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

NCT ID: NCT03084237

Last Updated: 2024-05-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 652 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2021-09-28

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

HLX02+Docetaxel

HLX02+Docetaxel

Group Type: EXPERIMENTAL

HLX02

Intervention Type: 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.

docetaxel

Intervention Type: DRUG

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

Herceptin®+Docetaxel

Herceptin®+Docetaxel

Group Type: ACTIVE_COMPARATOR

Herceptin®

Intervention Type: 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

docetaxel

Intervention Type: DRUG

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

Interventions

HLX02

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.

Intervention Type: BIOLOGICAL

Herceptin®

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

Intervention Type: BIOLOGICAL

docetaxel

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Henlius Biotech

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Liuzhou, 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, Philippines

Cardinal Santos Medical Center

San Juan City, La Union, Philippines

Manila Doctors Hospital

Manila, National Capital Region, Philippines

The Medical City

Pasig, National Capital Region, Philippines

Cebu Doctors University Hospital

Cebu City, , Philippines

CI Kryvyi Rih Oncological Dispensary of DRC

Kryvyi Rih, Dnepropetrovsk, Ukraine

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

Dnipro, Dnipropetrovsk Oblast, Ukraine

CI Carpathian Clinical Oncological Center

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

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

Uzhhorod, Outer Carpathian, Ukraine

Transcarpathian Regional Clinical Oncological Dispensary

Uzhhorod, Outer Carpathian, Ukraine

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

Lutsk, Warren, Ukraine

CTPI Chernihiv Regional Oncological Dispensary

Chernihiv, , Ukraine

CI Chernivtsi RC Oncological Dispensary

Chernivtsi, , Ukraine

Communal Non-profit Enterprise Regional Center of Oncology

Kharkiv, , Ukraine

CI of Kherson Reg Council Kherson Regional Oncologic Dispensary

Kherson, , Ukraine

Khmelnytskyi Regional Oncological Dispensary

Khmelnytskyi, , Ukraine

Treatment-Diagnostic Center of Private Enterprise of PPC Atsynus

Kropyvnytskyi, , Ukraine

National Institute of Cancer

Kyiv, , Ukraine

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

Kyiv, , Ukraine

Kyiv Сity Clinical Oncological Center

Kyiv, , Ukraine

CI of LRC Lviv Oncological Regional Treatment and Diagnostic Center

Lviv, , Ukraine

CI Odesa Regional Clinical Hospital

Odesa, , Ukraine

Odesa Regional Oncologic Dispensary

Odesa, , Ukraine

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

Poltava, , Ukraine

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

Sumy, , Ukraine

Podilskyi Regional Oncological Center

Vinnytsia, , Ukraine

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

Zaporizhzhia, , Ukraine

CI Zaporizhzhia Regional Clinical Oncological Dispensary of ZRC

Zaporizhzhia, , Ukraine

Countries

China; Philippines; Ukraine

References

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.

Reference Type: DERIVED

PMID: 39954568 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33826080 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2016-000206-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HLX02-BC01

Identifier Type: -

Identifier Source: org_study_id