This is a prospective, open, single-center, single-arm phase II clinical study in non-small cell lung cancer (NSCLC) without common EGFR-sensitive mutations (Ex19del and L858R) or ALK fusion variants identified in the central laboratory. To evaluate the efficacy and safety of neoadjuvant therapy of sacituzumab tirumotecan combined with toripalimab.

Inclusion Criteria:

1. Age ≥18 years at the time of informed consent signing, either sex;

2. ECOG performance status score of 0-1 within 7 days prior to dosing;

3. Histologically or cytologically confirmed NSCLC;

4. Negative for EGFR sensitive mutations (no exon 19 deletion or exon 21 L858R substitution mutation) and negative for ALK fusion gene;

5. No prior local treatment (surgery or radiotherapy) for NSCLC and no prior systemic antineoplastic therapy, including cytotoxic therapy, targeted therapy (including tyrosine kinase inhibitors or monoclonal antibodies), cellular therapy, immunotherapy, traditional Chinese medicine therapy, and any other investigational drug therapy;

6. Patients with resectable stage II-IIIB NSCLC as assessed by MDT (according to UICC/AJCC 8th edition TNM staging);

7. At least one measurable lesion (according to RECIST 1.1 criteria);

8. Patients who agree to undergo radical surgical treatment;

9. Surgical evaluation confirms operability with no contraindications to surgery;

10. Adequate organ and bone marrow function (no transfusion, recombinant human thrombopoietin, or colony-stimulating factor treatment within 2 weeks prior to first dosing), defined as follows:

    1. Hematology: Absolute neutrophil count (NEUT#) ≥ 1.5×10⁹/L; Platelets (PLT) ≥ 100×10⁹/L; Hemoglobin ≥ 90 g/dL;
    2. Hepatic function: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP) ≤ 2.5×upper limit of normal (ULN); Total bilirubin (TBIL) ≤ 1.5×ULN;
    3. Renal function: Creatinine clearance (Ccr) ≥ 60 ml/min (Cockcroft-Gault formula, see Appendix);
    4. Coagulation function: International normalized ratio (INR), Activated partial thromboplastin time (APTT), and Prothrombin time (PT) ≤ 1.5×ULN;
    5. Cardiac function: Echocardiography (ECHO) or Multiple gated acquisition (MUGA) scan showing left ventricular ejection fraction (LVEF) ≥ 50%;

11. For female subjects of childbearing potential and male subjects with partners of childbearing potential, must agree to use effective medical contraception from the time of informed consent signing until 6 months after the last dose (see Appendix 2 for details);

12. Subjects voluntarily participate in this study, sign informed consent, and are able to comply with protocol-specified visits and related procedures.

Exclusion Criteria:

1. Histologically or cytologically confirmed combined small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma components;
2. Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies, or any other antibodies or drugs specifically targeting T-cell co-stimulation or checkpoint pathways;
3. Prior treatment with TROP2-targeted therapy and/or topoisomerase I inhibitors;
4. Requirement for strong inhibitors or inducers of cytochrome P450 3A4 enzyme (CYP3A4) within 2 weeks prior to first dosing and during the study (strong CYP3A4 inhibitors or inducers are not permitted in this study; Appendix 6 lists representative drugs of strong CYP3A4 inhibitors or inducers); all subjects must avoid concomitant use of any drugs, herbal supplements, and/or foods known to induce CYP3A4.
5. Other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma, or cutaneous squamous cell carcinoma;
6. Known history of hypersensitivity to study drugs and their components, history of immunodeficiency, or history of organ transplantation;
7. History of interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment (non-infectious), current ILD or non-infectious pneumonitis, or suspected ILD or non-infectious pneumonitis that cannot be excluded by imaging at screening; clinically significant pulmonary impairment due to pulmonary comorbidities, including but not limited to any underlying pulmonary disease (such as pulmonary embolism within 3 months prior to dosing, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.) or any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (i.e., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or prior pneumonectomy;
8. Active autoimmune disease requiring systemic treatment within the past 2 years (hormone replacement therapy is not considered systemic treatment, such as type 1 diabetes, hypothyroidism requiring only thyroid hormone replacement therapy, adrenal or pituitary insufficiency requiring only physiologic doses of glucocorticoid replacement therapy);
9. Active infection requiring systemic treatment within 2 weeks prior to first dosing;
10. Active hepatitis B [hepatitis B surface antigen (HBsAg) positive, HBV-DNA testing required; HBV-DNA ≥ 500 IU/mL or above the lower limit of detection, whichever is higher] or hepatitis C (hepatitis C antibody positive, and HCV-RNA above the lower limit of detection). Note: For HBsAg-positive subjects, anti-hepatitis B virus treatment is required during study treatment;
11. Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection;
12. Severe concomitant diseases that endanger patient safety or affect study completion, as judged by the investigator, including but not limited to uncontrolled hypertension with medication, severe diabetes, active infection, etc.;
13. Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or history of corneal disease that prevents delayed corneal healing;
14. Pregnant or lactating women;
15. Any condition that interferes with the evaluation of study drugs, subject safety, or interpretation of study results, or any other condition deemed by the investigator as unsuitable for participation in this study.