Immune Checkpoint Inhibitor Combined With Pemetrexed Intrathecal Injection for Leptomeningeal Metastasis From Solid Tumors

May 6, 2026 updated by: Zhenyu Pan, Guangzhou Medical University

Immune Checkpoint Inhibitor Combined With Pemetrexed Intrathecal Injection for Leptomeningeal Metastasis From Solid Tumors: a Phase I/II Study

This is an open-label, single-arm, phase I/II trial of immune checkpoint inhibitor combined with pemetrexed intrathecal injection for leptomeningeal metastasis from solid tumors.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, single-arm, phase I/II trial of immune checkpoint inhibitor combined with pemetrexed intrathecal injection for leptomeningeal metastasis from solid tumors. The primary objective was to assess recommended dose and safety based on adverse events (AEs). All participants were observed to evaluate the clinical response rate (CRR), disease control rate (DCR) and overall survival (OS). Patients underwent cerebrospinal fluid (CSF) and blood specimen collection to evaluate potential clinical, molecular, and/or immune predictors of treatment efficacy and safety.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 101100
        • Beijing Chest Hospital, Capital Medical University
      • Beijing, China
        • Cancer Center, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine
    • Guangdong
      • Huizhou, Guangdong, China, 516000
        • The Affiliated Huizhou Hospital, Guangzhou Medical University
      • Huizhou, Guangdong, China
        • Huizhou First Hospital Affiliated to Guangdong Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of solid tumors; Cerebrospinal fluid cytopathology is positive.
  2. Male or female aged between 18 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group
Immune checkpoint inhibitor combined with pemetrexed
Drug: Toripalimab, pemetrexed
Drug 1: Toripalimab 40 mg; Drug 2: pemetrexed 15mg. intrathecal injection therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of treatment-related 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.
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.
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.
Recommended dose
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.]
The recommended dose of intrathecal PD-1 inhibitor. The dose limiting toxicity was defined as ≥ grade 3 neurological toxicities (e.g., chemical meningitis) or other grade 4 toxicity.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurological progression-free survival (NPFS)
Time Frame: From date of treatment until the date of first documented neurological progression or date of death from any cause, whichever came first, assessed up to 6 months.
NPFS was defined as time from the start of treatment until neurological progression or death. The neurological progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.
From date of treatment until the date of first documented neurological progression or date of death from any cause, whichever came first, assessed up to 6 months.
Overall survival(OS)
Time Frame: From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up (at least 7 months).
Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.
From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up (at least 7 months).

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical response rate
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.
The response assessment in neuro-oncology criteria (RANO) proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.
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.
Overall survival(OS)
Time Frame: From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up (at least 7 months).
Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.
From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up (at least 7 months).
Progression-free survival related to leptomeningeal metastasis (LMPFS)
Time Frame: 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.
LMPFS was defined as time from the start of treatment until leptomeningeal metastasis progression or death. The leptomeningeal metastasis progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guangzhou Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2024

Primary Completion (Estimated)

July 31, 2026

Study Completion (Estimated)

July 31, 2026

Study Registration Dates

First Submitted

June 12, 2024

First Submitted That Met QC Criteria

June 12, 2024

First Posted (Actual)

June 17, 2024

Study Record Updates

Last Update Posted (Actual)

May 11, 2026

Last Update Submitted That Met QC Criteria

May 6, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TPLM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All individual participant data that underlie results in a publication will be available to other researchers.

IPD Sharing Time Frame

Starting 6 months after publication

IPD Sharing Access Criteria

Individual participant data will be public accessable via contacting with principal investigator by email within 6 months after the trial complete

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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