Study of SHR-A2102 Combined Other Antitumor Drugs in Advanced Breast Cancer

Prior treatment

• Other malignancy within prior 2 years with no necessary treatment (except hormone replacement treatment) for at least recent 2 years, except: curatively treated in situ cancer of the cervix, skin basal cell carcinoma, skin squamous cell carcinoma or papillary thyroid carcinoma;
• Has received antitumor surgery, radiotherapy, chemotherapy, targeted therapy or immunological therapy within 4 weeks before first dose of study therapy; has received antitumor endocrine therapy within one week before first dose of study therapy;
• Adverse events caused by prior antitumor therapy have not recovered to ≤grade 1 per NCI-CTCAE v5.0 (except alopecia and tolerable, chronic grade 2 toxicity determined by investigator);
• Has received CYP3A4, CYP2D6, P-gp or BCRP potent inhibitors or inducers \<5-fold half-life of the drug before the first dose;
• Existence of arterial/venous thrombotic event within 6 months before first dose, such as cerebrovascular accidents (including transient ischemic attack, cerebral haemorrhage and cerebral infarction), deep venous thrombosis and pulmonary embolism;
• (Arm 2 only) Has received or been receiving PD-1/PD-L1 inhibitor;
• (Arm 2 only) Has active autoimmune disease or a history of autoimmune disease (including but not limited to: autoimmune hepatitis, uveitis, inflammatory bowel disease, hypophysitis, vasculitis, nephritis, hyperthyroidism, uncontrolled hypothyroidism only treated with hormone replacement therapy); subject that has skin disease unnecessary for systemic treatment (such as vitiligo, psoriasis, alopecia), controlled type I diabetes treated with insulin, or complete remission of asthma in childhood and no need to any intervention in adulthood can be enrolled; subject that has asthma which needs medical intervention by bronchodilators can not be enrolled; subject that has been receiving chronic, systemic steroid therapy (daily dose \>10mg prednisone or equivalent) or any other type of immunosuppressants within 2 weeks before the first dose of study therapy;
• (Arm 2 only) Has received a live vaccine within 4 weeks before first dose of study therapy, or potential to receive a live vaccine during the trial treatment;

Other illness

• Active brain metastasis; Stable brain metastasis (at least 4 weeks after intracranial local treatment, subjects should meet one of the following requirements: a. no signs of disease progression confirmed by imaging; b. no clinical symptom, and not necessary to corticosteroid or anticonvulsant therapy; c. with clinical symptom, but not necessary to increase dose of corticosteroid or combine with dexamethasone to control clinical symptom compared with intracranial local treatment) is allowed to be enrolled;
• Hypersensitivity to study therapy or any of its excipients;
• Has known clinically significant lung disease, including but not limited to: interstitial lung disease, pneumonitis, pulmonary fibrosis;
• Known history of immunodeficiency, including HIV-positive, other acquired or innate immunodeficient disease, or known history of organ transplantation, or known history of allogenic haemopoietic stem cell transplantation;
• Has an active infection requiring antibiotics, antiviral or antifungal treatment, or pyrexia \>38.5℃ of unknown origin during the screening period before first dose of study therapy (patients with pyrexia due to cancer could be enrolled determined by investigator);
• Other conditions that might influence the study and analysis of results in the opinion of the investigator.

Lab values

• Has active hepatitis B (HBsAg-positive and HBV DNA≥500 IU/mL), hepatitis C (positive for HCV antibody and HCV RNA above ULN) and hepatic cirrhosis;
• Known severe cardiac-cerebral vascular disease, including but not limited to: a) known severe cardiac rhythm or conduction disorder, such as ventricular arrhythmias necessary for clinical intervention, second or third degree atrioventricular block; b) under the resting state, QTcF\>470ms for female or 450ms for male examined by 12-lead ECG; c) acute coronary syndrome, congestive heart failure (NYHA classification of heart failure ≥ Class II), myocardial infarction, aortic dissection, cerebral stroke, or other ≥grade 3 cardiac-cerebral vascular events; d) LVEF\<50%; e) clinically uncontrolled hypertension;

Other

• Existence of third space fluid (e.g. massive ascites, pleural effusion, pericardial effusion which needs drainage again to relieve symptoms within 4 weeks after the first drainage) which is not well controlled by effective methods, e.g. drainage;
• Use of other antitumor systemic treatment during the study;

• 18 years to 75 years old (including boundary values), patients with advanced or metastatic breast cancer;
• ECOG PS Score: 0\~1;
• Based on RECIST v1.1, at least one measurable lesion;
• Patients must have a life expectancy ≥ 3 months;
• Adequate organ function and marrow function (no corrective treatment within 14 days before first dose);
• Women of childbearing potential (WOCBP) should agree to use an effective method of contraception and no lactation from the initiation of screening to 7 months after the last dose of study therapy; WOCBP should have a negative serum pregnancy result within 7 days before the first dose of study therapy; if unneutered male subjects (including using other sterilization except bilateral orchidectomy \[e.g. vasectomy\]) are willing to have sexual behaviour with WOCBP, one kind of contraception must be used to prevent the pregnancy of his partner from the date of enrolment to 7 months after the last dose of study therapy);
• Willing and able to provide written informed consent and comply with the requirements and restrictions in the protocol.