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.
Have obtained written informed consent from the patient or his or her legal representative.
Age ≥18 years, male or female.
Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC).
EGFR mutations confirmed by genetic testing (EGFR Ex19del/L858R/Ex20ins/PACC/L861Q).
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).
Severe gastrointestinal disorders affecting drug administration or absorption, including but not limited to peptic ulcer disease, inflammatory bowel disease, etc.
Known or suspected hypersensitivity to the investigational drugs (Firmonertinib, Bevacizumab, Pemetrexed) or any of their excipients.
Prior treatment with high-dose third-generation EGFR TKI or intrathecal chemotherapy with Pemetrexed.
Qiming Wang
Lead sponsor
Henan Cancer Hospital
Sponsor institution