Clinical trial NCT05346224: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Breast Neoplasms
HER2-positive Breast Cancer
Keywords: Perjeta
Pertuzumab
early-stage
locally Advanced
neoadjuvant
adjuvant
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
First posted: 2022-04-26
Enrollment: 900
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel-Controlled
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: The total pathological complete response (tpCR) rate assessed by the Independent Review Committee (IRC)
timeFrame: immediately after the surgery
Secondary outcomes:
measure: Breast pathologic complete response (bpCR) rate
timeFrame: immediately after the surgery
Other outcomes:
Locations:
city: Bengbu
country: China
facility: the First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The first affiliated hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The first affiliated hospital of USTC (Anhui Provincial Hospital)
state: Anhui
city: Luan
country: China
facility: Lu'an people's hospital of Anhui ProvinceLuan
state: Anhui
city: Ma'anshan
country: China
facility: Maanshan People's Hospital
state: Anhui
city: Wuhu
country: China
facility: Yijishan Hospital of Wannan Medical College
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Chongqi
country: China
facility: he First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Affiliated Cancer Hospital and Institute of Guangzhou Medical University
state: Guangdong
city: Guanzhou
country: China
facility: Sun Yat-Sun Yat-sen Hospital affiliated to Sun Yat-sen Universitysen Hospital affiliated to Sun Yat-sen University
state: Guangdong
city: Jieyang
country: China
facility: Jieyang People's Hospital
state: Guangdong
city: Meizhou
country: China
facility: Meizhou People's Hospital
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
city: Shantou
country: China
facility: Shantou Central Hospital
state: Guangdong
city: Shaoguan
country: China
facility: Yue Bei People's Hospital
state: Guangdong
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan People's Hospital
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital
state: Guangxi Zhuang Autonomous Region
city: Guiyang
country: China
facility: Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Guiyang
country: China
facility: Affiliated Tumor Hospital of Guizhou Medical University
state: Guzhou
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Tangshan
country: China
facility: Tangshan People's Hospital
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Anyang
country: China
facility: Anyang Cancer Hospital
state: Henan
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of science and Technology
state: Henan
city: Nanyang
country: China
facility: Nanyang Central Hospital
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital of the Xinxiang Medical University
state: Henan
city: Xinxiang
country: China
facility: Xinxiang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: The Third Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College,Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Of Central South University
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital Of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The First Affiliated Hospital With Nanjing Medical University
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Wuxi
country: China
facility: affiliated Hospital of Jiangnan University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Nanchang Third Hospital
state: Jiangxi
city: Chang chun
country: China
facility: The first hospital of Jilin University
state: JIilin
city: Dalian
country: China
facility: The second hospital of dalian medical university
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shangdong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shangdong
city: Qingdao
country: China
facility: he Affiliated Hospital of Qingdao University
state: Shangdong
city: Qingdao
country: China
facility: Qingdao Central Hospital
state: Shangdong
city: Weifang
country: China
facility: Weifang People's Hospital
state: Shangdong
city: Weifang
country: China
facility: Weifang Hospital of traditional Chinese Medicine
state: Shangdong
city: Weihai
country: China
facility: Weihai Municipal Hospital
state: Shangdong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shangdong
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital
state: Shanxi
city: Xi'an
country: China
facility: Shaanxi Provincial People's Hospital
state: Shanxi
city: Xian
country: China
facility: The First Affiliated Hospital of Xi'an JiaoTong University
state: Shanxi
city: Yuncheng
country: China
facility: Yuncheng Central Hospital
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuang
city: Deyang
country: China
facility: People's hospital of Deyang city
state: Sichuang
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuang
city: Neijiang
country: China
facility: The second people's hospital of neijiang
state: Sichuang
city: Yibin
country: China
facility: The second people's hospital of Yibin
state: Sichuang
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Kunming
country: China
facility: The First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital Zhejiang University School Of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School Of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Pécs
country: Hungary
facility: University of Pécs, Department of Oncotherapy
state: Baranya
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
state: Łódź Voivodeship
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela (CHUS)
state: A Coruna
city: Barcelona
country: Spain
facility: Hospital Arnau de Vilanova de Lleida
state: Catalonia
Study officials:
References:
citation: 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) Administered to Healthy Male Subjects. BioDrugs. 2022 May;36(3):393-409. doi: 10.1007/s40259-022-00534-w. Epub 2022 May 20.