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High-Dose Firmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed in the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer With Leptomeningeal Metastasis | Clinical Trials | Clareo Health

NOT_YET_RECRUITINGPHASE2

High-Dose Firmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed in the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer With Leptomeningeal Metastasis

A Multicenter, Prospective Phase II Clinical Study of High-Dose Firmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed in the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer With Leptomeningeal Metastasis

NCT06971406•Qiming Wang

View on ClinicalTrials.gov

Summary

Primary Objective: To evaluate the efficacy of high-dose firmonertinib combined with bevacizumab and intrathecal pemetrexed in EGFR Ex19del/L858R-mutated non-small cell lung cancer (NSCLC) with leptomeningeal metastasis (LM), as measured by Overall Survival (OS). Secondary Objectives: 1. To assess the efficacy of this regimen in EGFR Ex20ins/PACC/L861Q-mutated NSCLC with LM. 2. To further evaluate therapeutic outcomes across cohorts, including: * Time to Treatment Failure (TTF) * Leptomeningeal Objective Response Rate (ORR-LM) * Clinical Response Rate 3. To analyze the impact of this regimen on \*quality of life\* using standardized metrics: * EORTC QLQ-C30 * EORTC QLQ-LC13 4. To assess safety profiles across cohorts, focusing on: * Incidence and severity of adverse events (AEs) graded per \*CTCAE v5.0\* * Frequency of treatment-related toxicities Exploratory Objectives: To investigate correlations between dynamic changes in: * Plasma-derived circulating tumor DNA (ctDNA) * Cerebrospinal fluid-derived cell-free DNA (cfDNA) and clinical outcomes through comparative analysis of genomic profiling and epigenetic signatures before and after treatment.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Have obtained written informed consent from the patient or his or her legal representative.
•2. Age ≥18 years, male or female.
•3. Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC).
•4. EGFR mutations confirmed by genetic testing (EGFR Ex19del/L858R/Ex20ins/PACC/L861Q).
•5. Leptomeningeal metastasis diagnosed by comprehensive clinical assessment according to "EANO-ESMO" diagnostic criteria, including symptom evaluation, imaging assessment, and/or cerebrospinal fluid (CSF) cytopathological evaluation.
•6. Both treatment-naïve leptomeningeal metastasis patients and those who progressed after standard antitumor therapies in clinical practice are eligible. ≤3 prior lines of therapy allowed (patients with \>3 prior lines may enroll in the real-world study cohort).
•7. ECOG PS 0-2 (patients with ECOG PS \>2 may enroll in the real-world study cohort).
•8. Prior radiotherapy or surgical treatment targeting the central nervous system (CNS) is permitted.
•9. Patients with CNS symptoms/signs are allowed if these manifestations are not life-threatening.
•10. Patients previously treated with standard-dose third-generation EGFR TKIs, pemetrexed intravenous infusion, or bevacizumab are permitted.
+3 more criteria

Exclusion Criteria

•1. Diagnosis of other malignancies within the past 5 years or history of other malignancies (except adequately controlled basal cell carcinoma of the skin, cervical carcinoma in situ, or ductal carcinoma in situ of the breast).
•2. Severe gastrointestinal disorders affecting drug administration or absorption, including but not limited to peptic ulcer disease, inflammatory bowel disease, etc.
•3. Known or suspected hypersensitivity to the investigational drugs (Firmonertinib, Bevacizumab, Pemetrexed) or any of their excipients.
•4. Prior treatment with high-dose third-generation EGFR TKI or intrathecal chemotherapy with Pemetrexed.
•5. Evidence of any severe or uncontrolled systemic diseases, including uncontrolled hypertension, diabetes, active bleeding, or active infections (e.g., hepatitis B/C, HIV), which in the investigator's judgment may jeopardize patient participation or protocol compliance.
•6. History of steroid-requiring radiation pneumonitis or any evidence of active interstitial lung disease.
•7. Clinically significant cardiac arrhythmias (e.g., QTc interval \>500 ms) or heart failure (left ventricular ejection fraction \<50%).
•8. Pregnant or lactating women.
•9. Patients currently participating in or having received investigational drug therapy within 2 weeks prior to enrollment.
•10. Other severe acute/chronic medical or psychiatric conditions or laboratory abnormalities that, in the investigator's opinion, may increase study-related risks, interfere with result interpretation, or compromise the patient's ability to complete the study or adhere to protocol requirements.

Key Dates

Start Date

May 15, 2025

Primary Completion Date

January 1, 2027

Completion Date

June 1, 2027

Last Updated

May 14, 2025

Enrollment

100

ESTIMATED participants

Conditions

Non Small Cell Lung CancerEGFR MutationLeptomeningeal MetastasesTargeted Therapy

Interventions

Combination therapy prospective cohort

DRUG

Contacts

Haiyang Chen

CONTACT

+86 15003879297 chenocean017@126.com

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 14, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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High-Dose Firmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed in the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer With Leptomeningeal Metastasis

Inclusion Criteria

Exclusion Criteria

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