological Dispensary

    Khmelnytskyi, 29000

  • Treatment-Diagnostic Center of Private Enterprise of PPC Atsynus

    Kropyvnytskyi, 25006

  • CI Kryvyi Rih Oncological Dispensary of DRC

    Kryvyi Rih, Dnipropetrovsk Oblast, 50048

  • National Institute of Cancer

    Kyiv, 03022

  • CNE Kyiv City Clin Oncological Center of Ex Body of Kyiv CC(KCSA)

    Kyiv, 03115

  • Kyiv Сity Clinical Oncological Center

    Kyiv, 03115

  • Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council

    Lutsk, Warren, 43018

  • CI of LRC Lviv Oncological Regional Treatment and Diagnostic Center

    Lviv, 79031

  • CI Odesa Regional Clinical Hospital

    Odesa, 65025

  • Odesa Regional Oncologic Dispensary

    Odesa, 65055

  • Poltava Reg Cl Onc Dispensary of PRC Chemotherapy Dept HSEI of Ukr UMSA

    Poltava, 36011

  • RCI Sumy Regional Clinical Oncological Dispensary Dept of of Chemotherapy Sumy SU

    Sumy, 40022

  • CNE CCCH of Uzh CC Oncological Center, Ther Dept, SHEI UNU

    Uzhhorod, Outer Carpathian, 88000

  • Transcarpathian Regional Clinical Oncological Dispensary

    Uzhhorod, Outer Carpathian, 88014

  • Podilskyi Regional Oncological Center

    Vinnytsia, 21029

  • CI Zaporizhzhia RC Onc Dispensary of ZRC Dept of Breast Pathology SI Zaporizhzhia MA of PGE of MoHU

    Zaporizhzhya, 69040

  • CI Zaporizhzhia Regional Clinical Oncological Dispensary of ZRC

    Zaporizhzhya, 69040

Other trials in Ukraine

Philippines5 sites

  • Cebu Doctors University Hospital

    Cebu City, 6000

  • Metro Davao Medical and Research Center, Inc.

    Davao City, Davao Region, 8000

  • Manila Doctors Hospital

    Manila, National Capital Region, 1000

  • The Medical City

    Pasig, National Capital Region, 1605

  • Cardinal Santos Medical Center

    San Juan City, La Union, 1502

Other trials in Philippines

About this study

Official title: 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

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.

Read the detailed description

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, recurrent or previously untreated metastatic breast cancer. Eligible patients will be assessed centrally for HER2 status and the presence of at least one measurable target lesion before randomization. Patients will undergo a tumor assessment for evaluation of response according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) every 6 weeks up to 24 weeks (regardless of the number of cycles actually given); thereafter, assessments will be done every 9 weeks (after Cycles 11, 14, and 17) or earlier in the case of clinical signs of progression.

Conditions
Breast Cancer
Being tested
HLX02, Herceptin®, docetaxel
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HLX02Biological

    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.

  • Herceptin®Biological

    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

  • docetaxelDrug

    75 mg/m2 will be administered on Day 2, Cycle 1.then be given every 3 weeks on Day 1 of each subsequent cycle

Study groups in NCT03084237
Study groupRoleWhat they receive
HLX02+DocetaxelExperimentalHLX02+Docetaxel
Receives: Biological: HLX02; Drug: docetaxel
Herceptin®+DocetaxelActive comparatorHerceptin®+Docetaxel
Receives: Biological: Herceptin®; Drug: docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From time of First treatment to week 24

Secondary outcomes (5)

  1. DoR

    The time from first documentation of CR or PR to the first documentation of progression.

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)，At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or Unequivocal progression of existing non-target lesions (Note: the appearance of one or more new lesions is also considered progression).

    Measured: Up to 2 years

  2. DCR

    The percentage of patients who achieve CR, PR, or stable disease (SD) of at least 12 weeks

    Measured: Up to 2 years

  3. CBR

    The proportion of patients who achieve CR, PR, or durable SD (SD ≥24 weeks)

    Measured: Up to 2 years

  4. Median PFS up to 12 Months

    Median Progression Survival time assessed at 12 months.The probability of being alive without documented progression up to 12 months after randomization.

    Measured: From time of first treatment to 12 months

  5. Overall Survival at 12, 24, and 36 Months

    the probability of being alive 12, 24, and 36 months after randomization

    Measured: From time of first treatment to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2017
  2. Study startNov 2016
  3. Primary completion23 Nov 2018
  4. Study completion28 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
652 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03084237
Sponsor's protocol ID
HLX02-BC01
Other IDs
2016-000206-10, 2016
Status last verified
Apr 2024
First submitted
14 Mar 2017
Last updated
17 May 2024
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 39954568

  • 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, 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.

    PubMed 33826080

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing HLX02, Herceptin® and docetaxel in people with Breast Cancer, run by Shanghai Henlius Biotech at 88 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 88 sites in China, Ukraine, Philippines. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ORR 24 (time frame: From time of First treatment to week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03084237, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2024.

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