This is a single-center, single-arm, phase 2 trial evaluating the efficacy and safety of retlirafusp alfa combined with single-agent chemotherapy as neoadjuvant treatment for patients with resectable stage II-III EGFR/ALK wild-type non-small cell lung cancer (NSCLC).Eligible patients receive 4 cycles of neoadjuvant therapy, followed by curative surgery and 1-year maintenance therapy with retlirafusp alfa.Primary endpoints are pathological complete response (pCR) rate and safety. Secondary endpoints include major pathological response (MPR), event-free survival (EFS), and overall survival (OS).

Inclusion Criteria:

• Age 18-75 years
• ECOG Performance Status 0-1;
• Treatment-naive patients with histologically or cytologically confirmed NSCLC (via biopsy) and radiologically confirmed Stage II-III disease;
• Patients with adenocarcinoma must be confirmed to be free of driver gene mutations such as EGFR or ALK; patients with squamous cell carcinoma do not require genetic testing;
• Patients must have measurable lesions;
• Patients whose disease was assessed as CR, PR, or SD following 2 cycles of neoadjuvant chemotherapy with Rilpufan α in combination with a single-agent non-platinum chemotherapy;
• Life expectancy of at least 12 weeks;
• Good function of other major organs (liver, kidneys, hematopoietic system, etc.): - Hemoglobin ≥ 9.0 g/dL (this level may be maintained or exceeded through blood transfusion); - Red blood cell count ≥ 2.0 × 10⁹/L; - Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; - Platelet count ≥ 100 × 10⁹/L; - Total bilirubin within normal limits; - Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase ≤ 2.5 times the upper limit of normal; - Creatinine ≤ 2.0 mg/dL; and creatinine clearance ≥ 60 mL/min; - For patients who have not received anticoagulant therapy: International Normalized Ratio (INR) for prothrombin time ≤ 1.5, and activated partial thromboplastin time (APTT) ≤ 1.5 times the upper limit of normal. Patients receiving full-dose or parenteral anticoagulant therapy may be enrolled in the clinical trial provided that the anticoagulant dose has been stable for at least 2 weeks prior to study entry and the results of coagulation tests fall within the limits established by the local treatment center.
• No systemic metastases;
• Expected to be completely resectable;
• Good pulmonary function sufficient to tolerate surgical treatment;
• Women of childbearing potential must undergo a pregnancy test within 7 days prior to the start of treatment and receive a negative result;
• Participants must use reliable contraception (e.g., intrauterine device, oral contraceptives, and condoms) during the trial and for 30 days after its completion; 14 Participants voluntarily enroll in the study, sign an informed consent form, demonstrate good compliance, and cooperate with follow-up.

Exclusion Criteria:

• Any systemic anticancer therapy for NSCLC, other than neoadjuvant therapy as specified in the inclusion criteria, including surgery, local radiotherapy, cytotoxic drug therapy, targeted drug therapy, and experimental treatments;
• Patients who have had a cancer other than NSCLC within five years prior to the start of this trial;
• Patients with unstable systemic diseases, such as uncontrolled hypertension or severe arrhythmias;
• Patients with active, known, or suspected autoimmune diseases;
• Patients with a history of or current interstitial lung disease;
• Patients with HIV infection;
• Patients who have undergone major systemic surgery or suffered severe trauma within 2 months prior to the start of this trial;
• Pregnant or breastfeeding women;
• Patients with neurological or psychiatric disorders who are unable to comply with the study protocol;
• Other circumstances deemed unsuitable for enrollment by the investigator