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

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.