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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
478
SBRT. 24Gy/3fractions Toripalimab 240 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1;Drug: Cisplatin 75 mg/m\^2 by IV infusion Q3W, given on cycle day 1;Drug: Corboplatin AUC 5 by IV infusion Q3W, given on cycle day 1;Drug: Pemetrexed 500 mg/m\^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.Drug:Paclitaxel 175 mg/m\^2 by IV infusion Q3W;Drug:Docetaxel 60-75 mg/m\^2 by IV infusion Q3W
Toripalimab 240 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1;Drug: Cisplatin 75 mg/m\^2 by IV infusion Q3W, given on cycle day 1;Drug: Corboplatin AUC 5 by IV infusion Q3W, given on cycle day 1;Drug: Pemetrexed 500 mg/m\^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.Drug:Paclitaxel 175 mg/m\^2 by IV infusion Q3W;Drug:Docetaxel 60-75 mg/m\^2 by IV infusion Q3W
Shanghai Chest Hospital
Shanghai, China
RECRUITING2-year Event Free Survival Rate
Event Free Survival (EFS):EFS is defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. EFS determined either by biopsy assessed by central pathologist or by imaging using RECIST 1.1 assessed by BICR.
Time frame: 2 years
pCR rate
Pathological Complete Response (pCR) Rate :pCR rate is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes following completion of neoadjuvant therapy.
Time frame: up to 7 weeks after neoadjuvant
Major Pathological Response
Major Pathological Response (mPR) Rate.mPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes in neoadjuvant therapy
Time frame: up to 7 weeks after neoadjuvant
Lymph node downstaging rate
Time frame: up to 7 weeks after neoadjuvant
Perioperative complications
Time frame: 90 days after the last administration
Treatment associated adverse events
Adverse event (AE), abnormal laboratory examination, serious adverse event (SAE) related with the study drug judged using NCI-CTCAE V5.0; surgical feasibility: percentage of procedure delay or cancellation, change of surgical approach, operation time
Time frame: 90 days after the last administration
EFS
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
EFS is defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. EFS determined either by biopsy assessed by central pathologist or by imaging using RECIST 1.1 assessed by investigator
Time frame: up to 3 years
Disease-free survival (DFS)
DFS is defined as the time from postoperation until radiographic disease progression, , local or distant recurrence, or death due to any cause
Time frame: up to 3 years
Overall survival (OS)
OS is defined as the time from randomization until death from any cause.
Time frame: up to 3 years
R0 resection rate
Time frame: up to 7 weeks after neoadjuvant
Surgical Completion Rate
Time frame: up to 7 weeks after neoadjuvant