A Study of RC48-ADC for the Treatment of Locally Advanced or Metastatic Breast Cancer With Low Expression of HER2

NCT ID: NCT04400695

Last Updated: 2024-01-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 366 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-29
• Study Completion Date: 2024-12-30

Brief Summary

This study will compare RC48-ADC to physician choice standard treatment. Participants must have HER2-low breast cancer ，previous use of anthracyclines, and have been treated with one or two systemic chemotherapy regimens following recurrence/metastasis.

Detailed Description

This study is a multi-center, randomized, open, parallel control to evaluate the effectiveness and safety of Phase III clinical trials of the efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody-Monomethyl auristatin E (MMAE) conjugate for the treatment of locally advanced or metastatic breast cancer the study.The low expression of HER2 is defined as: the immunohistochemistry (IHC) confirmed by the central laboratory detects the expression of HER2 protein as IHC 2+ and the fluorescence in situ hybridization (FISH) detection has no amplification.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RC48-ADC

RC48-ADC common name：Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection Dosage form：Lyophilized powder injection specification：60 mg / piece Medication plan：Every 2 weeks Expiration date：18 months HER2-low, unresectable, locally advanced or metastatic breast cancer participants previously treated with anthracycline and received 1 or 2 systemic chemotherapy after relapse / metastasis.

Group Type: EXPERIMENTAL

RC48-ADC

Intervention Type: DRUG

RC48-ADC 2.0mg / kg, intravenous drip, once every 2 weeks

Physician's Choice

Physician's Choice:

HER2-low, unresectable, locally advanced or metastatic breast cancer participants previously treated with anthracycline and received 1 or 2 systemic chemotherapy after relapse / metastasis.

Physician's choice from the following options:

Paclitaxel Injection Docetaxel Injection Vinorelbine Tartrate Injection Capecitabine Tablets

Group Type: ACTIVE_COMPARATOR

Paclitaxel Injection

Intervention Type: DRUG

Administered according to label, as one option for Physician's Choice (determined before randomization)

Docetaxel Injection

Intervention Type: DRUG

Administered according to label, as one option for Physician's Choice (determined before randomization)

Vinorelbine Tartrate Injection

Intervention Type: DRUG

Administered according to label, as one option for Physician's Choice (determined before randomization)

Capecitabine Tablets

Intervention Type: DRUG

Administered according to label, as one option for Physician's Choice (determined before randomization)

Interventions

RC48-ADC

RC48-ADC 2.0mg / kg, intravenous drip, once every 2 weeks

Intervention Type: DRUG

Paclitaxel Injection

Administered according to label, as one option for Physician's Choice (determined before randomization)

Intervention Type: DRUG

Docetaxel Injection

Administered according to label, as one option for Physician's Choice (determined before randomization)

Intervention Type: DRUG

Vinorelbine Tartrate Injection

Administered according to label, as one option for Physician's Choice (determined before randomization)

Intervention Type: DRUG

Capecitabine Tablets

Administered according to label, as one option for Physician's Choice (determined before randomization)

Intervention Type: DRUG

Other Intervention Names

RC48; Taxol; Taxotere; Navelbine; Xeloda

Eligibility Criteria

Inclusion Criteria

• Voluntarily agree to participate in the study and sign the informed consent;
• Subjects aged 18-70 years (including 18 years and 70 years) and not reaching the 71st birthday were all considered to be ≤70 years old;
• Expected survival ≥12 weeks;
• Eastern Cooperative Oncology Group(ECOG) physical condition 0 or 1;
• For female subjects of child-bearing age women agreed to study during treatment and experimental subjects within 6 months after the end of the treatment period using an approved by the medical contraception (e.g. intrauterine device, the pill or condoms), before the study drug delivery within 7 days of pregnancy blood test must be negative (sterilization surgery or age 60 or more subjects can choose no pregnancy blood test), and must be an lactation. For male subjects: should be sterilized surgically, or agree to use a medically approved contraceptive method during the study period and for 6 months after the end of the treatment period. Control subjects after the end of the treatment period according to the choice of control drugs to determine the length of contraception.
• Able to understand the study requirements and be willing and able to follow the study and follow-up procedures.
• Bone marrow function:

hemoglobin ≥9g/dL; absolute neutrophil count ≥1.5×109/L; white blood cell count ≥3.0×109/L platelet ≥100 ×109/L;

• Liver function (according to the normal value of the clinical trial center) :

serum total bilirubin ≤1.5 times the upper limit of normal value (ULN); alanine aminotransferase (ALT), aspartate aminotransferase(AST) and Alkaline phosphatase（ALP） were ≤2.5 × ULN in the absence of liver metastasis, and ALT, AST and Alkaline phosphatase(ALP) were ≤5 × ULN in the presence of liver metastasis

