Pulsatile High-dose Furmonertinib in EGFR-mutant NSCLC With Leptomeningeal Metastasis

NCT ID: NCT07348965

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2028-12-31

Brief Summary

The goal of this clinical trial is to clarify the efficacy and safety of the high-dose alternate-day furmonertinib in NSCLC with leptomeningeal metastasis. It will also explore the mechanism by which the high-dose alternate-day administration regimen enhances efficacy from a pharmacokinetic perspective, and investigate the impact of co-occurring mutations on the efficacy and prognosis of furmonertinib in the treatment of EGFR-mutant NSCLC with leptomeningeal metastasis. The main questions it aims to answer are:

Does the high-dose alternate-day administration regimen have definite efficacy? Does the high-dose alternate-day administration regimen have favorable safety? Does the high-dose alternate-day administration regimen improve efficacy by increasing the cerebrospinal fluid (CSF) concentration and CSF penetration rate of the drug? Which co-occurring mutations may affect the efficacy and prognosis of patients with EGFR-mutant NSCLC and leptomeningeal metastasis? Participants will enter Cohort A (320mg qod po) or Cohort B (160mg qd po) to receive furmonertinib based on their own willingness and the clinician's decision, until disease, progression or uncontrollable adverse reactions occur. All patients in Cohort A will undergo efficacy and safety evaluation, with some also participating in pharmacokinetic study; patients in Cohort B will only undergo pharmacokinetic study.

Efficacy and safety evaluation will be conducted through imaging examinations, neurological function assessment scales, quality of life self-assessment scales, and adverse event records. Pharmacokinetic study will be carried out by detecting the plasma concentrations and CSF concentrations of furmonertinib and its active metabolites, and calculating the CSF penetration rate for evaluation.

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer); Leptomeningeal Metastasis; Furmonertinib; EGFR Activating Mutation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A

furmonertinib 320mg qod po

Group Type: EXPERIMENTAL

Furmonertinib 320mg qod po

Intervention Type: DRUG

furmonertinib 320mg qod po until disease, progression or uncontrollable adverse reactions occur.

Cohort B

furmonertinib 160mg qd po

Group Type: OTHER

Furmonertinib 160mg qd po

Intervention Type: DRUG

furmonertinib 160mg qd po until disease, progression or uncontrollable adverse reactions occur.

Interventions

Furmonertinib 320mg qod po

furmonertinib 320mg qod po until disease, progression or uncontrollable adverse reactions occur.

Intervention Type: DRUG

Furmonertinib 160mg qd po

furmonertinib 160mg qd po until disease, progression or uncontrollable adverse reactions occur.

Intervention Type: DRUG

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangzhou University of Traditional Chinese Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Haibo Zhang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Guangdong Provincial Hospital of Traditional Chinese Medicine

Locations

Guangdong Provincial Hospital of Chinese Medicine

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Yanjuan Zhu, M.D.

Role: CONTACT

zyjsophy@gzucm.edu.cn

86-20-81887233 ext. 34830

Facility Contacts

Yanjuan Zhu, M.D.

Role: primary

zyjsophy@gzucm.edu.cn

86-20-81887233 ext. 34830

Other Identifiers

ZF2025-387-01

Identifier Type: -

Identifier Source: org_study_id