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

NCT07348965 | Recruiting

• 1 other identifier: ZF2025-387-01
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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

Keywords

NSCLC; furmonertinib; leptomeningeal metastasis; cerebrospinal fluid

Outcome Measures

Primary Outcomes (1)

• LM-DCR

  Leptomeningeal metastasis-disease control rate, calculated as the proportion of patients with leptomeningeal metastasis who achieve remission or stable disease, which will be determined based on the modified imaging assessment method formulated by the RANO-LM working group with imaging assessments.

  From date of first administration of the study drug until the date of first documented leptomeningeal disease progression or date of death from any cause, whichever came first, assessed up to 3 years.

Secondary Outcomes (11)

• LM-ORR

  From date of first administration of the study drug until the date of first documented leptomeningeal disease progression or date of death from any cause, whichever came first, assessed up to 3 years.

• neurological function

  From date of first administration of the study drug until the date of first documented leptomeningeal disease progression or date of death from any cause, whichever came first, assessed up to 3 years.

• iDoR

  From date of first administration of the study drug until the date of first documented leptomeningeal disease progression or date of death from any cause, whichever came first, assessed up to 3 years.

• iPFS

  From date of enrollment until the date of first documented leptomeningeal disease progression or date of death from any cause, whichever came first, assessed up to 3 years.

• PFS

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.

Study Arms (2)

Cohort A

EXPERIMENTAL

furmonertinib 320mg qod po

Drug: Furmonertinib 320mg qod po

Cohort B

OTHER

furmonertinib 160mg qd po

Drug: Furmonertinib 160mg qd po

Interventions

Furmonertinib 320mg qod po DRUG

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

Cohort A

Furmonertinib 160mg qd po DRUG

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

Cohort B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with non-small cell lung cancer (NSCLC) confirmed by histopathological or cytopathological examination
• Patients with EGFR exon 19 deletion or exon 21 L858R mutation
• 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)
• Patients with disease progression after first-line tyrosine kinase inhibitor (TKI) treatment
• Aged ≥18 years and ≤85 years, with no gender restrictions.
• 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)
• For patients enrolled in the pharmacokinetic study: no prior treatment with furmonertinib (either in combination or as monotherapy)
• 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.

You may not qualify if:

• Unable to complete the baseline assessment form
• Complicated with severe or uncontrolled systemic diseases, including active infection, electrolyte disturbance, bleeding tendency, etc.
• Pregnant or lactating women, or those with planned pregnancy during the study or within 6 months after the study ends
• Presence of central nervous system complications requiring emergency neurosurgical intervention
• Suffering from other malignant tumors or having a history of other malignant tumors
• Complicated with severe brain diseases or mental illnesses that affect the patient's ability to report symptoms by themselves
• Individuals without legal capacity, or those for whom medical or ethical reasons affect the continuation of the study
• Other circumstances deemed unsuitable for participation in this study by the researcher.
• 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).

Sponsors & Collaborators

• Guangzhou University of Traditional Chinese Medicine: lead

Study Sites (1)

Guangdong Provincial Hospital of Chinese Medicine

Guangzhou, Guangdong, 510120, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis

Interventions

aflutinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases

Study Officials

• Haibo Zhang, M.D.

  Guangdong Provincial Hospital of Traditional Chinese Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanjuan Zhu, M.D.

CONTACT

86-20-81887233; zyjsophy@gzucm.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2025
• First Posted: January 16, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)