Combining a bispecific antibody and chemotherapy for leptomeningeal metastasis treatment

Intrathecal Administration of PD-1/CTLA-4 Bispecific Antibody Plus Pemetrexed in Patients With Leptomeningeal Metastasis From Solid Tumors: A Phase I/II Study

This study is testing a new combination of 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: 36 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Guangzhou Medical University (Academic / other)
• Drugs / interventions: Osimertinib, Lorlatinib, Cadonilimab, chemotherapy, immunotherapy
• Locations: 1 site (Huizhou, Guangdong)
• Trial ID: NCT06762080 on ClinicalTrials.gov

What this trial studies

This phase I/II clinical trial evaluates the safety, feasibility, and therapeutic response of an intrathecal combination of a PD-1/CTLA-4 bispecific antibody (cadonilimab) and pemetrexed in patients with leptomeningeal metastasis. The study aims to determine the recommended dosage and assess treatment-related adverse events while also measuring clinical response rates and overall survival. Patients will undergo cerebrospinal fluid and blood specimen collection to identify potential predictors of treatment efficacy and safety. The trial is based on promising preliminary results from previous studies indicating the safety and potential effectiveness of this combination therapy.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 75 with confirmed solid tumors and positive cerebrospinal fluid cytopathology.

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

Why it matters

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

How similar studies have performed: Previous studies have shown promising results with similar immunotherapy approaches, indicating potential efficacy in treating leptomeningeal metastasis.

Eligibility criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of solid tumors; Cerebrospinal fluid cytopathology is positive.
2. Male or female aged between 18 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. 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.
4. 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.
5. 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 Huizhou Hospital, Guangzhou Medical University
• Study coordinator: Zhenyu Pan, PhD, MD

Conditions Leptomeningeal Metastasis; Cadonilimab; PD-1/CTLA-4; Pemetrexed; Intrathecal