A Phase II Study of SHR-A1811 Combined With Radiotherapy in HER2-positive and HER2-low Breast Cancer Brain Metastases

• SHR-A1811 and radiotherapy (Combination product): SHR-A1811:4.8mg/kg radiotherapy: 800cGY*5

Primary outcomes

• The objective response rate of intracranial（IC-ORR） [2 years]: Proportion of participants with a complete response (CR) or partial response (PR) for intracranial tumors

Secondary outcomes

• Intracranial CNS Progression Free Survival(IC-PFS) [2 years]: Time from treatment until the first date of intracranial disease progression or death due any cause. For participants whose disease has not progressed at the time of the analysis, censoring will be performed using the date of the last valid disease assessment.
• Progression Free Survival(PFS) [2 years]: Time from treatment until the first date of intracranial or extracranial disease progression or death due any cause. For participants whose disease has not progressed at the time of the analysis, censoring will be performed using the date of the last valid disease assessment.
• Overall survival(OS) [3 years]: Time from the treatment until to the date of death, regardless of the cause of death
• Adverse Events [2 years]: Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

1. Pathologically confirmed HER2 positive (IHC 3+ or IHC 2+/FISH+)or HER2-low(IHC1+ or 2+/FISH-) advanced breast cancer
2. Age>18 years.
3. newly diagnosed Brain metastases confirmed by enhanced brain MRI. Metastases number less than 6.
4. No more than four lines of previous advanced therapy
5. Life expectancy of more than 3 months
6. There were no known or suspected leptomeningeal brain metastases
7. The interval from previous therapy was more than 2 weeks, and acute toxicity from previous therapy had to resolve to grade 1 or less
8. The use of mannitol, bevacizumab, or hormone therapy was allowed before enrollment, but the dose was stable for at least a week without the need for an increment
9. 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 10.Signed the informed consent form prior to patient entry

Exclusion Criteria:

1. Leptomeningeal or hemorrhagic metastases
2. previously used T-dxd
3. Uncontrolled epilepsy
4. 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.
5. History of allergy to treatment regimens
6. Pregnancy or lactation period， women of child-bearing age who are unwilling to accept contraceptive measures.
7. Inability to complete enhanced MRI
8. Not suitable for inclusion for specific reasons judged by sponsor -