Firmonertinib compared with platinum chemotherapy for lung cancer with EGFR mutations

Who can take part

• Voluntarily sign the informed consent form (ICF)
• Age ≥18 years at the time of ICF signing
• 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
• 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)
• 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.)
• No prior systemic therapy for advanced/metastatic NSCLC; Allowed if: Prior (neo)adjuvant/definitive chemoradiotherapy completed ≥12 months before recurrence/progression
• ECOG performance status 0-1
• Life expectancy ≥12 weeks
• Adequate bone marrow/organ function within 14 days before treatment (no transfusion/G-CSF within 2 weeks prior)
• Women of childbearing potential (WOCBP):; Abstinence or contraception use; No egg donation
• Non-sterilized males:; Abstinence or contraception use; No sperm donation
• CNS metastases allowed if protocol-specified criteria are met

Who cannot take part

• 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
• Residual toxicity >Grade 1 (per NCI CTCAE v5.0) from prior anticancer therapy (except alopecia/neuropathy)
• 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
• 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
• Uncontrolled systemic diseases
• Severe acute/chronic infections
• Interstitial lung disease (ILD)/non-infectious pneumonia:; History requiring clinical intervention; Current presence; Suspicious imaging findings unresolved at screening
• Tumor invasion of critical adjacent structures (heart/esophagus/SVC etc.) with high bleeding/fistula risk. Exceptions may be considered if investigator assesses minimal risk
• Pulmonary comorbidities causing severe impairment, including:; Baseline lung diseases (e.g., pulmonary embolism [≤3 months], severe asthma/COPD/restrictive disease); Autoimmune/connective tissue disorders with pulmonary involvement (e.g., rheumatoid arthritis, sarcoidosis)
• Known hypersensitivity to furmonertinib or excipients
• History of allergic reactions to pemetrexed/cisplatin/carboplatin
• Prior treatments including:; Systemic anti-tumor therapy for advanced/metastatic NSCLC (e.g., chemotherapy/targeted/immunotherapy). Neoadjuvant/adjuvant therapy exceptions per Inclusion Criterion #6; >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); Any prior EGFR-targeted therapy (including investigational EGFR-TKIs, mAbs, bispecific antibodies, etc.); Strong CYP3A4 inhibitors within 7 days or inducers within 21 days prior to first dose; Anticancer traditional Chinese medicines within 2 weeks prior to first dose; Non-specific immunomodulators (e.g., interferon, IL-2, thymosin) within 2 weeks prior to first dose; Major trauma/surgery within 4 weeks prior to treatment initiation
• 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
• Histologically/cytologically confirmed tumor with >10% neuroendocrine carcinoma, sarcomatoid carcinoma, or squamous cell components
• Clinically significant cardiovascular dysfunction (active or history)
• Pregnancy/lactation or planned pregnancy within 6 months post-treatment
• Inability to comply with study procedures/follow-up