a study of rc48-adc for the treatment of locally advanced or metastatic breast cancer with low expression of her2

Conditions: Breast Cancer

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.

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.

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;