Sacituzumab govitecan plus intrathecal pemetrexed for leptomeningeal metastases from HER2-negative breast cancer

A Phase I/II Clinical Study of Sacituzumab Govitecan Combined With Intrathecal Chemotherapy for the Treatment of Leptomeningeal Metastases From Her2-negative Breast Cancer

This tests whether sacituzumab govitecan combined with intrathecal pemetrexed can help people with leptomeningeal metastases from HER2-negative breast cancer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Guangzhou Medical University (Academic / other)
• Drugs / interventions: Sacituzumab, chemotherapy
• Locations: 1 site (Huizhou, Guangdong)
• Trial ID: NCT06462092 on ClinicalTrials.gov

What this trial studies

This single-arm Phase I/II trial gives intravenous sacituzumab govitecan (10 mg/kg on Days 1 and 8 of a 21-day cycle) together with intrathecal pemetrexed delivered via lumbar puncture or intracerebroventricular access. Intrathecal pemetrexed is administered in an induction phase (15 mg twice weekly for 2 weeks), a consolidation phase (once weekly for 4 weeks), and maintenance (once monthly for responders), with systemic therapy continued until progression or unacceptable toxicity. Phase I enrolled 3–6 patients to monitor dose-limiting toxicities and allowed a reduction of the intrathecal dose to 10 mg if toxicity thresholds were met before moving to Phase II. The trial focuses primarily on safety and feasibility with secondary evaluation of clinical and radiographic activity against leptomeningeal disease.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed HER2-negative breast cancer and leptomeningeal metastases documented by CSF cytology or compatible imaging plus clinical signs are the intended participants.

Not a fit: Patients with inadequate blood counts or liver function, serious uncontrolled comorbidities, known immunodeficiency, pregnancy or breastfeeding, or inability to tolerate intrathecal procedures are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could improve control of leptomeningeal disease and extend survival or preserve neurological function for affected patients.

How similar studies have performed: Sacituzumab govitecan has established systemic benefit in HER2-negative metastatic breast cancer and intrathecal pemetrexed has shown activity in small series, but combining the two for leptomeningeal disease is novel and not yet validated in large trials.

Eligibility criteria

Inclusion Criteria:

1. A clear histopathologic diagnosis of breast cancer with HER2-negative subtype (including IHC 0, IHC 1+ or IHC 2+ and ISH negative);
2. 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;
3. Age ≥ 18 years old.

Exclusion Criteria:

1. 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;
2. 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;
3. Pregnant and breastfeeding female patients; women of childbearing age who are unwilling or unable to use effective contraception;
4. Any other condition that, in the opinion of the investigator, makes the patient ineligible for participation in the study.

Where this trial is running

Huizhou, Guangdong

• The Affiliated Huizhou Hospital, Guangzhou Medical University — Huizhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Zhenyu Pan — Huizhou Hospital of Guangzhou Medical University
• Study coordinator: Zhenyu Pan

Conditions Leptomeningeal Metastases; Breast cancer; Her2-; Sacituzumab Govitecan; Pemetrexed; Intrathecal chemotherapy