ivonescimab combined with chemotherapy for the treatment of leptomeningeal metastases failed to egfr-tkis

Conditions: NSCLC; Chemotherapy; Leptomeningeal Metastases; EGFR-TKI; AK112

Summary: 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


Eligibility 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

Keywords: ivonescimab nsclc leptomeningeal metastases egfr-tki vegf pd-1/vegf bispecific antibody