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

Korábbi kezelés

• 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

Más betegség

• 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.

Laborértékek

• 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

Egyéb

• 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.

• 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.