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

Guangzhou Medical University

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: CTLA4; Pemetrexed; Leptomeningeal Metastasis; PD-1 Inhibitor; Solid Tumors

Treatments: Drug: QL1706 (bispecific antibody targeting PD-1 and CLTA-4); Drug: Pemetrexed (Alimta)

Study type: Interventional

Funder types: Other

Identifiers

NCT06809530

IT-P-QL1706

Details and patient eligibility

About

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.

Full 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.

Enrollment: 34 estimated patients

Sex: All

Ages: 21 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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34 participants in 1 patient group

Intrathecal Dual Checkpoint Inhibition in Combination with Pemetrexed

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed (Alimta)

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