Overview
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.
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.
Eligibility
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;