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

Not Applicable

Not yet recruiting

• Conditions: NSCLC; Chemotherapy; Leptomeningeal Metastases; EGFR-TKI; AK112
• Interventions: Drug: Ivonescimab combined with chemotherapy

• Registration Number: NCT06766591
• Lead Sponsor: Jiangsu Province Nanjing Brain Hospital

Brief 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-22
• Status Verified: 2025-01
• Study Start: 2025-01-01
• Study First Submitted QC: 2025-01-05
• Last Update Submitted: 2025-01-05
• Study First Posted: 2025-01-09
• Last Update Posted: 2025-01-09
• Primary Completion: 2025-10-31
• Study Completion: 2025-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 36

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ivonescimab combined with chemotherapy	Ivonescimab combined with chemotherapy	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
PFS	From enrollment to the end of treatment at 12 months	Treatment start to PD/death/deadline for last follow-up
OS	From enrollment to the end of treatment at 18 months	The time from randomization to death (for any reason)
iDoR	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