The Efficacy and Safety of BAT8001 Injection for the Treatment of HER2-positive Advanced Breast Cancer

HER2-positive Advanced Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04185649
• Other study ID #: BAT-8001-002-CR
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 1, 2018
• Est. completion date: December 31, 2021

Study information

• Verified date: December 2019
• Source: Bio-Thera Solutions
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 410
• Est. completion date: December 31, 2021
• Est. primary completion date: July 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-positive Advanced Breast Cancer

Intervention

Biological:
• BAT8001 for injection
3.6 mg/kg, q3w, administered intravenously on day 1 of each treatment cycle, 21 days/treatment cycle.

Drug:
• Lapatinib
Lapatinib 1250 mg was administered orally once per day of each 21-day cycle.
• Capecitabine
Capecitabine 1000 milligrams per square meter (mg/m^2) was administered orally twice daily on Days 1-14 of each 21-day cycle.

Locations

Country	Name	City	State
China	Beijing Hospital	Beijing	Beijing
China	Beijing Shijitan Hospital	Beijing	Beijing
China	Peking union medical college hospital	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Jilin Cancer Hospital	Chang chun	Jilin
China	The First Bethune Hospital of Jilin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Foshan City No. 1 People's Hospital	Foshan	Guangdong
China	Cancer Center of Guangzhou Medical University	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Hospital. SYSU	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital of Hainan Medical College	Haikou	Hainan
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	Shandong Cancer Hospital	Jinan	Shandong
China	Jinzhou Central Hospital	Jinzhou	Liaoning
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	Linyi Cancer Hospital	Linyi	Shandong
China	Liuzhou workers hospital	Liuzhou	Guangxi
China	The First Affiliated Hospital of Henan University of science and technology	Luoyang	Henan
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	The Third Hospital of Nanchang	Nanchang	Jiangxi
China	Jiangsu Cancer Hospital	Nanning	Jiangsu
China	Chinese PLA General Hospital	Peking	Beijing
China	Fudan University Shanghai Cancer Hospital	Shanghai	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai
China	Shanghai Sixth People's Hospital	Shanghai	Shanghai
China	The Second Hospital of Anhui Medical University	Shanghai	Shanghai
China	Liaoning Cancer Hospital	Shenyang	Liaoning
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	Taizhou Hispotal of Zhejiang Province	Taizhou	Zhejiang
China	Weifang People's Hospital	Weifang	Shandong
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Tongji Hospital of Tongji Medical College of HUST	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	Affiliated Hospital of Jiangnan University	Wuxi	Jiangsu
China	Shanxi Cancer Hospital	Xi'an	Shanxi
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	The First Affiliated Hospital of Xixiang Medical College	Xinxiang	Henan
China	Yancheng City No. 1 People's Hospital	Yancheng	Jiangsu
China	Yichang Central Hospital	Yichang	Hubei
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	The First Affiliated Hospital of Guangdong Medical University	Zhanjiang	Guangdong
China	The Fifth Affiliated Hospital Sun Yat-sen University	Zhuhai	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Bio-Thera Solutions

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version (v1.1), or death from any cause during the study, whichever occurs first.	Up to approximately 18 months
Secondary	Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death from any cause.	Up to approximately 30 months
Secondary	Objective Response Rate (ORR)	ORR is defined as percentage of participants with partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of RECIST v1.1.	Up to approximately 30 months
Secondary	Duration of Response (DOR)	DOR is defined as as the time from the date of initial confirmed PR or CR to the date of disease progression or death within the study.	Up to approximately 30 months
Secondary	Clinical Benefit Rate (CBR)	CBR is defined as the proportion of subjects with best overall response (confirmed PR or CR) or with stable disease (confirmed SD) for at least 6 months;	Up to approximately 30 months
Secondary	Serum Concentration of BAT8001	Concentration of BAT8001 will be measured in serum from participants, who received BAT8001.	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)
Secondary	Serum Concentration of total antibody of BAT8001 for injection	Concentration of total antibody will be measured in serum from participants, who received BAT8001.	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)
Secondary	Plasma Concentration of batansine (a maytansine derivative, which is the 3AA-MDC complex)	Concentration of batansine will be measured in plasma from participants, who received BAT8001.	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)
Secondary	Percentage of Participants with Anti-therapeutic Antibodies (ATA) to BAT8001	ATA to BAT8001 were measured in serum of participants, who received BAT8001.	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)