NCT06762080

Intrathecal Combination of Programmed Death-1 (PD-1)/Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Bispecific Antibody and Pemetrexed for Leptomeningeal Metastasis

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Guangzhou Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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 Programmed Death-1 (PD-1)/Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) bispecific antibodies combined with pemetrexed in patients with leptomeningeal metastasis.

Detailed description

Leptomeningeal metastasis is a severe complication of advanced cancer, traditionally managed with intrathecal chemotherapy. Recently, immunotherapy has emerged as a promising treatment for solid tumors. The preliminary results from our previous study on PD-1 combined with pemetrexed intrathecal administration showed safety and feasibility for leptomeningeal metastasis from solid tumors with potential activity. Currently, a clinical trial in Switzerland is evaluating the efficacy of dual immunotherapy (PD-1 plus CTLA-4 inhibitors) administered intrathecally for leptomeningeal metastasis. Cadonilimab, the world's first PD-1/CTLA-4 bispecific antibody, has shown favorable safety and efficacy in clinical practice, further supporting its potential in this setting. The primary objectives are to determine the recommended dose of intrathecal cadonilimab in combination with pemetrexed and to assess safety based on the incidence of treatment-related adverse events. Clinical response rate, progression-free survival related to leptomeningeal metastasis, and overall survival are also evaluated. Patients undergo cerebrospinal fluid and blood specimen collection to evaluate potential clinical, molecular, and/or immune predictors of treatment efficacy and safety.

Conditions

• Leptomeningeal Metastasis

Interventions

Type	Name	Description
DRUG	Cadonilimab (AK104)	Intrathecal injection of PD-1/CTLA-4 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.
DRUG	Pemetrexed (Alimta)	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.

Timeline

• Start date: 2025-03-07
• Primary completion: 2026-01-01
• Completion: 2026-06-01
• First posted: 2025-01-07
• Last updated: 2025-05-20

Locations

1 site across 1 country: China