Intrathecal PD-1/VEGF Bispecific Antibody Plus Pemetrexed for Leptomeningeal Metastasis
A Phase I/II Clinical Study of Intrathecal Combination Therapy With the PD-1/VEGF Bispecific Antibody and Pemetrexed for Leptomeningeal Metastasis
Guangzhou Medical University
34 participants
Mar 18, 2025
INTERVENTIONAL
Conditions
Summary
Leptomeningeal metastasis, characterized by tumor cells infiltrating and proliferating in the subarachnoid space, represents a distinct pattern of central nervous system involvement and is a fatal complication of malignant tumors. This phase I/II study is to evaluate the recommended dose, safety, feasibility, and therapeutic response of intrathecal PD-1/VEGF bispecific antibody plus pemetrexed in patients with leptomeningeal metastasis.
Eligibility
Inclusion Criteria3
- Histologically or cytologically confirmed diagnosis of solid tumors;Cerebrospinal fluid cytopathology is positive.
- Male or female aged between 21 and 75 years; Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3.
- No history of severe nervous system disease; No severe dyscrasia.
Exclusion Criteria6
- Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.
- Any evidence of extensive and lethal progressive systemic diseases without effective treatment.
- Obvious bleeding tendency; Patients with hemorrhage (NCI-CTCAE v5.0 greater than grade 2), coagulation disorder, hypertensive crisis, and severe arterial thrombosis.
- A history of HIV or AIDS, acute or chronic hepatitis B or C infection, previous anti-PD1 therapy-induced pneumonitis, or have ongoing >Grade 2 adverse events of such therapy; or ongoing autoimmune disease that required systemic treatment in the past 2 years.
- The first month to treatment, as well as during induction and consolidation therapy, new drugs effective against leptomeningeal metastases were used, excluding those previously administered. These primarily included small molecule targeted therapies, such as EGFR-TKI/ALK-TKI drugs like Osimertinib and Lorlatinib.
- Patients with poor compliance or other reasons that were unsuitable for this study.
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Interventions
Intrathecal injection of PD-1/VEGF bispecific antibody was administered every two weeks for six weeks during the induction phase, followed by monthly injections during the maintenance phase, until recurrence or death.
Pemetrexed was administrated by intrathecal injection, first as induction therapy, twice per week for 2 weeks, followed by consolidation therapy, once per week for 4 weeks, then maintenance therapy, once per month until the patient's death, leptomeningeal metastasis progresses, or intolerable severe adverse events occurred.
Locations(1)
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NCT06809517