SHR2554 Combined With Endocrine Therapy in Advanced Breast Cancer

Prior treatment

• Has received or been receiving ADC therapy;
• 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 2 weeks or 5-fold half-life of drugs (whichever is shorter) 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 median or potent inhibitors within 2 weeks before the first dose, or CYP3A4 median or potent inducers within 4 weeks before the first dose, or been receiving known CYP3A5 median or potent inhibitors or inducers;
• Known clinically severe cardiac-cerebral vascular disease, including: (1) congestive heart failure (NYHA Class \>2); (2) unstable angina pectoris; (3) myocardial infarction over the past year; (4) any supraventricular or ventricular arrhythmia needed to treat or intervene; ECG abnormality of clinical significance evaluated by investigators; existence of arterial/venous thrombotic event within 6 months before first dose, or cerebrovascular accidents, or transient ischemic attack;

Other illness

• Hypersensitivity to study therapy or any of its excipients;
• Uncontrolled chronic, systemic complicating disease evaluated by investigators (e.g. severe, chronic pulmonary, hepatic, renal or heart disease);
• 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);
• Inability to take oral medication (e.g., unable to swallow, intestinal obstruction), or any active gastrointestinal disease or other condition resulting in inability to drug absorption, distribution, metabolism or excretion (e.g., active gastroenteritis, chronic diarrhoea, intestinal syndrome, or upper gastrointestinal surgery, including gastrectomy);
• 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;

Other

• Active brain metastasis (without medical control or having clinical symptoms), carcinomatous meningitis or spinal compression;
• Existence of third space fluid (e.g. massive ascites, pleural effusion) which is not well controlled by effective methods, e.g. drainage, evaluated by investigators;
• Use of other antitumor systemic treatment during the study;

• ≥ 18 years old, 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.