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.

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

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.

Available from June 2029 (after completion of primary analysis) to December 2034 (5 years after data availability).

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.