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

Plain English Summary

Pulsatile High-dose Furmonertinib in EGFR-mutant NSCLC With Leptomeningeal Metastasis is a Not Applicable clinical trial sponsored by Guangzhou University of Traditional Chinese Medicine studying NSCLC (Advanced Non-small Cell Lung Cancer), Leptomeningeal Metastasis, Furmonertinib, EGFR Activating Mutation. This trial tests if a higher, less frequent dose of furmonertinib is effective and safe for lung cancer that has spread to the brain's lining. It is for patients with advanced non-small cell lung cancer (NSCLC) that has a specific genetic mutation (EGFR) and has spread to the leptomeninges (the membranes surrounding the brain and spinal cord). Participants will receive either 320mg of furmonertinib every other day or 160mg daily, depending on their choice and doctor's recommendation, until their cancer progresses or side effects become unmanageable. Alternative treatments may include other targeted therapies or supportive care, depending on the patient's specific situation and previous treatments. The trial aims to enroll 42 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with advanced non-small cell lung cancer (NSCLC) with a confirmed EGFR mutation (exon 19 deletion or L858R). Patients must have leptomeningeal metastasis (cancer spread to the membranes around the brain and spinal cord) confirmed by spinal fluid tests and MRI. Must have progressed after initial treatment with a targeted therapy (TKI). Must be between 18 and 85 years old, with adequate organ function (blood counts, liver, and kidney function). This trial is studying NSCLC (Advanced Non-small Cell Lung Cancer), Leptomeningeal Metastasis, Furmonertinib, EGFR Activating Mutation, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how well the treatment controls cancer spread in the brain lining (leptomeningeal disease control rate), aiming to see if the new dosing schedule can stop or slow the canc The specific primary outcome measures are: LM-DCR (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.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial addresses a critical unmet need for patients with EGFR-mutant NSCLC that has spread to the brain lining, a challenging complication with limited effective treatment options. This research targets NSCLC (Advanced Non-small Cell Lung Cancer), Leptomeningeal Metastasis, Furmonertinib, EGFR Activating Mutation, where improved treatment options are needed.

Investor Insight

This trial targets a specific patient population with a difficult-to-treat complication of lung cancer, potentially offering a new therapeutic option if successful, which could lead to significant mar

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of each treatment arm (320mg every other day vs. 160mg daily). Understand how often you will need to come in for assessments, including imaging scans and blood tests. Be prepared for potential side effects and discuss how they will be managed. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 42 participants

Interventions

• DRUG: Furmonertinib 320mg qod po — furmonertinib 320mg qod po until disease, progression or uncontrollable adverse reactions occur.
• DRUG: Furmonertinib 160mg qd po — furmonertinib 160mg qd po until disease, progression or uncontrollable adverse reactions occur.

Primary Outcomes

• LM-DCR (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

• 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.)

Full 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).

Trial Locations

• Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer (NSCLC)
• Leptomeningeal Metastasis
• EGFR Mutations
• Tyrosine Kinase Inhibitors (TKIs)
• Targeted Therapy
• Oncology
• Brain Metastasis
• Lung Cancer Complications
• Chemotherapy
• Cancer Treatment Resistance

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