Clinical trial NCT06766591: Ivonescimab Combined With Chemotherapy for the Treatment of Leptomeningeal Metastases Failed to EGFR-TKIs
Official title: Ivonescimab Combined With Chemotherapy for EGFR Mutant NSCLC With Leptomeningeal Metastasis After EGFR TKIs Resistance: A Multicenter Observational Study.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: NSCLC
Chemotherapy
Leptomeningeal Metastases
EGFR-TKI
AK112
Keywords: Ivonescimab
NSCLC
leptomeningeal metastases
EGFR-TKI
VEGF
PD-1/VEGF bispecific antibody
Lead sponsor: Jiangsu Province Nanjing Brain Hospital
Sponsor class: OTHER
Collaborators: name: Henan Cancer Hospital
name: Three Gorges Hospital of Chongqing University
First posted: 2025-01-09
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: intracranial progression free survival(iPFS)
timeFrame: From enrollment to the end of treatment at 12 months
Secondary outcomes:
measure: PFS
timeFrame: From enrollment to the end of treatment at 12 months
measure: OS
timeFrame: From enrollment to the end of treatment at 18 months
measure: iDoR
timeFrame: From enrollment to the end of treatment at 12 months
Other outcomes:
Locations:
Study officials:
References:
citation: Cheng WC, Wang G, Mei Q. Ivonescimab Plus Chemotherapy in Patients With EGFR Variant Non-Small Cell Lung Cancer. JAMA. 2025 Jan 14;333(2):172. doi: 10.1001/jama.2024.23088. No abstract available.
citation: Liu Z, Shan D, Han X. Ivonescimab Plus Chemotherapy in Patients With EGFR Variant Non-Small Cell Lung Cancer. JAMA. 2025 Jan 14;333(2):172-173. doi: 10.1001/jama.2024.23091. No abstract available.
citation: Fang W, Li W, Zhang L. Ivonescimab Plus Chemotherapy in Patients With EGFR Variant Non-Small Cell Lung Cancer-Reply. JAMA. 2025 Jan 14;333(2):173-174. doi: 10.1001/jama.2024.23094. No abstract available.
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citation: Dhillon S. Ivonescimab: First Approval. Drugs. 2024 Sep;84(9):1135-1142. doi: 10.1007/s40265-024-02073-w. Epub 2024 Jul 29.
citation: HARMONi-A Study Investigators; Fang W, Zhao Y, Luo Y, Yang R, Huang Y, He Z, Zhao H, Li M, Li K, Song Q, Du X, Sun Y, Li W, Xu F, Wang Z, Yang K, Fan Y, Liu B, Zhao H, Hu Y, Jia L, Xu S, Yi T, Lv D, Lan H, Li M, Liang W, Wang Y, Yang H, Jia Y, Chen Y, Lu J, Feng J, Liu C, Zhou M, Zhou J, Liu X, Zhou N, He M, Dong X, Chen H, Chen Y, Su H, Li X, Zhang Z, Yang L, Cheng Y, Chen L, Hou X, Zhang Y, Guo J, Wang Z, Lu H, Wu D, Feng W, Li W, Huang J, Wang Y, Song X, Peng J, Liu L, Guo Y, Li W, Lu D, Hu M, Wang ZM, Li B, Xia M, Zhang L. Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial. JAMA. 2024 Aug 20;332(7):561-570. doi: 10.1001/jama.2024.10613.
citation: Wang L, Luo Y, Ren S, Zhang Z, Xiong A, Su C, Zhou J, Yu X, Hu Y, Zhang X, Dong X, Meng S, Wu F, Hou X, Dai Y, Song W, Li B, Wang ZM, Xia Y, Zhou C. A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC. J Thorac Oncol. 2024 Mar;19(3):465-475. doi: 10.1016/j.jtho.2023.10.014. Epub 2023 Oct 23.
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