Using dual checkpoint inhibitors with pemetrexed for leptomeningeal metastasis treatment

Intrathecal Administration of Dual Checkpoint Inhibitor in Combination With Pemetrexed in Patients With Leptomeningeal Metastasis: a Phase I/II Study

This study is testing a new treatment combining two immune therapies with a cancer drug to see if it helps 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 (other)
• Locations: 2 sites (Huizhou, Guangdong and 1 other locations)
• Trial ID: NCT06809530 on ClinicalTrials.gov

What this trial studies

This phase I/II clinical trial evaluates the safety, feasibility, and therapeutic response of an intrathecal dual checkpoint inhibitor targeting PD-1 and CTLA-4, combined with pemetrexed, in patients with leptomeningeal metastasis. The treatment involves administering intrathecal pemetrexed and the bispecific antibody QL1706 in a structured regimen over several weeks. The study aims to determine the recommended dose of QL1706 and assess treatment-related adverse events, clinical response rates, progression-free survival, and overall survival. Additionally, cerebrospinal fluid and blood samples will be collected to identify potential predictors of treatment efficacy and safety.

Who should consider this trial

Good fit: Ideal candidates are adults aged 21 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 approach could provide a novel treatment option for patients suffering from leptomeningeal metastasis, potentially improving survival outcomes.

How similar studies have performed: While the use of checkpoint inhibitors has shown promise in various cancers, this specific combination approach is novel and has not been extensively tested in similar settings.

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. 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. Patients with poor compliance or other reasons that were unsuitable for this study.

Where this trial is running

Huizhou, Guangdong and 1 other locations

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

Conditions: Leptomeningeal Metastasis, Pemetrexed, PD-1 Inhibitor, CTLA4, Solid Tumors, Leptomeningeal metastasis, dual checkpoint inhibitor, pemetrexed