NCT06809517

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Sponsor: Guangzhou Medical University · Academic / Other
• Sex: All
• Age: 21 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 PD-1/VEGF bispecific antibody plus pemetrexed in patients with leptomeningeal metastasis.

Detailed description

Leptomeningeal metastasis represents a severe complication of advanced malignancies, for which intrathecal chemotherapy remains the mainstay treatment. 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. In recent years, targeted therapy and immunotherapy has been widely used for the treatment of solid tumors. As the world's first PD-1/VEGF bispecific antibody, ivonescimab ((AK112) has shown superior systemic efficacy compared to conventional VEGF targeted therapy combined with immunotherapy, while maintaining a favorable safety profile. The primary objectives are to determine the recommended dose of intrathecal ivonescimab 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
• Intrathecal Drug Delivery

Interventions

Type	Name	Description
DRUG	AK112	Intrathecal injection of PD-1/VEGF 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: 2025-03-18
• Primary completion: 2026-03-01
• Completion: 2026-05-01
• First posted: 2025-02-05
• Last updated: 2025-05-20

Locations

1 site across 1 country: China