Phase III Study of Toripalimab Versus Placebo Plus Chemotherapy in Resectable NSCLC
- Conditions
- Stage II-III Non-small Cell Lung Cancer
- Interventions
- Drug: 4cycles(Placebo + platinum-based doublet chemotherapy)+13 cycles(Placebo )
- Registration Number
- NCT04158440
- Lead Sponsor
- Shanghai Junshi Bioscience Co., Ltd.
- Brief Summary
This is a randomized, double-blind, placebo-controlled, multi-center, phase III clinical study to evaluate the efficacy and safety of Toripalimab injection (JS001) combined with platinum-based doublet drug chemotherapy versus placebo combined with platinum-based doublet drug chemotherapy for subjects with resectable, stage II-III NSCLC.
- Detailed Description
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
* Planned surgical operation: pneumonectomy vs. lobectomy
* Pathological type: non-squamous cell carcinoma vs. squamous cell carcinoma Neoadjuvant therapy should be started within 3 days after randomization. Toripalimab IV 240 mg Q3W /plaecbo will be given combined with platinum-based doublet drug chemotherapy for three cycles in the preoperative neoadjuvant therapy period for trial group; 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 3-5 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. If there is no adjuvant radiotherapy plan, it will proceed to consolidation treatment period three weeks after adjuvant therapy; if adjuvant radiotherapy is planned then the consolidation treatment period will start 30 days after adjuvant radiotherapy. 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 501
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 4cycles(Placebo + platinum-based doublet chemotherapy)+13 cycles(Placebo ) 4cycles(Placebo + platinum-based doublet chemotherapy)+13 cycles(Placebo ) Participants receive totally 4 cycles of Placebo combined with platinum doublet chemotherapy during perioperative period ;After surgery, participants receive consolidation therapy of Placebo
- Primary Outcome Measures
Name Time Method EFS in stage II-III population evaluated by investigators EFS: up to 3 years 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 in stage III population evaluated by investigators up to 3 years 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.
MPR rate in stage III population evaluated by BIPR up to 7 weeks after neoadjuvant 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.
MPR rate in stage II-III population evaluated by BIPR up to 7 weeks after neoadjuvant 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.
- Secondary Outcome Measures
Name Time Method pCR rate in stage III population evaluated by BIPR and investigators pCR:up to 7 weeks after neoadjuvant; 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.
Overall survival (OS) rate in stage III and II-III population OS up to 5 years OS is defined as the time from randomization until death from any cause.
Disease-free survival (DFS) in stage III evaluated by IRC and investigators DFS:up to 3 years DFS is defined as the time from postoperation until radiographic disease progression, local or distant recurrence, or death due to any cause.
EFS in stage II-III population evaluated by IRC EFS by IRC:up to 3 years 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 blinded central pathologist or by imaging using RECIST 1.1 assessed by investigator.
Disease-free survival (DFS) in stage II-III population evaluated by IRC and investigators DFS:up to 3 years DFS is defined as the time from postoperation until radiographic disease progression, , local or distant recurrence, or death due to any cause.
EFS in stage III population evaluated by IRC EFS by IRC:up to 3 years 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 blinded central pathologist or by imaging using RECIST 1.1 assessed by investigator.
pCR rate in stage II-III population evaluated by BIPR and investigators pCR:up to 7 weeks after neoadjuvant 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.
2-3 years overall survival (OS) rate in stage III and II-III population OS up to 5 years OS rate is defined as survival probability n stage III and II-III population at a given time point（2y，3y）
Trial Locations
- Locations (1)
Shanghai Chest Hospital
🇨🇳Shanghai, China