Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
- Signed and Dated Informed Consent: Written informed consent must be provided prior to any study procedures, with the consent form signed and dated by the participant.
- Age Range: Male or female patients aged 18 to 75 years.
- Diagnosis: Patients must have locally advanced, unresectable (stage III) non-small cell lung cancer (NSCLC), with histological or cytological confirmation of the diagnosis.
- Previous Treatment: Treatment-naïve or previously treated with induction chemotherapy ± immunotherapy.
- Tumor Sample Requirement: Tumor tissue samples must be provided, and they should be sufficient for analysis. The samples must be unstained and archived.
- Driver gene testing: EGFR wild-type, ALK rearrangement-negative.
- Life Expectancy: Patients must have an expected survival of at least 12 weeks.
- Performance Status (PS): The patient's WHO Performance Status (PS) must be 0 or 1.
- Pregnancy Testing: Postmenopausal women, or women who have had a negative urine or serum pregnancy test within 14 days before the study medication (HCG sensitivity ≥ 25 IU/L or equivalent).
- Breastfeeding: Women must not be breastfeeding.
- Women of childbearing potential (WOCBP) must agree to use contraception during the study treatment period and for 5 months after the last dose of the investigational drug (i.e., 30 days [ovulation cycle] + approximately 5 half-lives of the study drug).
- Men who have sexual relations with WOCBP must agree to use contraception during the study treatment period and for 7 months after the last dose of the investigational drug (i.e., 90 days [sperm renewal cycle] + approximately 5 half-lives of the study drug).
- Males with no sperm production are exempt from contraception requirements. WOCBP who are not sexually active are exempt from contraception but must still undergo pregnancy testing as outlined above.
- Organ and Bone Marrow Function: The following laboratory parameters must be met:
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 Calculated creatinine clearance using the Cockcroft-Gault formula ≥ 50 mL/min Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) AST and ALT ≤ 2.5 × ULN
Exclusion criteria
- 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.
- 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.
