This study explores how adjuvant therapy affects survival in completely resected high-risk stage IA-IB NSCLC patients with different driver gene mutations.

This study aims to evaluate whether tailored, targeted therapy or immunotherapy can effectively prevent cancer recurrence in patients with early-stage (stage IA-IB) non-small cell lung cancer (NSCLC) who have undergone complete surgical resection but are at high risk of recurrence. Based on each patient's specific driver gene mutation status (e.g., EGFR or ALK/ROS1) or wild-type status, participants will receive either targeted therapy or immunotherapy compared to routine follow-up (observation). The goal is to see if these approaches can improve disease-free survival and potentially reduce the risk of lung cancer recurrence.

Inclusion Criteria:

• Age 18-75 years and able to provide written informed consent.
• Primary non-squamous NSCLC confirmed by pathology, with no brain metastases.
• Complete R0 surgical resection (lobectomy, segmentectomy, or pneumonectomy) of stage IA or IB NSCLC (AJCC 8th edition).
• High-risk disease (one or more): low differentiation, solid/micropapillary/complex glandular patterns, vascular invasion, visceral pleural invasion, alveolar space spread, or intermediate/high risk on 14-gene test.
• Documented driver gene status (EGFR mutation, ALK/ROS1 fusion, or wild-type) via postoperative tumor sample.
• ECOG performance status 0 or 1, with stable condition over the last two weeks.
• Surgery within 4-10 weeks before starting treatment, with full recovery.
• Adequate organ function as per protocol-defined labs.
• Negative pregnancy test (if applicable) and use of effective contraception during and 3 months after treatment.

Exclusion Criteria:

• Evidence of unresectable/metastatic NSCLC, incomplete resection (R1/R2), or wedge resection only.
• Prior systemic therapy (e.g., chemotherapy, targeted therapy, immunotherapy) for the current NSCLC.
• Major surgery (excluding lung cancer surgery) within 3 weeks before first study dose.
• Planned concurrent anti-cancer therapy (chemo, radiotherapy, or targeted therapy) during the study.
• Clinically significant cardiac disorders (e.g., poorly controlled hypertension, recent MI or stroke, prolonged QTc).
• History or suspicion of interstitial lung disease requiring treatment.
• Active or uncontrolled infection (e.g., hepatitis B with detectable HBV DNA, hepatitis C, HIV, active TB).
• Severe GI conditions impairing drug absorption (e.g., Crohn's, ulcerative colitis).
• Use of strong CYP3A inducers/inhibitors within 1 week or ongoing need for warfarin.
• Participation in another interventional trial within 4 weeks or receipt of a live vaccine within 180 days.
• Any condition that may compromise adherence or safety, per investigator judgment.