High-dose Furmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed Chemotherapy in Patients With EGFR-mutated Non-small Cell Lung Cancer and Meningeal Metastasis

A Single-arm, Multicenter, Phase 2 Study of High-dose Furmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed Chemotherapy in Patients With EGFR-mutated Non-small Cell Lung Cancer and Meningeal Metastasis

the study conducted to evaluate the efficacy and safety of high-dose furmonertinib (160 mg qd) combined with bevacizumab and pemetrexed intrathecal chemotherapy in NSCLC patients with EGFR mutations and meningeal metastases.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer Metastatic
• Intervention / Treatment: Drug: furmonertinib

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological or cytological localization is NSCLC;
• confirmed EGFR exon 19 deletion mutation(19del) or EGFR exon 21L858R mutation (L858R) or EGFR exon 20 T790M mutation (T790M)）;
• Clinical diagnosis of meningeal aggravation: clinical symptoms of intracranial hypertension (headache, dizziness, vomiting, etc.) + imaging confirmation (cerebral MRI diagnosis of meningeal aggravation) or cerebrospinal fluid cytology confirmation;
• for patients with symptoms who are considered to need temporary brain local. Treatment of cough receiving adrenal corticosteroids must be kept stable or reponse for at least 1 week before the first trial of the drug preparation;
• Newly diagnosed meningeal metastasis, including meningeal metastasis after previous brain surgery and/or local radiotherapy for solid metastatic disease;
• Patients did not received systemic treatment after diagnosed meningeal metastases.
• Obtain informed consent signed by the patient's legal representative;
• Aged ≥18 years and ≤75 years;
• Eastern Tourism Cooperation Group (ECOG) Physical condition evaluation 0-1;
• Life expectancy ≥12 week;
• Able to follow the requirements of the study protocol and confirmation procedures, and able to accept cranial wall medications;
• contraception.

Exclusion Criteria:

• Mixed non-small cell and small cell carcinoma, or squamous cell carcinoma as the main pathological type;
• history of hypersensitivity reaction to active or inactive excipients of furmonertinib, bevacizumab or pemetrexed or to drugs of similar structure or class to the investigational drug;
• Currently participating in an interventional clinical trial, or having received other study drugs or study devices within 4 weeks before the first study drug;
• Patients who have received solid organ or blood system transplantation;
• Patients with severe intracranial hypertension symptoms that cannot be relieved by discontinuation of dexamethasone and/or glycol treatment, or patients in intensive care;
• Ensure control of the patient's symptomatic pericardial, peritoneal, and pleural effusions;
• History of cancer in the last five years Other malignancies or a history of other malignancies;
• Recent active digestive events, such as duodenitis, ileitis, intestinal perforation, intestinal catheters, or other conditions that may cause gastrointestinal tract or perforation; or refractory vomiting, chronic gastrointestinal disease, inability to swallow study drugs, or previous colorectal cancer resection that prevents adequate drug absorption;
• The patient has a physique that is prone to Japanese language learning or has active Japanese language learning; Central squamous cell carcinoma or Patients at greater risk for hemoptysis; Any diamond event ≥ CTCAE grade 3, presence of open wounds, injuries or fractures in the 28th century before the first creation; if in the first Asthma was accepted 28 days before the organization meeting, the wound treatment should be evaluated by the interval period;
• History of arterial thromboembolism within the last 6 months, including vascular cerebral accident, myocardial infarction, transient cerebral contemplation;
• History of grade 4 venous thrombosis within the last 6 months, including fire embolism;
• The presence of any severe or uncontrolled systemic evidence, including difficult-to-control hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg), uncontrolled diabetes, etc.;
• Active infections include, for example, hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) infections (including those requiring intravenous therapy, active hepatitis B infection includes patients with positive hepatitis B surface test based on serological assessment and hepatitis B virus DNA >1000 copies/ml);
• previous history of interstitial lung disease, drug-induced interstitial lung disease, pneumonitis requiring steroid therapy, or any evidence of active interstitial lung disease;

