A Study to Evaluate the Efficacy and Safety of HLX11 Vs. EU-Perjeta® in the Neoadjuvant Therapy of HER2-Positive and HR-Negative Early-stage or Locally Advanced Breast Cancer
- Conditions
- Breast NeoplasmsHER2-positive Breast CancerBreast Cancer
- Interventions
- Drug: EU-Perjeta®
- Registration Number
- NCT05346224
- Lead Sponsor
- Shanghai Henlius Biotech
- Brief Summary
This is a phase III, double-blind, randomized, parallel-controlled, multicenter equivalence study to compare the efficacy and safety of pertuzumab biosimilar HLX11 vs. EU-Perjeta® on HER2-positive and HR-negative early-stage or locally advanced breast cancer with a primary tumor \> 2 cm.
Patients are random assignment to 2 arms and treatment with either HLX11 or EU-Perjeta® , and received neoadjuvant THP regimen every 3- weeks 4 cycles，adjuvant AC every 3- weeks 4 cycles and pertuzumab+trastuzumab(HP) every 3- weeks 13cycles.
- Detailed Description
This is a phase III, double-blind, randomized, parallel-controlled, multicenter equivalence study to compare the efficacy and safety of pertuzumab biosimilar HLX11 vs. EU-Perjeta® on HER2-positive and HR-negative early-stage or locally advanced breast cancer with a primary tumor \> 2 cm.Subjects will be randomly assigned to treatment group (HLX11) or control group (EU-Perjeta®) at 1:1 ratio. The stratification factors include disease category (early-stage vs. locally advanced) and geographic region (Asia vs. non-Asia).
Study drugs will be administered intravenously on a 3-weekly schedule and given consecutively on the same day in the following sequence trastuzumab, followed by pertuzumab and docetaxel(THP regimen) for neoadjuvant，Doxorubicin in combination with cyclophosphamide (AC) for adjuvant chemotherapy, then HP regimen for adjuvant HER2-targeted.
The primary endpoint is total pCR (tpCR) . Secondary efficacy endpoints include breast pCR (bpCR), objective response rate (ORR),Event-free survival (EFS) and Disease-free survival (DFS).
The safety indicators is incidence, type, severity, and causality of all adverse events (including serious adverse events and AESI) based on NCI CTCAE v5.0; Vital signs, physical examination, laboratory tests, cardiac function test, etc.
pharmacokinetic(PK) and immunogenicity is also assessed.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 900
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Primary breast cancer that is:
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Histologically confirmed invasive breast carcinoma with a primary tumor size of > 2 cm by standard local assessment technique;
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Breast cancer staging ( in accordance with the American Joint Commitee on Cancer(AJCC) staging system (8th edition)): early-stage (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0; T4, any N, M0);
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HER2 positive confirmed by central laboratory, defined as immunohistochemistry (IHC) 3 +, or IHC 2+ and In Situ Hybridization (ISH) positive;
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Hormone receptor (HR, including estrogen receptor [ER] and progestin receptor [PR]) negative by central laboratory; ER negative is defined as < 1% nuclear staining, and PR negative is defined as < 1% nuclear staining.
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Left ventricular ejection fraction (LVEF) at baseline (within 42 days prior to randomization) ≥ 55% measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan.
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Adequate major organ function, meeting the following criteria: Hematology (neither blood transfusion nor correction with hematopoietic stimulating factors within 14 days prior to randomization): white blood cell count ≥ 3.0 × 109/L; absolute neutrophil count ≥ 1.5 × 109/L; hemoglobin ≥ 90 g/L; platelet count ≥ 100 × 109/L; Serum chemistry: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN; for subjects with known Gilbert syndrome, total bilirubin ≤ 2 × ULN; alkaline phosphatase ≤ 2.5 × ULN, serum creatinine ≤ 1.5 × ULN.
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Women of child-bearing potential have a negative result of serum pregnancy test at screening (within 7 days prior to randomization) and not in lactation, or are infertile. Male participants and women of childbearing potential use a "highly effective" contraceptive measures until 7 months after the last dose of investigational/reference product.
- Inflammatory breast cancer.
- Stage IV (metastatic) breast cancer, bilateral breast cancer, or multicentric (multiple tumors involving more than 1 quadrant) breast cancer.
- History of other malignancy within 5 years prior to screening (except for who have received radical treatment of carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin ).
- With serious heart disease or medical history, including but not limited to the following conditions:
- History of documented heart failure or systolic dysfunction with any NYHA classification(LVEF < 50%); 2) High-risk uncontrolled arrhythmia, such as atrial tachycardia with a heart rate> 100 bpm at rest, significant ventricular arrhythmia (e.g.,ventricular tachycardia), or higher-grade atrioventricular (AV) block (i.e.,Mobitz II second-degree AV block or third degree AV block); 3) Unstable angina pectoris, or angina pectoris requiring anti-angina medication; 4) Evidence of transmural myocardial infarction on ECG; 5) Clinically-significant valvular heart disease; 6) Poorly controlled hypertension (systolic blood pressure> 150 mmHg and/or diastolic blood pressure> 100 mmHg).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control group EU-Perjeta® Perjeta combined with trastuzumab and docetaxel will be adopted in the neoadjuvant treatment phase, and doxorubicin with cyclophosphamide will be administered in the adjuvant chemotherapy treatment phase, HLX11 or Perjeta combined with trastuzumab will be administered in the adjuvant treatment phase for HER-2 targeted. Treatment group HLX11 HLX11 combined with trastuzumab and docetaxel will be adopted in the neoadjuvant treatment phase, and doxorubicin with cyclophosphamide will be administered in the adjuvant chemotherapy treatment phase, HLX11 combined with trastuzumab will be administered in the adjuvant treatment phase for HER-2 targeted.
- Primary Outcome Measures
Name Time Method The total pathological complete response (tpCR) rate assessed by the Independent Review Committee (IRC) immediately after the surgery tpCR is defined as the histological evidence of no malignancy of lymph nodes in the regions of primary lesion and metastasis of breast cancer (i.e., ypT0/is, ypN0 in accordance with the AJCC staging system)
- Secondary Outcome Measures
Name Time Method Breast pathologic complete response (bpCR) rate immediately after the surgery bpCR is defined as the histological evidence of no malignancy in the primary lesion of breast cancer, or only carcinoma in situ (i.e., ypT0/Tis in the AJCC staging system, 8th edition)
Trial Locations
- Locations (16)
the First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, Anhui, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
The first affiliated hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
The first affiliated hospital of USTC (Anhui Provincial Hospital)
🇨🇳Hefei, Anhui, China
Affiliated Cancer Hospital and Institute of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, Guangdong, China
Shantou Central Hospital
🇨🇳Shantou, Guangdong, China
Guangxi Medical University Affiliated Tumor Hospital
🇨🇳Nanning, Guangxi Zhuang Autonomous Region, China
Union Hospital, Tongji Medical College,Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Xiangya Hospital Of Central South University
🇨🇳Changsha, Hunan, China
The Second Xiangya Hospital Of Central South University
🇨🇳Changsha, Hunan, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital With Nanjing Medical University
🇨🇳Nanjing, Jiangsu, China
Xuzhou Central Hospital
🇨🇳Xuzhou, Jiangsu, China
Sun Yat-Sun Yat-sen Hospital affiliated to Sun Yat-sen Universitysen Hospital affiliated to Sun Yat-sen University
🇨🇳Guanzhou, Guangdong, China