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

Jiangsu Province Nanjing Brain Hospital

Status

Not yet enrolling

Conditions

Chemotherapy

EGFR-TKI

AK112

Leptomeningeal Metastases

NSCLC

Treatments

Drug: Ivonescimab combined with chemotherapy

Study type

Interventional

Funder types

Other

Identifiers

NCT06766591

2024-KY110-01

Details and patient eligibility

About

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

Enrollment

36 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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