Sacituzumab Govitecan and Intrathecal Chemotherapy for Treating Leptomeningeal Metastases From Her2-negative Breast Cancer

This study is a single-arm, prospective Phase I/II clinical trial, evaluating the safety, feasibility, and potential efficacy of combining Sacituzumab Govitecan with intrathecal pemetrexed chemotherapy for leptomeningeal metastases from HER2-negative breast cancer. The treatment regimen includes intravenous administration of Sacituzumab Govitecan (10 mg/kg) on Days 1 and 8 of each 21-day cycle, continuing until disease progression or unacceptable toxicity. Intrathecal pemetrexed chemotherapy is initiated on Day 2 via intracerebroventricular or lumbar puncture. The treatment is divided into three phases: induction therapy, 15 mg twice weekly for 2 weeks; consolidation therapy, once weekly for 4 weeks; maintenance therapy, once monthly for patients with an effective response until relapse or death. In the Phase I cohort, 3-6 patients were enrolled. If dose-limiting toxicity (DLT) occurred in ≥2 patients, the intrathecal dose of pemetrexed was reduced to 10 mg, and enrollment continued to ensure a total of 6 evaluable patients. If DLT recurred in ≥2 patients among the subsequently enrolled patients, the trial would be terminated. If DLT occurred in ≤1 patient, the trial would proceed to Phase II.

Inclusion criteria

• A clear histopathologic diagnosis of breast cancer with HER2-negative subtype (including IHC 0, IHC 1+ or IHC 2+ and ISH negative);
• Cerebrospinal fluid cytology confirms the presence of leptomeningeal metastases; or imaging findings combined with clinical symptoms and signs are consistent with the diagnosis of leptomeningeal metastases;
• Age ≥ 18 years old.

Exclusion criteria

• Inadequate organ function: 1) Blood tests: ANC ≤ 1.5 x 10^9/L, PLT ≤ 90 x 10^9/L, Hb ≤ 90 g/L; 2) Blood biochemistry tests: TBIL ≥ 1.5 times the upper limit of normal; 3) ALT and AST ≥ 2.5 times the upper limit of normal;
• Presence of serious and/or uncontrolled comorbidities that may affect participation: 1) Allergy to study drugs or adjuvant materials; 2) History of immunodeficiency (e.g., HIV-positive or other acquired or congenital immunodeficiency disease); 3) Severe concomitant diseases;
• Pregnant and breastfeeding female patients; women of childbearing age who are unwilling or unable to use effective contraception;
• Any other condition that, in the opinion of the investigator, makes the patient ineligible for participation in the study.