This is a prospective, single-arm, phase II clinical study designed to evaluate the efficacy and safety of surufatinib and tislelizumab in combination with concurrent chemoradiotherapy, followed by consolidation therapy with tislelizumab plus surufatinib, in patients with unresectable, locally advanced stage III non-small cell lung cancer (NSCLC).

In this study, all enrolled patients will initially receive definitive concurrent chemoradiotherapy combined with surufatinib and tislelizumab. Patients who achieve complete response (CR), partial response (PR), or stable disease (SD) following the aforementioned treatment will proceed to receive consolidation therapy with surufatinib and tislelizumab. Surufatinib will be administered orally at a dose of 200 mg once daily (QD) for 2 consecutive weeks followed by a 1-week break, with each cycle lasting 3 weeks (21 days). Concurrently, tislelizumab will be administered intravenously at 200 mg every 3 weeks (Q3W), for up to a maximum duration of 12 months.

Inclusion Criteria:

• A written and dated informed consent form must be obtained prior to the initiation of any study-specific procedures.
• Male or female patients aged 18 to 75 years.
• Histologically or cytologically confirmed locally advanced, unresectable non-small cell lung cancer (NSCLC) (Stage IIIA-IIIC).
• Tumor sample requirement: Adequate archival, unstained tumor tissue samples must be provided for analysis.
• Expected life expectancy of ≥12 weeks.
• World Health Organization (WHO) performance status (PS) score of 0 or 1.
• Postmenopausal women, or negative urine or serum pregnancy test (with a minimum sensitivity of 25 IU/L or equivalent for HCG) within 14 days prior to receiving study medication.
• Female participants must not be breastfeeding.
• Women of childbearing potential (WOCBP) must agree to use effective contraception during the study treatment period and for 6 months after the last dose of study drug.
• Male participants who are sexually active with WOCBP must agree to use effective contraception during the study treatment period and for 6 months after the last dose of study drug.
• Male participants with azoospermia are exempt from contraceptive requirements. WOCBP who are not heterosexually active are also exempt from contraceptive use but must still undergo pregnancy testing as specified above.
• Adequate organ and bone marrow function as defined by the following criteria: Forced expiratory volume in 1 second (FEV1) ≥ 800 mL; Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; Hemoglobin ≥ 9.0 g/dL; Serum creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula; Cockcroft and Gault, 1976); Total serum bilirubin ≤ 1.5 × upper limit of normal (ULN); AST and ALT ≤ 2.5 × ULN

Exclusion Criteria:

• Participation in another clinical study, unless it is an observational (non-interventional) study.
• Histological diagnosis of combined small cell and non-small cell lung cancer.
• Presence of EGFR or ALK driver gene mutations.
• Any condition that may affect oral medication administration (e.g., dysphagia, chronic diarrhea, bowel obstruction).
• Major surgery within 4 weeks prior to study entry (excluding vascular access procedures).
• Average QT interval corrected for heart rate (QTc) ≥ 470 ms, calculated using Bazett's formula from three ECG cycles.
• Uncontrolled comorbidities, including but not limited to: ongoing or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, clinically significant arrhythmias, active peptic ulcer disease or gastritis, active bleeding disorders, or patients who are HBsAg-positive with HBV DNA > 500 IU/mL, hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. Also excluded are individuals with psychiatric or social conditions that may interfere with study compliance or the ability to provide written informed consent.
• History of another primary malignancy within 5 years prior to study treatment initiation, except for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• Pregnant or breastfeeding women; or women and men of reproductive potential who are not using effective contraception.
• Use of immunosuppressive medications within 28 days prior to the first dose of tislelizumab, excluding intranasal corticosteroids at physiological doses and systemic corticosteroids at a dose equivalent to ≤10 mg/day of prednisone.
• History of autoimmune disease or active autoimmune disease within the past 2 years.
• Active or prior history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of organ transplantation requiring immunosuppressive therapy.
• Receipt of a live attenuated vaccine within 30 days prior to study initiation or within 30 days after receiving tislelizumab.
• Any condition that, in the investigator's judgment, may interfere with the assessment of efficacy or safety of the study treatment.