A Phase II Study of T-DXd Plus SRT in HER2-positive Breast Cancer Brain Metastases

Inclusion criteria

• Pathologically confirmed HER2 positive advanced breast cancer
• Age>18 years.
• Brain metastases confirmed by enhanced brain MRI. Metastases number less than 15.
• KPS≥70 or KPS ≥60 with neurologic symptoms caused by BM
• Life expectancy of more than 6 months
• Prior therapy of oral dexamethasone not exceeding 16mg/d
• Time interval from prior therapy was more than 2 weeks, and evaluation of adverse events is no more than grade 1.
• Screening laboratory values must meet the following criteria( and should be obtained within 28 days prior to registration):

• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets≥ 90 x 109/L, Hemoglobin ≥ 90 g/L
• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 x ULN without liver metastasis,≤ 5 x ULN with liver metastases
• Serum BUN and creatinine ≤ 1.5 x Upper Limit of Normal (ULN)
• LVEF ≥ 50%
• QTcF < 480 ms
• INR≤1.5×ULN，APTT≤1.5×ULN
• Signed the informed consent form prior to patient entry

Exclusion criteria

• Leptomeningeal or hemorrhagic metastases
• Uncontrolled epilepsy
• Severe or uncontrolled disease: severe cardiovascular disease, end-stage renal disease, severe hepatic disease, history of immunodeficiency, including HIV positive, active HBV/HCV or other acquired congenital immunodeficiency disease, or organ transplantation history, active infection, etc.
• History of allergy to treatment regimens
• Pregnancy or lactation period， women of child-bearing age who are unwilling to accept contraceptive measures.
• Inability to complete enhanced MRI
• Not suitable for inclusion for specific reasons judged by sponsor