• The first 28-day inspection of the drug preparation showed Lack of adequate bone marrow reserve or organ function （Within 2 weeks before blood test, No blood transfusion or blood products, granulocyte colony-stimulating factor or other hematopoietic stimulating factors were used for repair）:

  • Absolute neutrophil count <1.5 × 109/L; continuous count <100×109/L; hemoglobin <90 g/L;
  • Alanine aminotransferase > 2.5 times Upper limit of normal value (Upper limit of normal）; Aspartate aminotransferase>2.5 times ULN; Total bilirubin>1.5 times ULN; or liver transplant patients with AST and/or ALT > 5× ULN;
  • Albumin <30 g/L;
  • Serum creatinine >1.5 times ULN, and Creatinine clearance <50 mL/min （Measured or calculated by Cockcroft and Gault formula);
  • International normalized ratio (INR) > 1.5,Partially activated zymogen time （APTT>1.5 times Upper limit of normal;
  • Urine protein ≥++, and 24-hour protein >2.0g;

• Any of the following Bishop criteria:

  • Clinically significant resting electrocardiogram rhythm, respiratory, or morphological abnormalities, such as left bundle branch block, third-degree myocardial insufficiency, and second-degree myocardial insufficiency, within 28 days before the first study drug perfume;
  • Possibility Interphase Factors that increase the risk of prolonged or arrhythmic events, such as heart failure, congenital long Quantum Dots Syndrome, long Quantum Dots Family history or first-degree relatives 40 Sudden death due to coma or known prolonged Quantum Dots Any sudden or difficult to fully compensate low potassium tariffs, low tariff tariffs, and low tariff-to-tariff tariffs during the period;
  • Left ventricular ejection fraction (LVEF)Left ventricular ejection fraction）<50%, recent History of myocardial infarction, severe or unstable angina, or coronary artery bypass grafting within the past month or heart failure≥ New York Heart Association (New York Heart Association (NYHA) 2 class;
• Pregnancy or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Furmonertinib combined with bevacizumab and intrathecal pemetrexed chemotherapy; patients receive furmonertinib (160mg, once a day) combined with bevacizumab (7.5 mg/kg, once every 3 weeks) and pemetrexed (50 mg intrathecal injection chemotherapy, once every 3 weeks).	Drug: furmonertinib; furmonertinib (160mg, once a day, continuous administration); bevacizumab (7.5 mg/kg body weight, once every 3 weeks); Pemetrexed (50 mg intrathecal injection chemotherapy, once every 3 weeks).; Other Names: bevacizumab; pemetrexed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial progression-free survival	The time from receipt of study treatment to intracranial tumor PD or to death due to any cause,whichever came first,	The time from receipt of study treatment to intracranial tumor PD or to death due to any cause,whichever came first, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
systemic progression-free survival	The time from receipt of study treatment to systemic PD or to death due to any cause,whichever came first,	The time from receipt of study treatment to systemic PD or to death due to any cause,whichever came first, assessed up to 24 months.
intracranial objective response rate	The number and percentage of objective response (PR+CR) of intracranial tumor at each time point after treatment	The number and percentage of objective response (PR+CR) of intracranial tumor at each time point after treatment, through study completion, an average of 12 months.
overall survival	The time interval between enrollment and death from any cause	The time interval between enrollment and death from any cause,,whichever came first, assessed up to 24 months.
safety and tolerability	adverse events will be reported and graded according to the National Cancer Institute (NCI) CTCAE version 5.0.	adverse events will be reported and graded according to the National Cancer Institute (NCI) CTCAE version 5.0.,assessed up to 24 months.

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Actual): October 20, 2025
• Study Completion (Actual): March 30, 2026

Study Registration Dates

• First Submitted: February 2, 2025
• First Submitted That Met QC Criteria: February 2, 2025
• First Posted (Actual): February 6, 2025

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: EGFR mutated; meningeal metastasis
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Meningeal Neoplasms; Central Nervous System Neoplasms; Meningeal Carcinomatosis; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Bevacizumab; Pemetrexed; aflutinib
• Other Study ID Numbers: GASTO 10120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No