A Phase II Observational Clinical Study on the Relationship Between Cerebrospinal Fluid Drug Concentration and Efficacy of Trastuzumab Deruxtecan in Central Nervous System Metastatic Breast Cancer

Exclusion Criteria18

• \. Presence of uncontrolled third-space fluid accumulation (e.g., large pleural effusion or ascites) not manageable by drainage or other methods, deemed unsuitable for enrollment by the investigator.
• \. Previous treatment with an anti-HER2 ADC drug carrying the same payload resulting in resistance. Patients who discontinued prior ADC therapy for other reasons, including but not limited to toxicity, are eligible.
• \. Adverse reactions from prior anti-tumor therapy have not recovered to ≤ Grade 1 per CTCAE v5.0 (except for ≤ Grade 2 toxicities judged by the investigator as having no safety risk, such as alopecia or long-term toxicities from radiotherapy).
• \. History of other malignancies within the past 5 years, excluding cured carcinoma in situ of the cervix, basocellular skin carcinomas, or cutaneous squamous cell carcinoma.
• \. History of severe cardiovascular or cerebrovascular diseases, including but not limited to:
• Severe cardiac rhythm or conduction abnormalities requiring clinical intervention, such as ventricular arrhythmia, II-III degree atrioventricular block, etc.
• Cardiac insufficiency of Class III~IV according to the New York Heart Association (NYHA) criteria.
• Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade 3 or higher cardiovascular/cerebrovascular events within 6 months prior to the first dose.
• Clinically uncontrolled hypertension.
• Any factors increasing the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, use of any concomitant medications known or suspected to prolong the QT interval; Known history of allergy to any component of the study drug.
• \. History of immunodeficiency disease, including other acquired or congenital immunodeficiency diseases, history of organ transplantation, allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation.
• \. HIV infection, active HBV or HCV infection. The following exceptions are allowed:
• Patients positive for hepatitis B surface antigen (HBsAg), with or without positive hepatitis B core antibody (anti-HBc), if HBV DNA < 1000 IU/mL or below the lower limit of detection at the research center, and per investigator assessment excluding active infection based on clinical treatment and presentation.
• Hepatitis C (HCV) antibody-positive patients who are HCV RNA-negative. 8. History of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis, or glomerulonephritis, except for autoimmune thyroid dysfunction treated with stable-dose hormone replacement therapy.
• \. Patients with known idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, interstitial lung disease, severe radiation pneumonitis, or evidence of active pneumonia on screening chest CT scan.
• \. Inability to cooperate with lumbar puncture. 11. Vaccination with any vaccine within 28 days prior to the first dose. 12. Pregnant or lactating female patients; female patients of childbearing potential with baseline pregnancy test positive; or patients unwilling to use effective contraception throughout the trial period.
• \. Presence of any concomitant disease, per investigator judgment, that seriously endangers the patient's safety or affects the patient's ability to complete the study (including but not limited to severe hypertension that cannot be controlled by medication, severe diabetes, active infection, thyroid disease, etc.).
• \. Any other circumstances where the researcher deems the patient unsuitable for participation in this study.