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

N/ANot Yet RecruitingNCT06766591

Jiangsu Province Nanjing Brain Hospital36 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

intracranial progression free survival(iPFS)

Treatment initiation to intracranial progression/death/deadline for last follow-up

Time frame: From enrollment to the end of treatment at 12 months

Secondary Outcomes

PFS

Treatment start to PD/death/deadline for last follow-up

Time frame: From enrollment to the end of treatment at 12 months

The time from randomization to death (for any reason)

Time frame: From enrollment to the end of treatment at 18 months

iDoR

The time from the first assessment of intracranial lesions as CR or PR to the first assessment as PD or death from any cause

Time frame: From enrollment to the end of treatment at 12 months

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts