Combining Furmonertinib with Chemotherapy for Advanced Lung Cancer with Brain Metastasis

A Single-arm, Prospective Clinical Study of Double Dose of Furmonertinib Combined With Lateral Ventricular Chemotherapy in the Treatment of EGFR-mutant Lung Cancer With Leptomeningeal Metastasis After Third-generation EGFR-TKIs Resistance

This study is testing if combining a new drug called Furmonertinib with chemotherapy can help people with advanced lung cancer that has spread to the brain feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Jiangsu Province Nanjing Brain Hospital (Academic / other)
• Drugs / interventions: vormetinib, Furmonertinib, chemotherapy
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06339242 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of Furmonertinib in combination with lateral ventricle chemotherapy for patients with non-small cell lung cancer (NSCLC) who have developed leptomeningeal metastasis after resistance to third-generation EGFR-TKIs. The approach aims to improve progression-free survival in these patients by leveraging the unique properties of Furmonertinib, which can penetrate the blood-brain barrier. The study will involve patients aged 18-75 with confirmed EGFR mutations and will assess both neurological symptoms and overall survival outcomes. This is a Phase 2 interventional trial, focusing on a population that currently lacks effective treatment options.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with EGFR mutation-positive NSCLC and leptomeningeal metastasis after resistance to third-generation EGFR-TKIs.

Not a fit: Patients with severe liver or kidney dysfunction or other serious chronic diseases may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival and quality of life for patients with advanced NSCLC and leptomeningeal metastasis.

How similar studies have performed: While there is limited evidence from prospective trials, previous studies have shown promising results with similar treatment approaches, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* aged 18-75 years old (including 18 and 75 years old);
* ECOG PS 0-3 with no deterioration in the first 2 weeks；
* The lowest expected survival time was ≥12 weeks；
* NSCLC patients with EGFR sensitive mutations confirmed by tissue and/or cytology;
* Patients with EGFR sensitive mutations (EGFR exon 19 deletion or EGFR exon 21 L858R mutation) without other driver genes with targeted therapy (such as C797X mutation, MET abnormality, etc.) were enrolled；
* Leptomeningeal metastasis after resistance to third-generation EGFR-TKIs;
* Histologically confirmed NSCLC LM patients by positive CSF cytology. The diagnosis of LM can be based on MRI with malignant cells in the cerebrospinal fluid, focal or diffuse enhancement of the leptomeninges, and enhancement of nerve roots or ependymal surfaces;
* no severe liver and kidney dysfunction;
* no other serious chronic diseases;
* Women should use adequate contraceptive methods throughout the study; Termination of pregnancy was recommended if pregnancy occurred during the study. Failure to heed the advice was at your own risk.
* Informed consent was signed.

Exclusion Criteria:

* Other patients except lung cancer were considered as malignant tumors;
* any unresolved pretreatment toxicity (except alopecia and grade 2 platinum-based neuropathy) greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the initiation of study treatment;
* Refractory nausea, vomiting, or chronic gastrointestinal disease, inability to swallow the study drug, or previous significant intestinal resection surgery, resulting in inadequate absorption of vormetinib;
* Patients with clinical manifestations of nervous system failure included severe encephalopathy, grade Ⅲ-Ⅳ white matter lesions confirmed by imaging examination, moderate or severe coma, and Glasgow coma scale less than 9;
* known history of hypersensitivity reactions to active or inactive excipients of vormetinib or drugs with a similar chemical structure or class to vormetinib;
* any of the following: pregnant women; Women who are lactating; Reluctance among men or women of childbearing potential to use appropriate contraception;
* previous history of myocardial infarction or other arterial thrombotic diseases (angina pectoris), symptomatic congestive heart failure (New York Heart Association grade ≥2), unstable angina pectoris or arrhythmia; Note: only allowed if the patient had no evidence of active disease for at least 6 months before randomization;
* History of cerebrovascular accident (CVA) or transient ischemic attack (TIA) ≤6 months before enrollment;
* history of hemorrhagic diathesis or coagulopathy;
* lack of adequate bone marrow reserve or organ function (enrollment at investigator's discretion) : absolute neutrophil count \<1.0×109/L; Platelet count \<75×109/L; Hemoglobin \<90 g/L; Alanine aminotransferase \> 2.5 times ULN; Aspartate aminotransferase \>2.5 times ULN; Total bilirubin \> 1.5 times ULN; Or liver metastasis patients AST and/or ALT \> 5× ULN, total bilirubin \>3×ULN; Serum creatinine \>1.5 times ULN and creatinine clearance \<50 mL/ minute (measured or calculated by the common formula of Cockcroft and Gault) International normalized ratio (INR)\> 1.5 and partial activated prothrombin time (APTT)\>1.5×ULN;
* major surgery within 28 days before the administration of the first dose of study drug (in China, major surgery was defined according to the "Administrative Measures for the Clinical Application of Medical Technology" which was implemented on May 1, 2009 and referred to grade 3 and 4 surgery);
* evidence of any severe or uncontrolled systemic illness, including uncontrolled hypertension, diabetes mellitus, and active bleeding, any nonadherence to the study or any active infection, including uncontrolled hepatitis B, hepatitis C, and human immunodeficiency virus (HIV), as considered by the investigator to be detrimental to patient participation or adherence to the protocol;
* For women of childbearing age, a negative urine or serum pregnancy test should be performed 3 days prior to receiving the first dose of study drug; Participants and their sexual partners were required to use a medically approved contraceptive method during the study treatment period and for 6 months after the end of the study treatment period. If a subject or a subject's partner becomes pregnant during the study, inform your study doctor immediately and the study doctor advises you or your partner to terminate the pregnancy; If you persist with the pregnancy, your doctor, with your consent, will continue to monitor the mother and baby until birth.

Where this trial is running

Nanjing, Jiangsu

• Nanjing Brain Hospital — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: fang S Cun

Conditions NSCLC