Furmonertinib 160mg vs 80mg + Chemotherapy in EGFR-Mutated NSCLC With Brain Metastases: Efficacy and Safety Study

Furmonertinib 160mg Versus Furmonertinib 80mg Combined With Chemotherapy (Carboplatin + Pemetrexed) as First-Line Treatment for EGFR-Mutated NSCLC Patients With Brain Metastases: A Multicenter Study of Efficacy and Safety

This multicenter study evaluates the efficacy and safety of furmonertinib 160mg versus furmonertinib 80mg plus chemotherapy (carboplatin + pemetrexed) as first-line treatment for EGFR-mutated NSCLC patients with brain metastases. It aims to determine which approach is more effective and safer.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-small Cell Lung Cancer (NSCLC); Brain Metastases; EGFR Mutation; Furmonertinib
• Intervention / Treatment: Drug: Furmonertinib; Drug: Furmonertinib; Drug: carboplatin; Drug: pemetrexed

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dingzhi Huang Huang; Phone Number: +86-22-23340123-1031; Email: dingzhih72@163.com

Study Locations

• China
  • Tianjin, China
    • Tianjin Medical University Cancer Institute and Hospital
    • Contact: Dingzhi Huang Huang; Phone Number: +86-22-23340123-1031; Email: dingzhih72@163.com

Participation Criteria

Eligibility Criteria

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

Description

IInclusion Criteria

• Aged 18 to 75 years (male or female)
• Histopathologically confirmed, unresectable, and non-radiocurable newly -diagnosed locally advanced or metastatic lung adenocarcinoma
• Confirmed by local laboratory to have one of the following EGFR mutations: -19Del or L858R (single or mixed mutations are allowed)
• Treatment-naive for locally advanced (not suitable for surgery/radiotherapy per investigator) or metastatic NSCLC; adjuvant/neoadjuvant therapy completed >6 months before first progression is allowed (≤6 months is considered pretreated)
• At least one measurable tumor lesion per RECIST 1.1 (lesions previously treated with radiotherapy are excluded; if only one measurable lesion exists, biopsy is allowed but baseline imaging must be performed ≥14 days after biopsy)
• Confirmed stable and asymptomatic brain metastases
• Sufficient organ function (per laboratory tests): ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L, HGB ≥90g/L; TBIL ≤1.5×ULN, AST/ALT ≤2.5×ULN (for liver metastasis: TBIL ≤3×ULN, AST/ALT ≤5×ULN); CrCL ≥50 ml/min (Cockcroft-Gault formula)
• ECOG performance status 0-2 (no significant disease deterioration in 2 weeks before screening)
• Expected survival >12 weeks after first dose
• Non-pregnant women of childbearing potential (no pregnancy plan); women and men agree to use effective contraception during the study and 6 months after drug discontinuation
• Voluntarily signs informed consent and understands the study procedures Exclusion Criteria（排除标准）
• NSCLC with predominantly squamous cell histology, small cell lung cancer, neuroendocrine carcinoma, or other non-adenocarcinoma histologies
• Concurrent positive for other driver genes (ALK fusion, ROS1 fusion, RET rearrangement, BRAF mutation, NTRK fusion, MET mutation, KRAS mutation); TP53, RB1, and BRAC mutations are excluded
• Expected to receive other anti-tumor therapies during the trial
• Major surgery (except vascular access or biopsy) within 4 weeks before first dose or planned during the trial
• Use of CYP3A4 strong inhibitor within 7 days or strong inducer within 21 days before first dose; use of anti-tumor Chinese medicine within 2 weeks before first dose or planned during the trial
• Participation in other clinical trials (investigational drug/device) within 4 weeks or 5 half-lives before first dose
• Use of other anti-tumor drugs within 14 days before first dose
• Spinal cord compression or symptomatic leptomeningeal metastasis
• Toxicity from previous anti-tumor therapy not recovered to ≤CTCAE Grade 1 (except alopecia or platinum-induced peripheral neuropathy)
• Symptomatic or unstable pleural/peritoneal effusion (stable ≥14 days after drainage is allowed)
• History of other malignancies (except cured malignancies with no recurrence in 5 years: cervical carcinoma in situ, basal cell carcinoma, papillary thyroid carcinoma)
• History of interstitial lung disease (ILD), drug-induced ILD, steroid-requiring radiation pneumonitis, or suspected ILD
• Uncontrolled severe systemic diseases (e.g., hypertension, diabetes, NYHA III-IV heart failure, unstable angina, myocardial infarction within 1 year, active bleeding)
• QTc >470 msec on resting ECG
• Clinically significant QT prolongation or arrhythmias increasing QT risk (e.g., complete left bundle branch block, III° AV block, congenital long QT syndrome, severe hypokalemia, use of drugs causing QT prolongation)
• Severe gastrointestinal dysfunction that impairs drug intake or absorption Infections requiring intravenous medication
• Active mental illness or drug addiction
• Known or suspected allergy to furmonertinib or its components
• Pregnant or lactating women; women or their partners planning pregnancy during the study
• Poor compliance (unable to follow study procedures)
• Other conditions deemed unsuitable for enrollment by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Furmonertinib 160mg Group; Participants receive oral furmonertinib 160mg once daily as first-line treatment.	Drug: Furmonertinib; Oral administration, 160mg once daily.; Drug: Furmonertinib; Oral administration, 80mg once daily
Active Comparator: Furmonertinib 80mg + Chemotherapy Group; Participants receive oral furmonertinib 80mg once daily combined with intravenous carboplatin + pemetrexed (cycle-based) as first-line treatment.	Drug: Furmonertinib; Oral administration, 160mg once daily.; Drug: Furmonertinib; Oral administration, 80mg once daily; Drug: carboplatin; Intravenous infusion, cycle-based (per study protocol).; Drug: pemetrexed; Intravenous infusion, cycle-based (per study protocol).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-Free Survival (PFS) as assessed by Investigator	The time from the first dose of the study drug to the progression of the disease (Investigator-Assessed) or death for any reason according to investigator.	Approximately 18 months after the first patient begin study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) as assessed by RECIST 1.1	Proportion of subjects whose tumors were assessed as complete response(CR) or partial response(PR) according to RECIST 1.1.	Approximately 12 weeks following the first dose of study drug
Disease Control Rate (DCR) as assessed by RECIST 1.1	Proportion of subjects whose tumors were assessed as CR, PR or stable disease (SD) according to RECIST 1.1.	Approximately 18 months from the first patient begin study treatment
Central Nervous System (CNS) Objective Response Rate (CNS ORR) as assessed by RECIST 1.1	Proportion of subjects whose central nervous system (CNS) tumors (including intracranial parenchymal metastases and asymptomatic meningeal metastases as defined in the inclusion criteria) are assessed as Complete Response (CR) or Partial Response (PR) according to RECIST1.1.	Approximately 12 weeks after the first dose of study drug
Central Nervous System (CNS) Disease Control Rate (CNS DCR) as assessed by RECIST 1.1	Proportion of subjects whose central nervous system (CNS) tumors (including intracranial parenchymal metastases and asymptomatic meningeal metastases as defined in the inclusion criteria) are assessed as Complete Response (CR), Partial Response (PR), or Stable Disease (SD) according to RECIST 1.1.	Approximately 18 months after the first dose of study drug
Central Nervous System Progression-Free Survival (CNS PFS) as assessed by RECIST 1.1	The time from the first dose of the study drug (Furmonertinib) to the first occurrence of central nervous system (CNS) disease progression (assessed by RECIST 1.1) or death from any cause, whichever comes first.	Approximately 18 months after the first dose of study drug
Median Overall Survival (OS)	The time from the first does of the study drugs to the death for any reason	Approximately 24 months after the first dose of study drug
Safety Profile (Adverse Events, AE) as assessed by CTCAE v5.0	The number of patients with adverse events and the severity grading (Grade 1-5) according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.	From the start of study drug to 28 days after the last dose of study drug
Progression Pattern as assessed by RECIST 1.1 and Clinical Evaluation	Proportion of subjects with first disease progression classified as Intracranial, extracranial, or combined intracranial-extracranial progression.	Approximately 18 months after the first dose of study drug
Site Analysis of Disease Progression as assessed by RECIST 1.1 and Clinical Evaluation	Frequency of specific progression sites.	Approximately 18 months after the first dose of study drug

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 26, 2025
• First Submitted That Met QC Criteria: January 23, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 23, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Nervous System Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Pemetrexed; Carboplatin; aflutinib
• Other Study ID Numbers: E20250722

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) to be shared include demographic characteristics, clinical baseline data (e.g., ECOG PS score, EGFR mutation status, brain metastasis status), efficacy endpoints (median PFS, ORR, DCR, CNS ORR, CNS DCR, CNS PFS, OS) assessed by RECIST 1.1, adverse event data graded by CTCAE v5.0, progression pattern and site data, and biomarker (NGS) data collected at baseline and disease progression. The data will be made available after the completion of the primary analysis (expected by December 2028) for non-commercial scientific research purposes, to support further exploration of EGFR-mutated NSCLC with brain metastasis treatment.
• IPD Sharing Time Frame: Available from June 2029 (after completion of primary analysis) to December 2034 (5 years after data availability).
• IPD Sharing Access Criteria: Researchers interested in accessing the IPD must submit a formal research proposal to the leading research unit (Tianjin Medical University Cancer Institute and Hospital) and the sponsor for review. Approval will be granted based on the scientific merit of the proposal, alignment with the study's objectives, and compliance with data privacy and ethical requirements. A data use agreement (DUA) must be signed prior to data access, prohibiting re-identification of participants and restricting data use to non-commercial research.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No