Hypofractionated Chemoradiotherapy With Tislelizumab and Surufatinib for Unresectable Stage III NSCLC

A Randomized Phase 2 Study of Hypofractionated Concurrent Chemoradiotherapy Combined With Tislelizumab and Surufatinib in Patients With Unresectable Stage III Non-Small Cell Lung Cancer

This phase II trial employs a prospective, randomized, parallel-group design to evaluate the efficacy and safety of hypofractionated radiotherapy combined with tislelizumab and surufatinib. Eligible patients are randomly assigned to one of two arms: Experimental Group A receives hypofractionated chemoradiotherapy plus concurrent tislelizumab and surufatinib, followed by consolidation therapy with tislelizumab plus surufatinib; Experimental Group B receives the same hypofractionated chemoradiotherapy plus concurrent tislelizumab alone, followed by tislelizumab consolidation.

Inclusion Criteria:

• Males or females aged 18 to 75 years or older;
• Patients must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC);
• Unresectable Stage III disease according to AJCC 8th staging system;
• Negative for known driver gene mutations；
• Newly diagnosed patients or patients treated with ≤ 4 cycles of chemotherapy combined with or without immunotherapy;
• Expected survival ≥ 12 weeks;
• WHO Performance Status (PS) score of 0 or 1;
• Female subjects must not be breastfeeding;
• Women of childbearing potential (WOCBP) must agree to use contraception during the study treatment and for 5 months after the last dose of study drug (i.e., 30 days [one ovulation cycle] plus approximately five half-lives of the study drug);
• Adequate organ and bone marrow function as defined by the following criteria:
• Forced Expiratory Volume in 1 second (FEV1) ≥ 800 mL;
• Absolute neutrophil count ≥ 1.5 × 10⁹/L;
• Platelets ≥ 100 × 10⁹/L;
• Hemoglobin ≥ 9.0 g/dL;
• Creatinine clearance ≥ 50 mL/min as calculated by the Cockcroft-Gault formula (Cockcroft and Gault, 1976);
• Serum bilirubin ≤ 1.5 × upper limit of normal (ULN);
• AST and ALT ≤ 2.5 × ULN.

Exclusion Criteria:

• Concurrent enrolment in another clinical study, unless it is an observational(non-interventional) clinical study;
• Mixed small cell and non-small cell lung cancer histology;
• Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access;
• Active or prior documented autoimmune disease within the past 2 years;
• Active or prior documented inflammatory bowel disease (eg. Crohn's disease, ulcerative colitis);
• History of primary immunodeficiency;
• History of organ transplant that requires therapeutic immunosuppression;
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent;
• Known history of tuberculosis;
• History of another primary malignancy within 5 years prior to starting treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study;
• Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.