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

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