Clinical trial · Interventional
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Intrathecal Drug Delivery | — | UNRESOLVED | — |
| Leptomeningeal Metastasis | Meningeal Carcinomatosis | PROBABILISTIC | 0.70 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| AK112 | Drug | — | UNRESOLVED |
| Pemetrexed (Alimta) | Drug | Pemetrexed | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Intrathecal PD-1/VEGF Bispecific Antibody plus Pemetrexed
- description
- This study is a prospective, single-arm, Phase I/II clinical trial. The primary objective is to determine the recommended Phase II dose (RP2D) for the intrathecal combination of PD-1/VEGF bispecific antibody with pemetrexed and and safety based on the incidence of treatment-related adverse events. Clinical response rate (CRR), progression-free survival related to leptomeningeal metastasis (LMPFS) and overall survival (OS) are also evaluated. Patients will have cerebrospinal fluid (CSF) and blood specimen collection for the evaluation of predictors (clinical, molecular, and/or immune) of the efficacy and safety of this regimen.
- interventionNames
- Drug: AK112
- Drug: Pemetrexed (Alimta)
Primary outcomes (2)
- measure
- PR2D
- timeFrame
- From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
- description
- The recommended phase II dose. The dose limiting toxicity was defined as ≥ grade 3 neurological toxicities (e.g., chemical meningitis) or other grade 4 toxicity.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 21 Years
- Maximum age
- 75 Years
Show eligibility criteria text
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.
References
Publications (0)
Data not yet available