Neoadjuvant Immunotherapy Plus Chemotherapy Followed by Concurrent Chemoradiotherapy and Consolidative Immunotherapy for Locally Advanced Non-small Cell Lung Cancer

Exclusion Criteria28

• Patients meeting any of the following criteria should not be enrolled in the study:
• Concurrent participation in another clinical trial, except for observational (non-interventional) studies.
• Histological subtype of mixed small-cell and non-small-cell lung cancer. Use of immunosuppressive drugs within 28 days before treatment, except for intranasal or inhaled corticosteroids at physiological doses or systemic corticosteroids ≤10 mg/day of prednisone or equivalent.
• Prior treatment with anti-PD-1 or anti-PD-L1 antibodies.
• Major surgery within 4 weeks prior to enrollment (excluding procedures for vascular access).
• History or active autoimmune diseases within the past two years.
• Active or a history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of organ transplantation requiring immunosuppressive therapy.
• Average corrected QT interval (QTc) ≥470 ms calculated from three ECG cycles using the Bazett formula.
• Uncontrolled comorbidities, including but not limited to: Persistent or active infections. Symptomatic congestive heart failure. Poorly controlled hypertension. Unstable angina. Cardiac arrhythmias. Active peptic ulcer disease or gastritis. Active bleeding disorders. Hepatitis C or HIV infection. HBsAg-positive patients with HBV DNA \>500 IU/mL. Mental or social conditions that may limit adherence to study requirements or compromise the ability to provide informed consent.
• Known history of tuberculosis.
• Receipt of a live attenuated vaccine within 30 days before study initiation or planned during the study period.
• History of another primary malignancy within the past 5 years, except for adequately treated basal or squamous cell carcinoma of the skin or in situ cervical cancer.
• Pregnancy, breastfeeding, or not using effective contraception (for men and women of reproductive potential).
• Patients in the experimental group should not proceed to concurrent chemoradiotherapy if any of the following criteria are met:
• Presence of distant metastases.
• Locoregional progression making definitive concurrent chemoradiotherapy unfeasible due to normal tissue dose constraints (assessed by the radiation oncologist).
• WHO performance status score of 2-4.
• Impaired organ or bone marrow function, including:
• Forced expiratory volume in 1 second (FEV1) \<800 mL. Absolute neutrophil count (ANC) \<1.5 × 10⁹/L. Platelets \<100 × 10⁹/L. Hemoglobin \<9.0 g/dL. Creatinine clearance (Cockcroft-Gault formula) \<50 mL/min. Serum bilirubin \>1.5 × upper limit of normal (ULN). AST and ALT \>2.5 × ULN.
• \- Patient withdrawal from the study.
• Patients should not proceed to consolidation immunotherapy if any of the following criteria are met:
• Disease progression during concurrent chemoradiotherapy.
• Use of immunosuppressive drugs within 28 days before the first dose of tislelizumab, except for physiological doses of intranasal or inhaled corticosteroids or systemic corticosteroids ≤10 mg/day of prednisone or equivalent. Use of corticosteroids to manage chemoradiotherapy-related toxicity is permitted.
• Persistent unresolved CTCAE grade \>2 toxicities from prior chemoradiotherapy.
• Grade ≥2 pneumonitis resulting from prior chemoradiotherapy.
• Any prior grade ≥3 immune-related adverse event (irAE) or unresolved irAE \> grade 1.