Clinical trial NCT04185649: The Efficacy and Safety of BAT8001 Injection for the Treatment of HER2-positive Advanced Breast Cancer
Official title: A Clinical Study Evaluating the Efficacy and Safety of BAT8001 Injection for the Treatment of HER2-positive Advanced Breast Cancer - A Multicenter, Randomized, Open-label, Positive-controlled, Superiority Phase III Clinical Trial in China
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: HER2-positive Advanced Breast Cancer
Lead sponsor: Bio-Thera Solutions
Sponsor class: INDUSTRY
First posted: 2019-12-04
Enrollment: 410
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of BAT8001 for the treatment of HER2-positive advanced breast cancer, using lapatinib in combination with capecitabine as the positive control drug.

Detailed description: This is a multicenter, randomized, open-label, positive-controlled, superiority phase III clinical study. The object is to evaluate the safety and efficacy of BAT8001 for the treatment of HER2-positive advanced breast cancer, using lapatinib in combination with capecitabine as the positive control drug.

Eligible subjects will be randomized to the experimental or control group in a 1:1 ratio and stratified by the number of HER2-positive advanced/metastatic breast cancer treatment regimens (0, 1 VS \> 1) and lesion site (organ VS non-organ).

Eligibility criteria: Inclusion Criteria:

1. Patients are required to provide at least 10 unstained sections.
2. HER2-positive (defined as: IHC 3+ or FISH+) confirmed by the central laboratory of this study.
3. Histologically and/or cytologically confirmed invasive breast cancer, including unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (MBC).
4. LABC or MBC that has progressed during or after treatment, or during or within 12 month following adjuvant therapy as confirmed by imaging.
5. Previously received adjuvant therapy, or locally advanced/metastatic breast cancer treatment regimen that included taxanes and trastuzumab (including approved biosimilars) as monotherapy or combination therapy。
6. At least one measurable lesion or a single metastatic tumor in the bone as per the Response Evaluation Criteria in Solid Tumor (RECIST) 1.1.
7. A score of 0-1 for performance status as per the Eastern Cooperative Oncology Group (ECOG) scale.
8. Expected survival ≥ 3 months.
9. Left ventricular ejection fraction (LVEF) ≥ 50%.
10. If anthracyclines are used, the cumulative dose must meet the following criteria: the cumulative dose must not exceed the equivalent dose of doxorubicin 500 mg/m2.
11. Women of childbearing age or fertile male subjects must agree to use oral, implanted, or injectable hormone contraceptives as well as one or two forms of non-hormonal contraceptive measures during the study period and until 6 months after the end of the study.
12. Blood pregnancy test must indicate non-pregnant for all women of childbearing potential and those who do not meet the definition of postmenopause.

Exclusion Criteria:

1. Current presence of grade ≥ 2 peripheral neuropathy.
2. History of other malignant tumors within the past 5 years, but does not include properly treated cervical carcinoma in situ, non-melanoma skin cancer, stage 1 uterine cancer, or other tumors with good prognosis.
3. Received treatment with a cancer drug or investigational drug within 21 days from the first dose of the study drug, except for hormone therapy..
4. Received radiation therapy within 14 days prior to the first test drug administration of this study; or subject has not recovered from the acute toxicity of radiation therapy prior to the first test drug administration of this study.
5. Brain metastasis that is symptomatic or requires treatment to control symptoms within 30 days before randomization.
6. Subjects who must receive the first test drug administration within less than 14 days following the completion of radiation therapy for symptomatic brain metastasis.
7. Currently experiences moderate or severe dyspnea at rest caused by advanced malignancy or other complications or severe primary lung diseases, or currently requires continuous oxygen therapy, or subject currently suffers from interstitial lung disease (ILD) or pneumonia/pneumonitis.
8. History of myocardial infarction or unstable angina within 6 months prior to first test drug administration.
9. Previous history of LVEF falling below 40%; or presence of symptomatic congestive heart failure (CHF) during trastuzumab (including other analogues) treatment.
10. Symptomatic congestive heart failure (CHF; New York Heart Association \[NYHA\] Class II-IV); Severe arrhythmias requiring treatment.
11. Presence of severe and uncontrollable systemic diseases (e.g. clinically significant cardiovascular, lung or metabolic diseases).
12. Patients who currently require coumarin derivative-based anticoagulation therapy such as warfarin and phenprocoumon.
13. Presence of diseases that may affect intestinal absorption, including malabsorption syndrome, stomach and small bowel resection, and ulcerative colitis.
14. Intolerance (grade 3-4 infusion reactions) or allergy to trastuzumab (and other analogues) or mouse proteins or any ingredient of the medication.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 18 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 30 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 30 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 30 months
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 30 months
measure: Serum Concentration of BAT8001
timeFrame: Pre-dose and 15-30 minutes after dose on Day 1, Day 8, Day 15 of each 21-day cycle during Cycles 1-4 and at completion/early termination visit (up to approximately 30 months)
measure: Serum Concentration of total antibody of BAT8001 for injection
timeFrame: Pre-dose and 15-30 minutes after dose on Day 1, Day 8, Day 15 of each 21-day cycle during Cycles 1-4 and at completion/early termination visit (up to approximately 30 months)
measure: Plasma Concentration of batansine (a maytansine derivative, which is the 3AA-MDC complex)
timeFrame: Pre-dose and 15-30 minutes after dose on Day 1, Day 8, Day 15 of each 21-day cycle during Cycles 1-4 and at completion/early termination visit (up to approximately 30 months)
measure: Percentage of Participants with Anti-therapeutic Antibodies (ATA) to BAT8001
timeFrame: Pre-dose on Day 1 of each 21-day cycle during Cycles 1-4 and at completion/early termination visit (up to approximately 30 months)
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Shijitan Hospital
state: Beijing
city: Beijing
country: China
facility: Peking union medical college hospital
state: Beijing
city: Peking
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Foshan
country: China
facility: Foshan City No. 1 People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital. SYSU
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Zhanjiang
country: China
facility: The First Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital Sun Yat-sen University
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou workers hospital
state: Guangxi
city: Haikou
country: China
facility: The First Affiliated Hospital of Hainan Medical College
state: Hainan
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of science and technology
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xixiang Medical College
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College of HUST
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Yichang
country: China
facility: Yichang Central Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Nanning
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
state: Jiangsu
city: Yancheng
country: China
facility: Yancheng City No. 1 People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The Third Hospital of Nanchang
state: Jiangxi
city: Chang chun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jilin
city: Jinzhou
country: China
facility: Jinzhou Central Hospital
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Weifang
country: China
facility: Weifang People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: The Second Hospital of Anhui Medical University
state: Shanghai
city: Xi'an
country: China
facility: Shanxi Cancer Hospital
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hispotal of Zhejiang Province
state: Zhejiang
Study officials:
affiliation: Sun Yat-sen University
name: Shusen Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: