Phase II Neoadjuvant Study of Garsorasib Followed by Ivonescimab Plus Chemotherapy in Resectable Stage IIA-IIIB KRAS G12C-Mutant NSCLC (GIVEN Study)

This study is a multicenter, prospective, open-label clinical trial. It enrolls previously untreated patients with resectable stage IB-IIIB KRAS G12C mutation-positive NSCLC to evaluate the efficacy and safety of glesorasib sequentially combined with ivonescimab and chemotherapy as perioperative treatment for this patient population.

Inclusion Criteria: 1. Age Range: Males or females aged 18 years or older. 2. Diagnosis and Stage: Patients with histologically or cytologically confirmed resectable IB-IIIB NSCLC, staged according to the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology, 9th Edition. 3. Informed Consent: Patients must voluntarily participate in the study, provide written informed consent, and be willing to comply with follow-up procedures. 4. Prior Therapy: No prior systemic therapy for locally advanced or metastatic NSCLC (including adjuvant chemo/radiotherapy, neoadjuvant chemo/radiotherapy, definitive chemoradiotherapy, chemotherapy, radiotherapy, immune checkpoint inhibitors, targeted therapy, or anti-angiogenic therapy for locally advanced disease). 5. Mutation Status: KRAS G12C mutation positivity must be confirmed by next-generation sequencing (NGS) or polymerase chain reaction (PCR) testing. 6. Measurable Disease: At least one measurable target lesion as per RECIST v1.1. Lesions previously treated with radiotherapy or other local-regional therapies cannot be considered target lesions unless clear progression has been documented post-radiotherapy. At baseline, the lesion must be ≥10mm in the longest diameter (≥15mm in short axis for lymph nodes) on CT or MRI and be suitable for accurate repeated measurement per RECIST v1.1. 7. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 8. Adequate Organ Function: Must meet the following criteria within 14 days prior to relevant tests, without transfusion or use of hematopoietic growth factors: 1. Platelets (PLT) ≥90 × 10\^9/L 2. Hemoglobin (HGB) ≥90 g/L 3. Absolute Neutrophil Count (ANC) ≥1.5 × 10\^9/L 4. Serum creatinine ≤1.5 × ULN or Creatinine Clearance (CrCl) ≥50 mL/min (calculated using the Cockcroft-Gault formula) 5. Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if liver metastases are present) 6. Total Bilirubin (TBIL) ≤1.5 × ULN (≤3 × ULN for patients with Gilbert's syndrome) 7. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 × ULN, and Activated Partial Thromboplastin Time (APTT) ≤1.5 × ULN, or patients assessed by the investigator as having controlled bleeding tendency. 8. Urinalysis showing urine protein \ 470 ms for females, \> 450 ms for males) or risk factors for Torsades de Pointes. 6. Uncontrolled hypertension (systolic BP ≥ 150 mmHg and/or diastolic BP ≥ 100 mmHg after antihypertensive therapy). 15. Thromboembolic Events: Arterial/venous thrombotic events within 6 months, hypertensive crisis, or hypertensive encephalopathy. 16. History of Epilepsy: Previous history of epilepsy. 17. Superior Vena Cava Syndrome: Presence of superior vena cava syndrome. 18. Pulmonary Disease: Active non-infectious interstitial lung disease, radiation pneumonitis, etc., active tuberculosis, pneumoconiosis, ≥ Grade 2 other pneumonias, or severely impaired pulmonary function at screening. 19. Severe Bone Lesions: Existing or potential severe bone damage from metastases, or uncontrolled bone pain. 20. Active Infection: Active or uncontrolled severe infection, or unexplained fever \> 38.5°C. 21. Third-Space Fluid: Poorly controlled or drainage-requiring pleural effusion, ascites, or pericardial effusion. Subjects stabilized after treatment may be enrolled. 22. Tumor Invading Major Vessels: Imaging shows tumor invading or with unclear boundaries to major blood vessels. 23. Bleeding Risk: Evidence or history of bleeding tendency within 2 months before the first dose; history of hemoptysis, or unhealed wounds/ulcers/fractures within 2 weeks before the first dose. 24. Gastrointestinal Diseases: Known GI impairment or diseases significantly affecting drug absorption/metabolism, or major GI surgery affecting absorption. 25. Recent Live Vaccination: Administration of a live attenuated vaccine within 4 weeks before the first dose. 26. Severe Hypersensitivity to mAbs: History of severe hypersensitivity reaction to other monoclonal antibodies. 27. Autoimmune Disease: Active autoimmune disease requiring systemic treatment within 2 years before the first dose. 28. Immunosuppressive Therapy: Receiving systemic corticosteroids or other immunosuppressive therapy. 29. Viral Infections: Positive HIV antibody, or active viral hepatitis. 1. Active Hepatitis B or active Hepatitis C. 2. Carriers require antiviral therapy and monitoring during the study. 30. Active Syphilis. 31. Renal Failure: Requiring hemodialysis or peritoneal dialysis. 32. Poorly Controlled Diabetes: Fasting blood glucose \> 10 mmol/L. 33. Organ Transplant: History of or planned organ transplantation. 34. Recent Major Surgery/Trauma: Major surgery or significant trauma within 4 weeks before the first dose. 35. Recent Radiotherapy: Palliative radiotherapy within 2 weeks before the first dose. 36. Residual Toxicity from Prior Therapy: Toxicities from previous anti-cancer therapy not recovered to Grade ≤1. 37. Other: Any other clinically significant abnormality or disease deemed by the investigator to pose risk or interfere with the study.