ARX788 in HER2-positive Breast Cancer Patients With Brain Metastases

Inclusion Criteria:

• Age ≥18 years, and ≤75 years, male or female;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0~2;
• Breast cancer patients diagnosed as HR arbitrary/HER2-positive by pathologicalexamination;
• Metastatic breast cancer subjects previously treated with trastuzumab, taxane andEGFR-TKI-containing regimens;
• MRI confirmed brain metastasis with at least one intracranial parenchymal untreatedmetastatic lesion;
• Mannitol, bevacizumab, or hormone therapy is allowed before enrollment;
• Adequate organ functions;
• Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolvedto Grade ≤1.
• Patients who participate in the trial voluntarily, sign an informed consent, have goodcompliance and are willing to comply with the follow-up visit.

Exclusion Criteria:

• Pneumomeningeal metastases or cystic metastases confirmed by MRI or lumbar puncture;
• Uncontrolled third space effusion;
• Previous treatment with T-DM1 or other HER2-ADC drugs;
• Received a whole-brain radiotherapy, chemotherapy, or surgery within 2 weeks prior tothe first dose of ARX788, or trastuzumab-targeted therapy or endocrine therapy within 1 week, or palliative radiotherapy for bone metastases within 2 weeks;
• Prior history of interstitial pulmonary disease requiring hormone therapy,drug-induced interstitial pulmonary disease, radiation pneumonia, or currentclinically active interstitial pulmonary disease;
• Suffering from keratitis, corneal diseases, retinal diseases or active eye infectionsthat require intervention;
• Unwilling or unable to stop wearing contact lenses for the duration of the study;
• Participated in other clinical trials within 2 weeks prior to enrollment;
• Receiving any antitumor therapy for any other tumor, bevacizumab for the control ofbrain edema and bisphosphonates for the treatment of bone metastases or the preventionof osteoporosis are the exception;
• With a history of any malignancies other than breast cancer in the past 5 years,excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin orsquamous cell carcinoma of the skin;
• Cardiac insufficiency;
• Uncontrolled hypertension;
• History of allergic reactions to any component of ARX788, or with a history of proteindrug allergy, a history of specific allergies (asthma, rheumatism, eczematousdermatitis), or a history of other severe allergic reactions, who are unsuitable forARX788 treatment as per the investigator's judgments;
• Pregnancy or lactation;
• History of immunodeficiency, including HIV-positive, or other acquired or congenitalimmunodeficiency diseases, or a history of organ transplantation;
• Current known active infection with human immunodeficiency virus (HIV), hepatitis Bvirus, hepatitis C virus or syphilis;
• History of neurological or psychiatric disorder, including epilepsy or dementia;
• Suffering severe or uncontrolled systemic diseases.