NCT06809530

Intrathecal Dual Checkpoint Inhibitor (PD-1 and CTLA-4) in Combination With Pemetrexed for Leptomeningeal Metastasis

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

• 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

This phase I/II study is to evaluate the recommended dose, safety, feasibility, and therapeutic response of intrathecal dual checkpoint inhibitor (targeting PD-1 and CTLA-4 with QL1706) in combination with pemetrexed in patients with leptomeningeal metastasis.

Detailed description

This study is a prospective, single-arm, phase I/II clinical trial evaluating intrathecal dual checkpoint inhibitor (targeting PD-1 and CTLA-4 with the bispecific antibody QL1706) in combination with pemetrexed for the treatment of leptomeningeal metastasis. Intrathecal pemetrexed is administered twice weekly for 2 weeks (induction phase), then weekly for 4 weeks (consolidation phase), and monthly thereafter (maintenance phase). Intrathecal QL1706 (a PD-1/CTLA-4 bispecific antibody) is given every two weeks during the six-week induction phase, followed by monthly injections in the maintenance phase, until disease progression or death. The primary objectives are to determine the recommended dose of intrathecal QL1706 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
• Pemetrexed
• PD-1 Inhibitor
• CTLA4
• Solid Tumors

Interventions

Type	Name	Description
DRUG	QL1706 (bispecific antibody targeting PD-1 and CLTA-4)	Intrathecal injection of PD-1/CTLA-4 bispecific antibody was administered every 2 weeks for 6 weeks during the induction phase, followed by monthly injections during the maintenance phase, until recurrence or death.
DRUG	Pemetrexed (Alimta)	Pemetrexed (Alimta, Eli Lilly and Company) 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: 2025-03-17
• Primary completion: 2026-06-01
• Completion: 2026-07-01
• First posted: 2025-02-05
• Last updated: 2025-05-18

Locations

2 sites across 1 country: China