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

Breast Cancer Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Parallel-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of Pertuzumab Biosimilar HLX11 vs. EU-Perjeta® in the Neoadjuvant Therapy of HER2-Positive and HR-Negative Early-stage or Locally Advanced Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05346224
• Other study ID #: HLX11-BC301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 25, 2022
• Est. completion date: December 30, 2025

Study information

• Verified date: April 2023
• Source: Shanghai Henlius Biotech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 900
• Est. completion date: December 30, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Primary breast cancer that is:

1. Histologically confirmed invasive breast carcinoma with a primary tumor size of > 2 cm by standard local assessment technique;

2. 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);

3. HER2 positive confirmed by central laboratory, defined as immunohistochemistry (IHC) 3 +, or IHC 2+ and In Situ Hybridization (ISH) positive;

4. 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.

2. Left ventricular ejection fraction (LVEF) at baseline (within 42 days prior to randomization) = 55% measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan.

3. 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.

4. 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.

Exclusion Criteria:

1. Inflammatory breast cancer.

2. Stage IV (metastatic) breast cancer, bilateral breast cancer, or multicentric (multiple tumors involving more than 1 quadrant) breast cancer.

3. 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 ).

4. With serious heart disease or medical history, including but not limited to the following conditions:

1) 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).

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• HER2-positive Breast Cancer

Intervention

Drug:
• HLX11
Neoadjuvant(q3w/cycle,total 4cycle): HLX11(loading dose of 840 mg IV , followed by 420 mg IV q3w)+trastuzumab(loading dose of 8 mg/kg IV, followed by 6mg/kg IV q3w)+docetaxel(75mg/m2 IV q3w) Adjuvant: doxorubicin( 60 mg/m2 IV q3w)+cyclophosphamide( 600 mg/m2 IV q3w),total 4 cycle; trastuzumab(loading dose of 8mg/m2 IV , followed by 6 mg/m2 IV q3w)+HLX11(loading dose of 840 mg IV , followed by 420 mg IV q3w), 13cycle
• EU-Perjeta®
Neoadjuvant(q3w/cycle,total 4cycle): Perjeta (loading dose of 840 mg IV , followed by 420 mg IV q3w)+trastuzumab(loading dose of 8 mg/kg IV, followed by 6mg/kg IV q3w)+docetaxel(75mg/m2 IV q3w) Adjuvant: doxorubicin( 60 mg/m2 IV q3w)+cyclophosphamide( 600 mg/m2 IV q3w),total 4 cycle; trastuzumab(loading dose of 8mg/m2 IV , followed by 6 mg/m2 IV q3w)+HLX11 or Perjeta (loading dose of 840 mg IV , followed by 420 mg IV q3w), 13cycle

Locations

Country	Name	City	State
China	Sun Yat-Sun Yat-sen Hospital affiliated to Sun Yat-sen Universitysen Hospital affiliated to Sun Yat-sen University	Guanzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Henlius Biotech

Country where clinical trial is conducted

China, 

References & Publications (1)

Yang J, Lin L, Long Q, Zhang Q, Sun G, Zhou L, Wang Q, Zhu J, Li F, Hu W. HLX11, a Proposed Pertuzumab Biosimilar: Pharmacokinetics, Immunogenicity, and Safety Profiles Compared to Three Reference Biologic Products (US-, EU-, and CN-Approved Pertuzumab) A — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The total pathological complete response (tpCR) rate assessed by the Independent Review Committee (IRC)	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)	immediately after the surgery
Secondary	Breast pathologic complete response (bpCR) rate	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)	immediately after the surgery

External Links

•   Results from this study demonstrated the bioequivalence between HLX11 and US-, EU-, and CN-pertuzumab, supporting further investigation of HLX11 in clinical studies