Description:
This is a randomized, double-blind, placebo-controlled, multi-center, phase III trial to
evaluate the efficacy and safety of Toripalimab injection (JS001) combined with
platinum-based doublet chemotherapy versus placebo combined with platinum-based doublet
chemotherapy in resectable stage IIIA NSCLC.
Subjects meet all the inclusion and exclusion criteria will be paralleled assigned according
to the stratification factors as below :
- Pathological type: squamous cell carcinoma vs. non-squamous cell carcinoma
- PD-L1 status: PD-L1 expression ≥1% vs. PD-L1<1% or not evaluable
- Planned surgical operation:pneumonectomy vs. lobectomy Neoadjuvant therapy should be
started within 3 days after randomization. , Toripalimab IV 240mg Q3W will be given
combined with platinum-based doublet chemotherapy for three cycles in the neoadjuvant
setting in the experimental group; Every 3 weeks of treatment is regarded as one cycle,
in which combined therapy is given in the first day of every cycle. Placebo combined
with platinum-based doublet chemotherapy will be given for three cycles in the control
group instead..
All the subjects will receive preoperative radiological and surgical evaluation 3-5 weeks
afterneoadjuvant therapy..
,All the qualified subjects will receive radical excison based on the surgical operation
criteria of the World Association for Lung Cancer Research within 4-6 weeks after neoadjuvant
therapy. Pathologic staging based on AJCC Cancer Staging Manual (version 8) of the whole
specimens will be performed by the local pathologist. And then all the specimens will be sent
to the BIPR for further evaluation.. All the subjects accept the radical operation will
receive one cycle of postoperative neoadjuvant therapy, i.e., Toripalimab IV 240mg / placebo
+ platinum-based doublet chemotherapy, 30 days after the operation. In case of no indication
for radiotherapy, it will proceed to consolidation treatment period three weeks later; if
indicated for radiotherapy, it will proceed to consolidation treatment period 30 days after
theradiotherapy. In the consolidation treatment setting , JS001 is given byIV 240mg in each
cycle of every 3 weeks for a total of 13 cycles i in the experimental group; placebo is given
by IV 240mg in each cycle of every 3 weeks for a total of 13 cycles in the control group.
Adverse events (AE) will be monitored throughout the study, and the seriousness will be
graded tothe guideline 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 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.
Title
- Brief Title: Study of Toripalimab or Placebo Plus Chemotherapy as Treatment in Early Stage NSCLC
- Official Title: A Randomized,Double-blinded, Multi-center Phase III Study of Toripalimab or Placebo Plus Chemotherapy as Treatment in Early Stage Non-Small Cell Lung Cancer
Clinical Trial IDs
- ORG STUDY ID:
JS001-029-III-NSCLC
- NCT ID:
NCT04158440
Conditions
- Stage IIIA Non-small Cell Lung Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| 4cycles(Toripalimab IV 240mg + platinum-based doublet chemotherapy)+13 cycles(Toripalimab IV 240mg); Biological: Toripalimab | Cisplatin;, Carboplatin;, Pemetrexed;, Paclitaxel;, Docetaxel | 4cycles Toripalimab+platinum doublet chemotherapy,13 cycles Toripalimab Neoadjuvant Chemotherapy |
| 4cycles(Placebo + platinum-based doublet chemotherapy)+13 cycles(Placebo ) | Cisplatin;, Carboplatin;, Pemetrexed;, Paclitaxel;, Docetaxel | 4cycles(Placebo + platinum-based doublet chemotherapy)+13 cycles(Placebo ); Neoadjuvant Chemotherapy |
Purpose
This is a randomized, double-blind, placebo-controlled, multi-center, phase III trial to
evaluate the efficacy and safety of Toripalimab injection (JS001) combined with
platinum-based doublet chemotherapy versus placebo combined with platinum-based doublet
chemotherapy in resectable stage IIIA NSCLC.
Subjects meet all the inclusion and exclusion criteria will be paralleled assigned according
to the stratification factors as below :
- Pathological type: squamous cell carcinoma vs. non-squamous cell carcinoma
- PD-L1 status: PD-L1 expression ≥1% vs. PD-L1<1% or not evaluable
- Planned surgical operation:pneumonectomy vs. lobectomy Neoadjuvant therapy should be
started within 3 days after randomization. , Toripalimab IV 240mg Q3W will be given
combined with platinum-based doublet chemotherapy for three cycles in the neoadjuvant
setting in the experimental group; Every 3 weeks of treatment is regarded as one cycle,
in which combined therapy is given in the first day of every cycle. Placebo combined
with platinum-based doublet chemotherapy will be given for three cycles in the control
group instead..
