Treatment for leptomeningeal metastasis using a bispecific antibody and chemotherapy

A Phase I/II Clinical Study of Intrathecal Combination Therapy With the PD-1/VEGF Bispecific Antibody and Pemetrexed for Leptomeningeal Metastasis

This study is testing a new treatment that combines a special antibody and chemotherapy to see if it can help people with leptomeningeal metastasis feel better and live longer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 21 Years to 75 Years
• Sex: All
• Sponsor: Guangzhou Medical University (Academic / other)
• Drugs / interventions: Osimertinib, Lorlatinib, ivonescimab, chemotherapy, immunotherapy
• Locations: 1 site (Huizhou, Guangdong)
• Trial ID: NCT06809517 on ClinicalTrials.gov

What this trial studies

This phase I/II clinical trial evaluates the safety, feasibility, and therapeutic response of an intrathecal PD-1/VEGF bispecific antibody combined with pemetrexed in patients suffering from leptomeningeal metastasis. The study aims to determine the recommended dosage of the bispecific antibody, ivonescimab, and assess its effectiveness in improving clinical outcomes such as progression-free survival and overall survival. Participants will undergo cerebrospinal fluid and blood specimen collection to identify potential predictors of treatment efficacy and safety. The trial builds on preliminary findings suggesting that this combination therapy may offer a new approach to treating this severe complication of advanced malignancies.

Who should consider this trial

Good fit: Ideal candidates include adults aged 21 to 75 with confirmed solid tumors and positive cerebrospinal fluid cytopathology.

Not a fit: Patients with severe nervous system diseases, extensive systemic diseases without effective treatment, or significant bleeding tendencies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel therapeutic option for patients with leptomeningeal metastasis, potentially improving survival rates and quality of life.

How similar studies have performed: While this approach is novel, preliminary studies have indicated safety and feasibility for similar treatments in this patient population.

Eligibility criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of solid tumors;Cerebrospinal fluid cytopathology is positive.
2. Male or female aged between 21 and 75 years; Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3.
3. No history of severe nervous system disease; No severe dyscrasia.

Exclusion Criteria:

1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.
2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment.
3. Obvious bleeding tendency; Patients with hemorrhage (NCI-CTCAE v5.0 greater than grade 2), coagulation disorder, hypertensive crisis, and severe arterial thrombosis.
4. 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.
5. 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.
6. Patients with poor compliance or other reasons that were unsuitable for this 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, PhD,MD — The Affiliated HuizhouHospital, Guangzhou Medical University
• Study coordinator: Zhenyu Pan, PhD, MD

Conditions Leptomeningeal Metastasis; Intrathecal Drug Delivery; Leptomeningeal metastasis; PD-1/VEGF Bispecific Antibody; Pemetrexed