Clinical trial NCT06809530: Intrathecal Dual Checkpoint Inhibitor (PD-1 and CTLA-4) in Combination With Pemetrexed for Leptomeningeal Metastasis
Official title: Intrathecal Administration of Dual Checkpoint Inhibitor in Combination With Pemetrexed in Patients With Leptomeningeal Metastasis: a Phase I/II Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Leptomeningeal Metastasis
Pemetrexed
PD-1 Inhibitor
CTLA4
Solid Tumors
Keywords: Leptomeningeal metastasis
dual checkpoint inhibitor
pemetrexed
Lead sponsor: Guangzhou Medical University
Sponsor class: OTHER
First posted: 2025-02-05
Enrollment: 34
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: PR2D
timeFrame: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
measure: Incidence of treatment-related adverse events
timeFrame: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
Secondary outcomes:
Other outcomes:
measure: Clinical response rate
timeFrame: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
measure: Progression-free survival related to leptomeningeal metastasis (LMPFS)
timeFrame: From date of treatment until the date of first documented leptomeningeal metastasis progression or date of death from any cause, whichever came first, assessed up to 6 months
measure: Overall survival(OS)
timeFrame: From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up, assessed up to 6 months.
Locations:
city: Huizhou
country: China
facility: The Affiliated Huizhou Hospital, Guangzhou Medical University
state: Guangdong
city: Huizhou
country: China
facility: The Affiliated Huizhou Hospital, Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: The Affiliated HuizhouHospital, Guangzhou Medical University
name: Zhenyu Pan, PhD,MD
role: PRINCIPAL_INVESTIGATOR
References: