This is a single-arm, open-label, multicenter phase II investigator-initiated trial. The study aims to explore the efficacy and safety of Adebrelimab plus Trastuzumab rezetecan induction therapy in patients with stage III unresectable HER2-altered non-small cell lung cancer (NSCLC). Eligible patients receive 3-4 cycles Q3W induction combination therapy. After induction, patients will receive radical surgery or concurrent chemoradiotherapy via MDT evaluation, followed by consolidation therapy and long-term survival follow-up. The primary endpoint is objective response rate (ORR) assessed per RECIST v1.1. Secondary endpoints include surgical conversion rate, major pathological response (MPR), event-free survival (EFS), overall survival (OS), and safety profiles.
Aged 18-75 years, male or female.
Histologically or cytologically confirmed stage III unresectable NSCLC per AJCC 9th edition, judged unresectable by institutional MDT team.
Confirmed HER2 alteration: HER2 mutation/amplification detected by tissue NGS, or HER2 protein overexpression (IHC 2+ or 3+).
No prior systemic anti-tumor therapy for NSCLC; prior anti-tumor Chinese herbal medicine allowed if ≥2 weeks washout before first dose.
Mixed small cell/large cell neuroendocrine/sarcomatoid NSCLC histology.
Concurrent other actionable driver gene alterations (EGFR, ALK, MET, BRAF, RET etc.) besides HER2.
Past or concurrent other malignant tumor (except fully resected cancer ≥5 years without active treatment).
Prior thoracic radiotherapy.