Pulsatile high-dose furmonertinib for EGFR-mutant NSCLC with leptomeningeal metastasis
Pulsatile High-dose Furmonertinib in EGFR-mutant NSCLC With Leptomeningeal Metastasis
This tests whether taking high-dose furmonertinib every other day helps people with EGFR-mutant non-small cell lung cancer that has spread to the leptomeninges.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 42 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Guangzhou University of Traditional Chinese Medicine Academic / other |
| Drugs / interventions | furmonertinib |
| Locations | 1 site (Guangzhou, Guangdong) |
| Trial ID | NCT07348965 on ClinicalTrials.gov |
What this trial studies
This interventional study compares a pulsatile high-dose schedule of furmonertinib (320 mg every other day) with the standard 160 mg daily dosing in patients with EGFR exon 19 deletion or exon 21 L858R NSCLC and cerebrospinal fluid (CSF)-confirmed leptomeningeal metastasis. The trial will measure clinical efficacy and safety, and collect pharmacokinetic data including CSF concentrations and CSF penetration rates. It will also perform genomic analyses to explore how co-occurring mutations influence response and prognosis. Patients must have progressed after first-line TKI therapy and meet predefined organ function criteria.
Who should consider this trial
Good fit: Adults aged 18–85 with histologically confirmed NSCLC harboring EGFR exon 19 deletion or exon 21 L858R, CSF-cytology–positive leptomeningeal metastasis, progression after first-line TKI, and adequate organ function are eligible.
Not a fit: Patients without EGFR activating mutations, without CSF-confirmed leptomeningeal disease, with poor organ function, or with resistance mutations not overcome by furmonertinib are unlikely to benefit.
Why it matters
Potential benefit: If successful, this approach could raise drug levels in the CSF and improve neurological disease control and clinical outcomes for patients with leptomeningeal spread.
How similar studies have performed: Prior work with higher or pulsatile dosing of EGFR TKIs (notably osimertinib) has shown improved CSF penetration and some clinical activity, but high-dose pulsatile furmonertinib is less well studied.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Patients with non-small cell lung cancer (NSCLC) confirmed by histopathological or cytopathological examination 2. Patients with EGFR exon 19 deletion or exon 21 L858R mutation 3. Patients with leptomeningeal metastasis (LMD) confirmed by positive cerebrospinal fluid (CSF) cytology (within 28 days prior to the first dose administration) and with at least 1 LMD lesion that can be repeatedly evaluated by magnetic resonance imaging (MRI) 4. Patients with disease progression after first-line tyrosine kinase inhibitor (TKI) treatment 5. Aged ≥18 years and ≤85 years, with no gender restrictions. 6. Sufficient organ function, defined as: absolute neutrophil count ≥ 1.5×10⁹/L, platelet count ≥ 75×10⁹/L, hemoglobin ≥ 90g/L total bilirubin ≤ 1.5×upper limit of normal (ULN) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN (for patients with liver metastasis, total bilirubin can be relaxed to ≤ 3×ULN, and ALT/AST can be relaxed to ≤ 5×ULN) serum creatinine ≤ 1.5×ULN or creatinine clearance ≥ 50 mL/min (calculated by the Cockcroft-Gault formula) 7. For patients enrolled in the pharmacokinetic study: no prior treatment with furmonertinib (either in combination or as monotherapy) 8. Patients who have signed the informed consent form, are willing to receive treatment under this protocol, can adhere to medication administration, and have good compliance. Exclusion Criteria: 1. Unable to complete the baseline assessment form 2. Complicated with severe or uncontrolled systemic diseases, including active infection, electrolyte disturbance, bleeding tendency, etc. 3. Pregnant or lactating women, or those with planned pregnancy during the study or within 6 months after the study ends 4. Presence of central nervous system complications requiring emergency neurosurgical intervention 5. Suffering from other malignant tumors or having a history of other malignant tumors 6. Complicated with severe brain diseases or mental illnesses that affect the patient's ability to report symptoms by themselves 7. Individuals without legal capacity, or those for whom medical or ethical reasons affect the continuation of the study 8. Other circumstances deemed unsuitable for participation in this study by the researcher. 9. Patients with a severe allergic diathesis, especially those who have experienced severe drug allergies or other serious adverse reactions during previous treatment with tyrosine kinase inhibitors (TKIs).
Where this trial is running
Guangzhou, Guangdong
- Guangdong Provincial Hospital of Chinese Medicine — Guangzhou, Guangdong, China (Recruiting)
Study contacts
- Principal investigator: Haibo Zhang, M.D. — Guangdong Provincial Hospital of Traditional Chinese Medicine
- Study coordinator: Yanjuan Zhu, M.D.
- Email: zyjsophy@gzucm.edu.cn
- Phone: 86-20-81887233
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.