NCT06971406

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

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Qiming Wang · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Non Small Cell Lung Cancer
• EGFR Mutation
• Leptomeningeal Metastases
• Targeted Therapy

Interventions

Type	Name	Description
DRUG	Combination therapy prospective cohort	high-dose firmonertinib (240 mg, daily), bevacizumab (15 mg/kg, every 3 weeks), and pemetrexed (50 mg, intrathecal chemotherapy C1d1d5, then every 3 weeks)

Timeline

• Start date: 2025-05-15
• Primary completion: 2027-01-01
• Completion: 2027-06-01
• First posted: 2025-05-14
• Last updated: 2025-05-14