Phase I/II Study of Intrathecal/Ommaya T-DXd in HER2-Expressing Breast Cancer With Leptomeningeal/Brain Metastases

Inclusion Criteria: * Age ≥18 years, regardless of gender. * HER2-expressing advanced or metastatic breast cancer * Leptomeningeal metastasis * Subjects with active brain metastases only must have at least one intracranially measurable lesion (RANO-BM criteria). * Adequate organ and bone marrow function * No radiotherapy, chemotherapy, targeted therapy, immunotherapy, endocrine therapy, or surgery within 2 weeks prior to enrollment (or within 5 half-lives of prior therapy, whichever is shorter). * All prior treatment-related toxicities must have resolved to ≤Grade 1 Exclusion Criteria: * Diagnosis of other malignancies within the past 5 years, except for cured carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin, other in situ carcinomas, or papillary thyroid carcinoma. * Uncontrolled concurrent illnesses including, but not limited to: persistent or active infections, uncontrolled or clinically significant cardiovascular diseases, severe chronic gastrointestinal disorders with diarrhea, or psychiatric/social conditions that may compromise compliance with study requirements, significantly increase AE risks, or impair the subject's ability to provide written informed consent. * History of (non-infectious) ILD/non-infectious pneumonitis requiring steroid therapy, current ILD/non-infectious pneumonitis, or suspected ILD/non-infectious pneumonitis that cannot be ruled out by imaging during screening. * Clinically significant pulmonary comorbidities * Use of immunosuppressants or systemic corticosteroids (\>10 mg/day prednisone equivalent) for immunosuppression within 2 weeks prior to first dose (excluding intranasal/inhaled corticosteroids). * Any active autoimmune disease or history of autoimmune disease with potential recurrence. * Uncontrolled infections requiring IV antibiotics, antivirals, or antifungals. * Active primary immunodeficiency, known HIV infection, active HBV (HBsAg+ with HBV DNA ≥500 IU/mL) or HCV infection. HCV antibody-positive subjects are eligible only if PCR confirms HCV RNA negativity. * Radiographic evidence of tumor encasement/invasion of major blood vessels, or investigator-determined high risk of fatal hemorrhage due to probable vascular invasion during treatment. * Pregnant/lactating women, or subjects of reproductive potential unwilling/unable to use effective contraception. * Any other condition deemed by investigators to potentially affect trial conduct or outcome interpretation.