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

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

Study Purpose

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

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 75 Years
Gender	All

More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06766591
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Jiangsu Province Nanjing Brain Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	NSCLC, Chemotherapy, Leptomeningeal Metastases, EGFR-TKI, AK112