This is an open-label, randomized, controlled, multicenter phase III clinical trial designed to evaluate the efficacy and safety of spatially fractionated stereotactic body radiotherapy (SF-SBRT) combined with toripalimab and platinum-based chemotherapy versus toripalimab combined with platinum-based chemotherapy in patients with resectable or potentially resectable stage II-III non-small cell lung cancer (NSCLC). Eligible participants will be randomized 2:1 to receive either neoadjuvant SF-SBRT followed by toripalimab and platinum-based chemotherapy for two cycles, or toripalimab and platinum-based chemotherapy for three cycles. Randomization will be stratified by disease stage and histological subtype. Surgery is planned 4-6 weeks after completion of neoadjuvant treatment, and postoperative adjuvant therapy will be determined by the investigator. The primary endpoint is the 2-year event-free survival rate. Secondary endpoints include pathological complete response rate, major pathological response rate, objective response rate, R0 resection rate, event-free survival, overall survival, and safety. Adverse events will be assessed according to NCI CTCAE version 5.0 or later.
Male or female participants aged 18 to 75 years;
Eastern Cooperative Oncology Group performance status of 0 or 1;
Previously untreated, pathologically confirmed, resectable or potentially -resectable stage II, IIIA, or IIIB (N2) non-small cell lung cancer according to the 8th edition of the American Joint Committee on Cancer staging system;
At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1;
Locally advanced unresectable or metastatic disease. Unresectable disease is defined according to the multidisciplinary consensus for stage III non-small cell lung cancer (2019 edition), including some stage IIIA, stage IIIB, and all stage IIIC disease. This usually includes N2 disease with a single-station mediastinal lymph node with a short-axis diameter ≥3 cm, or multistation lymph node fusion/conglomeration with lymph nodes having a short-axis diameter ≥2 cm on CT; T4 disease invading the esophagus, heart, aorta, or pulmonary veins; and all N3 disease;
Non-small cell lung cancer involving the superior sulcus, large-cell neuroendocrine carcinoma, or sarcomatoid carcinoma;
Known sensitizing EGFR mutation or ALK rearrangement. For participants with non-squamous histology, EGFR and ALK mutation status must be confirmed;
Prior treatment with PD-1 or PD-L1 inhibitors, or agents targeting another T-cell receptor pathway, such as CTLA-4 or OX-40;