Firmonertinib Versus Platinum Based Chemotherapy as First-line Treatment for NSCLC With EGFR PACC or EGFR l861q Mutation

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