Ivonescimab Combined With Chemotherapy for the Treatment of Leptomeningeal Metastases Failed to EGFR-TKIs

January 5, 2025 updated by: Jiangsu Province Nanjing Brain Hospital

Ivonescimab Combined With Chemotherapy for EGFR Mutant NSCLC With Leptomeningeal Metastasis After EGFR TKIs Resistance: A Multicenter Observational Study.

Research objective Main purpose Exploring the real-world effectiveness of Ivonescimab combined with chemotherapy for EGFR mutant NSCLC with leptomeningeal metastasis after EGFR-TKIs resistance. Outcome measure: Real world intracranial disease-free survival time (iPFS).

Secondary purpose Federation patterns: describing different treatment modes in the real world; Outcome measures: Combination chemotherapy regimen and duration of chemotherapy.

Efficacy: Further explore the effectiveness of Ivonescimab combined with chemotherapy for EGFR mutant NSCLC with leptomeningeal metastasis failed with EGFR-TKI treatment; Outcome measures: Objective response rate (LM-ORR), duration of intracranial response (iDoR), overall progression free survival (PFS), overall survival (OS), improvement in neurological function, CSF response rate based on CSF cytology.

Safety: Explore the safety of Ivonescimab combined with chemotherapy for NSCLC patients with leptomeningeal metastases who have failed EGFR-TKI treatment; Outcome measures: incidence of adverse events (TEAEs), laboratory test outliers, and serious adverse events (SAEs).

Research endpoint Primary endpoint

  • iPFS (intracranial progression free survival). Secondary endpoint
  • Efficacy: leptomeningeal ORR (LM-ORR), intracranial duration of response (iDoR), overall progression free survival (PFS), overall survival (OS), improvement in neurological function, and CSF response rate based on CSF cytology;
  • Safety: Determine the incidence and severity of adverse events (AE) and serious adverse events (SAE) according to NCI-CTCAE5.0 standards; Changes in vital signs, laboratory abnormalities, and quality of life scores.

Exploratory endpoint: efficacy related biomarkers

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

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:

  • Age range: 18-75y
  • EGFR mutation NSCLC
  • LM was diagnosed through head enhanced MRI or (and) CSF cytology
  • EGFR activation mutations were positive
  • Patients who have failed to first or second-generation EGFR-TKI treatment，without T790M mutation; or failed to third-generation EGFR-TKI treatment
  • Hematological, coagulation, renal and liver function is sufficient
  • Women of childbearing age must undergo a pregnancy test and the result must be negative

Exclusion Criteria:

  • Patients with squamous cell carcinoma, large cell carcinoma, mixed cell lung cancer
  • The patient has other driver genes that can be treated with targeted drugs
  • Subjects who have previously received immunotherapy with a discontinuation time of less than 3 months
  • Received EGFR-TKI treatment within one week prior to the first administration
  • Received non-specific immunomodulatory therapy
  • Clinical manifestations of neurological failure
  • Non malignant neurological disorders
  • Radiotherapy for the chest and whole brain should be completed within 4 weeks before enrollment
  • Tumor surrounded important blood vessels or had obvious necrosis or cavities
  • Tumor has invaded important surrounding organs and blood vessels
  • History of severe bleeding tendency or coagulation dysfunction
  • The risk of developing esophagotracheal fistula or esophageal pleural fistula

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: Ivonescimab combined with chemotherapy
Drug: Ivonescimab combined with chemotherapy
Ivonescimab combined with chemotherapy. The specific chemotherapy regimen is based on the real world.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
intracranial progression free survival(iPFS)
Time Frame: From enrollment to the end of treatment at 12 months
Treatment initiation to intracranial progression/death/deadline for last follow-up
From enrollment to the end of treatment at 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: From enrollment to the end of treatment at 12 months
Treatment start to PD/death/deadline for last follow-up
From enrollment to the end of treatment at 12 months
OS
Time Frame: From enrollment to the end of treatment at 18 months
The time from randomization to death (for any reason)
From enrollment to the end of treatment at 18 months
iDoR
Time Frame: From enrollment to the end of treatment at 12 months
The time from the first assessment of intracranial lesions as CR or PR to the first assessment as PD or death from any cause
From enrollment to the end of treatment at 12 months

Collaborators and Investigators

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

Sponsor

Jiangsu Province Nanjing Brain Hospital

Collaborators

Henan Cancer Hospital
Three Gorges Hospital of Chongqing 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 (Estimated)

January 1, 2025

Primary Completion (Estimated)

October 31, 2025

Study Completion (Estimated)

October 31, 2025

Study Registration Dates

First Submitted

December 22, 2024

First Submitted That Met QC Criteria

January 5, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 5, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-KY110-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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