A Study to Evaluate the Efficacy and Safety of Toripalimab or Placebo Combined With Chemotherapy in Treatment-naive Advanced NSCLC

A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Study to Evaluate the Efficacy and Safety of Toripalimab Injection (JS001) or Placebo Combined With First-line Standard Chemotherapy in Treatment-naive Advanced Non-small Cell Lung Cancer (NSCLC)

This is one randomized, double-blind, placebo-controlled, multi-center, phase III clinical study to evaluate the efficacy and safety of Toripalimab injection (JS001) or placebo combined with standard 1st-line chemotherapy in treatment-naïve advanced non-small cell lung cancer (NSCLC); and evaluate the population with the best predictive biomarkers, i.e., positive diagnosis population.

About 450 subjects with advanced non-small cell lung cancer without activated EGFR mutation (exon 19 deletion, or exon 21 L858R, exon 21 L861Q, exon 18 G719X or exon 20 S768I mutations) and ALK fusion will be 2:1 randomized into two groups, JS001 combined with the standard 1st-line chemotherapy will be given in the study group whereas placebo combined with standard 1st-line chemotherapy will be given in the control group. The stratification will be based on the following factors:

PD-L1 expression (TC≥1% vs TC<1%); Smoking state (often smoking vs no smoking or infrequent smoking); Pathological type (squamous cell carcinoma vs non-squamous cell carcinoma).

Inclusion Criteria:

Only the patients meeting all the following criteria can be eligible to participate in the trial:

1. Histologically and/or cytologically confirmed stage IV non-small cell lung cancer and ALK fusion
2. At least one measurable lesion 3 No history of any systemic anti-tumor therapy.

4. Agreement on providing formalin fixed tumor tissue specimen or fresh biopsy tissue from tumor lesions after diagnosis of metastasis 6. Age of 18-75 years 7. ECOG Scores 0-1; 8. Expected survival ≥ 3 months;

Exclusion Criteria:

1. Known allergy to recombinant humanized anti-PD-1 monoclonal antibody drug and its components;
2. Histologically or cytopathologically confirmed combination with small cell lung cancer component or sarcomatoid lesion;
3. Current participation in and receiving other study treatment, or participation in treatment of one study drug within 4 weeks prior to administration of JS001;
4. Previous use of systematic chemotherapy for advanced NSCLC; targeted therapy for advanced NSCLC
5. Previous use of anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cells synergetic stimulation or checkpoint pathway, such as IDO, IL-2R, GITR);
6. Chest (lung) radiotherapy > 30 Gy within 6 months prior to the start of study treatment.
7. Active tuberculosis (TB), receiving anti-tuberculosis therapy currently or within one year prior to screening;
8. Known active central nervous system (CNS) metastasis and/or cancerous meningitis;
9. Spinal cord compression for which operation and/or radical radiotherapy has not been given, or no clinical evidence of stable disease for ≥4 weeks prior to enrollment after treatment for previously diagnosed spinal cord compression
10. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage
11. Uncontrollable or symptomatic hypercalcemia
12. Clinically uncontrolled active infection, including but not limited to acute pneumonia;
13. Uncontrollable major epileptic seizure or superior vena cava syndrome
14. Previous or current combination with other malignancies ;
15. History of idiopathic pulmonary fibrosis, organized pneumonia (e.g., obliterating bronchiolitis), drug induced pneumonia, idiopathic pneumonia or evidence of active pneumonia during chest CT scanning for screening;
16. Known hepatic diseases of clinical significance, including active viral hepatitis, alcoholic hepatitis or other hepatitis, liver cirrhosis, fatty liver, hereditary liver disease;
17. Use of systemic immunosuppressive therapy for any active autoimmune disease within two years prior to Day 1 of the 1st cycle;
18. Vaccination of live-virus vaccine within 30 days after the start of planned treatment