Hypofractionated Chemoradiotherapy Followed by Consolidative Immunotherapy Versus Conventional Fractionated Chemoradiotherapy Followed by Consolidative Immunotherapy in Locally Advanced Non-small Cell Lung Cancer: A Randomized, Phase III Controlled Study
Consolidative immunotherapy following concurrent chemoradiotherapy, based on the PACIFIC trial, has become the standard treatment for locally advanced non-small cell lung cancer (LANSCLC). Radiotherapy strategies for maximizing efficacy and local control require further investigation. This phase III, randomized controlled clinical trial is to investigate the efficacy and safety of hypofractionated chemoradiotherapy followed by consolidative immunotherapy versus conventional fractionated chemoradiotherapy followed by consolidative immunotherapy in LANSCLC patients.
• 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