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

Phase 2RecruitingNCT06809530

Guangzhou Medical University34 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Leptomeningeal Metastasis

Interventions

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

Pemetrexed (Alimta)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.

Eligibility

Sex: ALLMin age: 21 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

PR2D

The recommended phase II dose. The dose limiting toxicity was defined as ≥ grade 3 neurological toxicities (e.g., chemical meningitis) or other grade 4 toxicity.

Time frame: 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

Incidence of treatment-related adverse events

The incidence of treatment-related adverse events were measured for determining tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). Events of grade 3-5 are defined as moderate and severe adverse events.

Time frame: 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.