• Renal function (according to the normal value of the clinical trial center) :

serum creatinine ≤1.5×ULN, or calculated by Cockcroft-Gault formula, the creatinine clearance rate (CrCl) ≥60 mL/min;

• Cardiac function:

American New York college of cardiology (NYHA) grade < 3; left ventricular ejection fraction ≥50%;

• Breast cancer subjects diagnosed by histology and / or cytology are currently at a locally advanced or metastatic stage and cannot be radically removed;
• The low expression of HER2 confirmed by the IHC and FISH results of the central laboratory (defined as: IHC 2+ and no amplification of FISH); the subject can provide a specimen of the primary or metastatic tumor site (paraffin wax) for HER2 detection Block, paraffin-embedded section or fresh tissue section can be used);
• Previous use of anthracycline drugs;
• Received 1 or 2 systemic chemotherapy treatments after relapse / metastasis. Subjects who relapsed during adjuvant chemotherapy or within 12 months after the end of adjuvant chemotherapy were considered to have failed first-line chemotherapy after relapse / metastasis.
• Hormone receptors are negative or positive. Hormone receptor-positive subjects need to progress after receiving endocrine therapy after relapse / metastasis or relapse after less than 2 years. Patients who are not suitable for endocrine therapy can be included in this study after undergoing chemotherapy treatment (first-line or second-line);
• The imaging evidence confirmed by the investigator that the tumor disease progressed during or after the most recent treatment is required;
• There has been no diagnosis of HER2 positive (HER2 IHC 3+ or FISH amplification)
• Have not used drugs targeting HER2 (including antibodies, small molecule Tyrosine kinase inhibitor（TKIs） and antibody drug conjugates).
• According to the RECIST 1.1 standard, there is at least one measurable lesion.

Exclusion Criteria

• Received chemotherapy within 4 weeks before the start of study administration (treatment with nitrosourea and mitomycin C within 6 weeks, oral fluorouracil within 2 weeks), radiotherapy (palliative for bone metastases Local radiotherapy is within 2 weeks before study administration), immunotherapy; received endocrine therapy for breast cancer within 2 weeks before study administration;
• The research drug was used within 4 weeks before the start of study administration;
• Have undergone major surgery within 4 weeks before the start of study administration;
• Have received a live vaccine within 4 weeks before the start of study administration or plan to receive any vaccine during the study period;
• Serious cardiovascular and cerebrovascular events occurred within 12 months, including but not limited to unstable angina, myocardial infarction, cerebral hemorrhage, and cerebral infarction (except for asymptomatic and untreated lacunar infarction)；
• Those who are suffering from heart disease are not suitable for enrollment, including but not limited to arrhythmia and heart failure requiring medical treatment or accompanied by symptoms;
• There are other lung diseases requiring treatment or serious, including but not limited to active pulmonary tuberculosis, interstitial lung disease, etc ;
• Suffering from active infection requiring systemic treatment;
• Have active autoimmune diseases (such as the use of corticosteroids or immunosuppressive drugs, etc.) that require systemic treatment within the past 2 years, allowing related alternative treatments (such as thyroxine, insulin, or the physiology of adrenal or pituitary insufficiency Corticosteroid replacement therapy);
• The toxicity of the previous anti-tumor therapy has not been restored to the 0 to 1 level defined by CTCAE version 5.0, of which the neurotoxicity has not been restored to 0; except for hair loss, pigmentation or other researches that do not increase the risk of medication Happening;
• Have a clear past or current history of neurological or mental disorders, including epilepsy or dementia;
• According to the investigator's judgment, there are concomitant diseases that seriously endanger the safety of the subject or affect the completion of the clinical study；
• Positive HIV test results; patients with active hepatitis B or C (HBsAg positive and hepatitis B virus（HBV） DNA titers above the upper limit of normal; Hepatitis C Virus Antibody(HCVAb) positive hepatitis C virus （HCV） RNA titers above the upper limit of normal)；
• There is a third interstitial fluid that cannot be controlled by drainage or other methods (including a large amount of pleural effusion or ascites);
• Known hypersensitivity or delayed allergic reaction to certain components of RC48-ADC or similar drugs;
• Subjects who are not suitable for using any of the alternative control drugs;
• The presence of brain metastases and / or cancerous meningitis;
• Have other malignant tumors within 5 years before signing the informed consent form (except for non-melanoma skin cancer, cervical carcinoma in situ or other tumors that have been effectively treated, except malignant tumors that are considered cured);
• Subjects who are estimated to be inadequate for patients to participate in this clinical study or other factors that the investigator believes are inappropriate to participate in this study;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RemeGen Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Binghe Xu

Role: PRINCIPAL_INVESTIGATOR

Oncology Hospital, Chinese Academy of Medical Sciences

Tao Sun

Role: PRINCIPAL_INVESTIGATOR

Liaoning Cancer Hospital & Institute

Wei Li

Role: PRINCIPAL_INVESTIGATOR

Jilin University First Hospital

Yuee Teng

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital of China Medical University

Shu Wang

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Xiaojia Wang

Role: PRINCIPAL_INVESTIGATOR

Zhejiang Cancer Hospital

Min Yan

Role: PRINCIPAL_INVESTIGATOR

Henan Cancer Hospital

Jifeng Feng

Role: PRINCIPAL_INVESTIGATOR

Jiangsu Cancer Institute & Hospital

Ying Cheng

Role: PRINCIPAL_INVESTIGATOR

Jilin Provincial Tumor Hospital

Ying Wang

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Ying Wang

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University Cancer Prevention and Control Center

Ning Liao

Role: PRINCIPAL_INVESTIGATOR

Guangdong Provincial People's Hospital

Haibo Wang

Role: PRINCIPAL_INVESTIGATOR

Qingdao University Hospital

Quchang Ouyang

Role: PRINCIPAL_INVESTIGATOR

Hunan Cancer Hospital

Yueyin Pan

Role: PRINCIPAL_INVESTIGATOR

Anhui Provincial Hospital

Yingying Du

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Anhui Medical University

Changlu Hu

Role: PRINCIPAL_INVESTIGATOR

Anhui Provincial Cancer Hospital

Zhongsheng Tong

Role: PRINCIPAL_INVESTIGATOR

Tianjin Cancer Hospital

Jin Yang

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine

Lihua Song

Role: PRINCIPAL_INVESTIGATOR

Shandong Cancer Hospital and Institute

Xiuwen Wang

Role: PRINCIPAL_INVESTIGATOR

Qilu Hospital of Shandong University

Yu Jiang

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Yunjiang Liu

Role: PRINCIPAL_INVESTIGATOR

Hebei Medical University Fourth Hospital

Jing Cheng

Role: PRINCIPAL_INVESTIGATOR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Huihua Xiong

Role: PRINCIPAL_INVESTIGATOR

Tongji Hospital

Xinhong Wu

Role: PRINCIPAL_INVESTIGATOR

Hubei Cancer Hospital

Peng Shen

Role: PRINCIPAL_INVESTIGATOR

Zhejiang University

Weimin Xie

Role: PRINCIPAL_INVESTIGATOR

Cancer Hospital Affiliated to Guangxi Medical University

Xin Zhou

Role: PRINCIPAL_INVESTIGATOR

Chongqing University Cancer Hospital

Li Ran

Role: PRINCIPAL_INVESTIGATOR

Cancer Hospital of Guizhou Province

Yu Wang

Role: PRINCIPAL_INVESTIGATOR

Shanxi Province Cancer Hospital

Jinnan Gao

Role: PRINCIPAL_INVESTIGATOR

Bethune Hospital of Shanxi Province

Jingfen Wang

Role: PRINCIPAL_INVESTIGATOR

Linyi Cancer Hospital

Liangming Zhang

Role: PRINCIPAL_INVESTIGATOR

Yantai Yuhuangding Hospital

Xianhe Xie

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital of Fujian Medical University

Ru Zeng

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Xiamen University

Airong Wang

Role: PRINCIPAL_INVESTIGATOR

Weihai Municipal Hospital

Zhengqiu Zhu

Role: PRINCIPAL_INVESTIGATOR

The Affiliated Hospital of Xuzhou Medical University

Sanyuan Sun

Role: PRINCIPAL_INVESTIGATOR

Xuzhou Central Hospital

Qingshan Li

Role: PRINCIPAL_INVESTIGATOR

Affiliated Hospital of Chengde Medical College

Aimin Zang

Role: PRINCIPAL_INVESTIGATOR

Affiliated Hospital of Hebei University

Liuzhong Yang

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Xinxiang Medical College

Meili Sun

Role: PRINCIPAL_INVESTIGATOR

Jinan Central Hospital

Liang Li

Role: PRINCIPAL_INVESTIGATOR

Zibo Central Hospital

Guohua Yu

Role: PRINCIPAL_INVESTIGATOR

Weifang People's Hospital

Xujuan Wang

Role: PRINCIPAL_INVESTIGATOR

Neijiang Second People's Hospital

Locations

Oncology Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Binghe Xu, M.D.

Role: CONTACT

bhxu@hotmail.com

010-87788826

Facility Contacts

Binghe Xu

Role: primary

bhxu@hotmail.com

010-87788826

Other Identifiers

RC48-C012

Identifier Type: -

Identifier Source: org_study_id