Stage II-III Non-small Cell Lung Cancer Clinical Trial
Official title:
Neoadjuvant Therapy of SBRT Sequencial With Toripalimab and Chemotherapy in Resectable Stage II-III NSCLC Patients: A Multicenter, Openlabel, Randomized, Phase III Trial
This is a randomized, controlled, multi-center, phase III clinical study to evaluate the efficacy and safety of SBRT sequencial with Toripalimab and chemotherapy versus Toripalimab and chemotherapy for subjects with resectable, stage II-III NSCLC.
Subjects who meet all the inclusion criteria but do not meet any exclusion criteria are randomized into two groups at a ratio of 1:1: according to the stratification factors as below: - Disease stage: II vs IIIA vs IIIB - PD-L1 status: PD-L1 expression ≥1% vs. PD-L1 <1% or not evaluable - Pathological type: non-squamous cell carcinoma vs. squamous cell carcinoma Neoadjuvant therapy should be started within 1 week after randomization. Stereotactic body radiation therapy (SBRT) will be given for primary lung tumor, 24Gy/3fractions, sequential toripalimab IV 240 mg Q3W will be given combined with platinum-based doublet drug chemotherapy for three cycles in the preoperative neoadjuvant therapy period for trial group; the controlled group receive toripalimab IV 240 mg Q3W combined with platinum-based doublet drug chemotherapy for three cycles in the preoperative neoadjuvant therapy period. Every 3 weeks of treatment is regarded as one cycle, in which combined therapy is given in the first day of every cycle. All the subjects will receive preoperative radiological and surgical evaluation 4-6 weeks after neoadjuvant therapy. After 3 cycles of preoperative neoadjuvant therapy, all the subjects who still have surgical indications will receive radical excision based on the surgical operation criteria of the World Association for Lung Cancer Research within 4-6 weeks after 3 cycles of preoperative neoadjuvant therapy. The pTNM will be staged in accordance with AJCC Cancer Staging Manual (version 8). All the specimens taken during the operation will be evaluated by local pathologists for the surgical margin. The tumor tissue samples collected from subjects during the study will be submitted to the authorized central laboratory for blinded evaluation of pathological response and translational research. All the subjects who have completed the radical operation will receive one cycle of postoperative adjuvant therapy, i.e., Toripalimab IV 240 mg/placebo + platinum-based doublet drug chemotherapy in 30 days after the operation. Then it will proceed to consolidation treatment period three weeks after adjuvant therapy; In the consolidation treatment period, Toripalimab IV 240 mg/placebo is given in each cycle of every 3 weeks for a total of 13 cycles . Adverse events (AEs) will be monitored throughout the study, and the severity will be graded to the guidelines listed in National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0 or above. The safety will be followed up in the subjects who have received study treatment and discontinued the drug prematurely. All the subjects will be followed up for overall survival, until death, withdrawal of informed consent or end of study ;