All the subjects will receive preoperative radiological and surgical evaluation 3-5 weeks
afterneoadjuvant therapy..
,All the qualified subjects will receive radical excison based on the surgical operation
criteria of the World Association for Lung Cancer Research within 4-6 weeks after neoadjuvant
therapy. Pathologic staging based on AJCC Cancer Staging Manual (version 8) of the whole
specimens will be performed by the local pathologist. And then all the specimens will be sent
to the BIPR for further evaluation.. All the subjects accept the radical operation will
receive one cycle of postoperative neoadjuvant therapy, i.e., Toripalimab IV 240mg / placebo
+ platinum-based doublet chemotherapy, 30 days after the operation. In case of no indication
for radiotherapy, it will proceed to consolidation treatment period three weeks later; if
indicated for radiotherapy, it will proceed to consolidation treatment period 30 days after
theradiotherapy. In the consolidation treatment setting , JS001 is given byIV 240mg in each
cycle of every 3 weeks for a total of 13 cycles i in the experimental group; placebo is given
by IV 240mg in each cycle of every 3 weeks for a total of 13 cycles in the control group.
Adverse events (AE) will be monitored throughout the study, and the seriousness will be
graded tothe guideline 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 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 4cycles Toripalimab+platinum doublet chemotherapy,13 cycles Toripalimab Neoadjuvant Chemotherapy | Experimental | Participants receive totally 4 cycles of Toripalimab combined with platinum doublet chemotherapy during peioperative period ;After surgery, participants receive consolidation therapy of Toripalimab | - 4cycles(Toripalimab IV 240mg + platinum-based doublet chemotherapy)+13 cycles(Toripalimab IV 240mg); Biological: Toripalimab
|
| 4cycles(Placebo + platinum-based doublet chemotherapy)+13 cycles(Placebo ); Neoadjuvant Chemotherapy | Experimental | Participants receive totally 4 cycles of Placebo combined with platinum doublet chemotherapy during peioperative period ;After surgery, participants receive consolidation therapy of Toripalimab | - 4cycles(Placebo + platinum-based doublet chemotherapy)+13 cycles(Placebo )
|
Eligibility Criteria
Inclusion criteria:
1. Having sufficient understanding of this study and being willing to sign the informed
consent form (ICF);
2. Age 18-70 years, male or female;
3. Treatment-naive, histologically confirmed, resectable stage IIIA (AJCC staging system
version 8) NSCLC;
4. Measurable lesion based on the response evaluation criteria in solid tumors version
1.1;
5. Being will to provide specimens or related pathological report for the biomarkers
evaluation prior to the randomization.
6. ECOG score 0-1;
7. Good organ function:
8. Being willing and able to comply with visits, treatment plan, laboratory examinations
and other study procedures scheduled .
9. Total lung capacity is able to withstand the planned pneumonectomy evaluated by
surgeons;
10. Women of childbearing potential must undergo serum pregnancy test within 3 hours prior
to the first dose and the result must be negative. Female subjects of childbearing
potential and male subjects whose partners are women of childbearing potential must
agree to use highly effective contraceptive methods during the study period and within
180 days after the last dose of study drug.
Exclusion criteria:
1. Locally advanced, unresectable or metastatic disease.
2. NSCLC involving superior sulcus, large cell neuroendocrine carcinoma (LCNEC),
sarcomatoid tumor.
3. Participants with known EGFR mutation or ALKfusion .
4. Early NSCLC previously treated with systemic antitumor therapy, including
investigational product.
5. History or current evidence of any disease, therapy or abnormal laboratory examination
that may confound the study results, interfere with subject's participation in the
whole study or not meet the best interest of subject's participation in the study, as
judged by investigators.
| Maximum Eligible Age: | 70 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Major Pathological Response by BIPR |
| Time Frame: | MPR:up to 7 weeks after neoadjuvant |
| Safety Issue: | |
| Description: | 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 |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Shanghai Junshi Bioscience Co., Ltd. |
Last Updated
March 17, 2021
