Comparing firmonertinib to chemotherapy for advanced lung cancer with specific mutations

Inclusion Criteria:

1. Voluntarily sign the informed consent form (ICF).
2. Age ≥18 years at the time of ICF signing.
3. At least one measurable lesion per RECIST v1.1, meeting the following:

   * No prior local therapy (e.g., radiotherapy)
   * Not used for biopsy during screening
4. Histologically/cytologically confirmed non-squamous NSCLC, classified as:

   * Locally advanced (Stage IIIB/IIIC, unsuitable for curative surgery and/or definitive chemoradiotherapy)
   * Metastatic (Stage IV) (Based on UICC/AJCC 8th edition TNM staging)
5. Agreement to provide:

   * Recent tumor tissue (from untreated lesions)
   * Blood samples
   * Central lab-confirmed EGFR PACC or L861Q mutation (If tumor tissue is unavailable due to inaccessible lesions, sponsor consultation is required.)
6. No prior systemic therapy for advanced/metastatic NSCLC.

   * Allowed if: Prior (neo)adjuvant/definitive chemoradiotherapy completed ≥12 months before recurrence/progression
7. ECOG performance status 0-1.
8. Life expectancy ≥12 weeks.
9. Adequate bone marrow/organ function within 14 days before treatment (no transfusion/G-CSF within 2 weeks prior).
10. Women of childbearing potential (WOCBP):

    * Abstinence or contraception use
    * No egg donation
11. Non-sterilized males:

    * Abstinence or contraception use
    * No sperm donation
12. CNS metastases allowed if protocol-specified criteria are met.

Exclusion Criteria:

1. Histologically/cytologically confirmed tumor with \>10% neuroendocrine carcinoma, sarcomatoid carcinoma, or squamous cell components.
2. Known ALK-positive, ROS1-positive, RET fusion-positive, NTRK fusion-positive, BRAF V600E mutation, MET exon 14 skipping mutation, or other targetable alterations with approved therapies.
3. Prior treatments including:

   1. Systemic anti-tumor therapy for advanced/metastatic NSCLC (e.g., chemotherapy/targeted/immunotherapy). Neoadjuvant/adjuvant therapy exceptions per Inclusion Criterion #6.
   2. \>30 Gy thoracic radiotherapy within 6 months or non-thoracic radiotherapy within 4 weeks prior to first dose (brain radiotherapy exceptions per Inclusion Criterion #12).
   3. Any prior EGFR-targeted therapy (including investigational EGFR-TKIs, mAbs, bispecific antibodies, etc.).
   4. Strong CYP3A4 inhibitors within 7 days or inducers within 21 days prior to first dose.
   5. Anticancer traditional Chinese medicines within 2 weeks prior to first dose.
   6. Non-specific immunomodulators (e.g., interferon, IL-2, thymosin) within 2 weeks prior to first dose.
   7. Major trauma/surgery within 4 weeks prior to treatment initiation.
4. Clinically significant gastrointestinal abnormalities, including:

   * Moderate/severe atrophic gastritis
   * GI obstruction/perforation
   * Chronic diarrhea/short bowel syndrome
   * Major upper GI surgery (e.g., gastrectomy)
   * Inflammatory bowel disease (Crohn's/ulcerative colitis) or active intestinal inflammation
   * Inability to swallow tablets
5. Uncontrolled systemic diseases.
6. Severe acute/chronic infections.
7. Interstitial lung disease (ILD)/non-infectious pneumonia:

   * History requiring clinical intervention
   * Current presence
   * Suspicious imaging findings unresolved at screening
8. Clinically significant cardiovascular dysfunction (active or history).
9. Tumor invasion of critical adjacent structures (heart/esophagus/SVC etc.) with high bleeding/fistula risk. Exceptions may be considered if investigator assesses minimal risk.
10. Pulmonary comorbidities causing severe impairment, including:

    1. Baseline lung diseases (e.g., pulmonary embolism \[≤3 months\], severe asthma/COPD/restrictive disease)
    2. Autoimmune/connective tissue disorders with pulmonary involvement (e.g., rheumatoid arthritis, sarcoidosis)
11. Residual toxicity \>Grade 1 (per NCI CTCAE v5.0) from prior anticancer therapy (except alopecia/neuropathy).
12. Concurrent malignancies except:

    * Cured localized skin cancers (BCC/SCC), superficial bladder cancer, cervical/breast DCIS, or papillary thyroid cancer
    * Other malignancies cured by radical therapy ≥3 years prior
13. Pregnancy/lactation or planned pregnancy within 6 months post-treatment.
14. Inability to comply with study procedures/follow-up.
15. Known hypersensitivity to furmonertinib or excipients.
16. History of allergic reactions to pemetrexed/cisplatin/carboplatin.
17. Other exclusionary per investigator judgment, including:

    * Alcohol/drug abuse
    * Severe comorbidities (including psychiatric) requiring treatment
    * Critical laboratory abnormalities
    * Social/familial factors compromising safety/data collection