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

NCT ID: NCT06809530

Last Updated: 2025-05-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-17
• Study Completion Date: 2026-07-01

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intrathecal Dual Checkpoint Inhibition in Combination with Pemetrexed

This study is a prospective, single-arm, Phase I/II clinical trial. The primary objectives were to determine the recommended dose of intrathecal dual checkpoint inhibitor (PD-1 and CTLA-4, QL1706) in combination with pemetrexed 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.

Group Type: EXPERIMENTAL

Pemetrexed (Alimta)

Intervention Type: DRUG

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.

QL1706 (bispecific antibody targeting PD-1 and CLTA-4)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Zhenyu Pan

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhenyu Pan, PhD,MD

Role: PRINCIPAL_INVESTIGATOR

The Affiliated HuizhouHospital, Guangzhou Medical University

Locations

The Affiliated Huizhou Hospital, Guangzhou Medical University

Huizhou, Guangdong, China

Site Status: RECRUITING

The Affiliated Huizhou Hospital, Guangzhou Medical University

Huizhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhenyu Pan

Role: CONTACT

dr-zypan@163.com

+8618718178286

Guozi Yang, PhD,MD

Role: CONTACT

2023621057@gzhmu.edu.cn

+8615804302755

Facility Contacts

Zhenyu Pan, PhD,MD

Role: primary

dr-zypan@163.com

+8618718178286

Guozi Yang, PhD,MD

Role: backup

2023621057@gzhmu.edu.cn

+8615804302755

Other Identifiers

IT-P-QL1706

Identifier Type: -

Identifier Source: org_study_id