Phase II Clinical Trial of Zorifertinib Combined with Ommaya Reservoir-Delivered Intraventricular Pemetrexed for Leptomeningeal Metastasis in EGFR-Mutant NSCLC After Third-Generation EGFR-TKI Failure

Jun 12, 2026 17:59 CST Updated 17:59

Alpha Biopharma

Innovative Drug Developer

Leptomeningeal metastasis (LM) is a severe complication of advanced non-small cell lung cancer (NSCLC), with a particularly high incidence in patients harboring EGFR mutations. Due to the presence of the blood-brain barrier, conventional drugs struggle to achieve effective concentrations in the cerebrospinal fluid. This study aims to explore a novel therapeutic strategy combining the next-generation EGFR-targeted drug lazertinib with intraventricular chemotherapy via an Ommaya reservoir using pemetrexed, for patients who experience leptomeningeal progression after treatment with third-generation EGFR-TKIs, in order to provide more effective treatment options for this patient population. To evaluate the preliminary efficacy and safety of this regimen, Professor Wan Jinghai from the Department of Neurosurgery at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital of the Chinese Academy of Medical Sciences has initiated this clinical trial and is now publicly recruiting eligible patients.

Research Introduction

Indications:Leptomeningeal Metastasis Following Treatment of Non-Small Cell Lung Cancer with Third-Generation EGFR-TKIs

Treatment Plan:Zolifitinib Combined with Intraventricular Chemotherapy via Ommaya Reservoir

Research Objective:Evaluate the preliminary efficacy and safety of this regimen

Study Design:Open-label, single-arm, single-center, prospective

Research Phase:Phase II

This study (NCC6051) was funded by Alpha Biopharma, and conducted byThe Neurosurgery Team of Professor Wan Jinghai at the Cancer Hospital, Chinese Academy of Medical Sciences(PI)-initiated, and has currently been approved by the Medical Ethics Committee of the Cancer Hospital of the Chinese Academy of Medical Sciences.

Major Inclusion Criteria

①Informed Consent: Voluntary participation and signing of the informed consent form, aged 18-75 years;

②Definite Diagnosis: Pathologically confirmed NSCLC with EGFR sensitizing mutations (L858R and/or Exon 19 deletion);

③Treatment History and Pattern of Progression: After prior treatment with third-generation EGFR-TKIs, leptomeningeal progression occurred, but extracranial lesions did not progress;

④Diagnosis of Leptomeningeal Metastasis: Positive cerebrospinal fluid cytology, or a clinical diagnosis of leptomeningeal metastasis based on clinical symptoms and brain/spinal cord MRI imaging findings;

⑤Ommaya Reservoir Status: The Ommaya reservoir has been successfully implanted, with normal reservoir function and no surgery-related complications.

⑥Physical Condition: Karnofsky Performance Status (KPS) ≥ 60, with an expected survival time of ≥ 3 months;

⑦Organ Function: Major laboratory test indicators, including complete blood count and liver and kidney function, meet the study requirements.

Registration and Inquiry Information

If you or your family members wish to learn more about the study details or assess eligibility, please contact the research team:

Contact:Dr. Cai Hongqing (SubPI)

Contact Information / Visit Information:

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Department of Neurosurgery (General Outpatient Clinic on Monday Afternoons; Online Consultation on Thursdays)

Introduction of the Principal Investigator

Professor Wan Jinghai

Cancer Hospital, Chinese Academy of Medical Sciences

Director of the Department of Neurosurgery, Chief Physician, Professor, and Doctoral Supervisor at the Cancer Hospital of the Chinese Academy of Medical Sciences (National Cancer Center)
Chairman of the Committee on Neuro-Oncology, China Anti-Cancer Association
Vice Chairman of the Neuro-Oncology Expert Committee, Chinese Society of Clinical Oncology (CSCO)
President-Elect, Committee on Neuro-Oncology, Beijing Association of Cancer
Standing Committee Member, Skull Base Surgery Professional Committee, Chinese Medical Promotion Association
Member of the Neuroendoscopy Committee and the Brain Glioma Committee, Chinese Medical Doctor Association

Scan the QR code to proceedProfessor Jinghai WanAcademic Homepage

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