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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Treatment-naive Advanced Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: TORIPALIMAB INJECTION (JS001 ) combine with chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Only the patients meeting all the following criteria can be eligible to participate in the trial: Histologically and/or cytologically confirmed stage IV non-small cell lung cancer and ALK fusion 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: Known allergy to recombinant humanized anti-PD-1 monoclonal antibody drug and its components; Histologically or cytopathologically confirmed combination with small cell lung cancer component or sarcomatoid lesion; Current participation in and receiving other study treatment, or participation in treatment of one study drug within 4 weeks prior to administration of JS001; Previous use of systematic chemotherapy for advanced NSCLC; targeted therapy for advanced NSCLC 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); Chest (lung) radiotherapy > 30 Gy within 6 months prior to the start of study treatment. Active tuberculosis (TB), receiving anti-tuberculosis therapy currently or within one year prior to screening; Known active central nervous system (CNS) metastasis and/or cancerous meningitis; 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 Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage Uncontrollable or symptomatic hypercalcemia Clinically uncontrolled active infection, including but not limited to acute pneumonia; Uncontrollable major epileptic seizure or superior vena cava syndrome Previous or current combination with other malignancies ; 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; Known hepatic diseases of clinical significance, including active viral hepatitis, alcoholic hepatitis or other hepatitis, liver cirrhosis, fatty liver, hereditary liver disease; Use of systemic immunosuppressive therapy for any active autoimmune disease within two years prior to Day 1 of the 1st cycle; Vaccination of live-virus vaccine within 30 days after the start of planned treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group TORIPALIMAB combined with standard chemotherapy<br> | Drug: TORIPALIMAB INJECTION (JS001 ) combine with chemotherapy<br>* TORIPALIMAB INJECTION(JS001 ) or Placebo ,240mg/6ml/vial, Q3W,up to 2 years of treatment.<br>* Other names: JS001, TAB001;|
| Placebo Comparator: Group Placebo combined with standard chemotherapy<br> | Drug: TORIPALIMAB INJECTION (JS001 ) combine with chemotherapy<br>* TORIPALIMAB INJECTION(JS001 ) or Placebo ,240mg/6ml/vial, Q3W,up to 2 years of treatment.<br>* Other names: JS001, TAB001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression free survival (PFS) evaluated by investigators according to the response evaluation criteria in solid tumors (RECIST 1.1) | Up to 2 approximately years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall survival (OS) | Up to 2 approximately years | 
| PFS | PFS evaluated by the Blinded Individual Review Committee (BIRC) based on RECIST1.1 criteria | Up to 2 approximately years | 
| ORR | Objective response rate (ORR) evaluated by investigators and BIRC based on RECIST1.1 | Up to 2 approximately years | 
| DOR | Duration of response (DOR) evaluated by investigators and BIRC based on RECIST1.1 | Up to 2 approximately years | 
| DCR | Disease control rate (DCR) evaluated by investigators and BIRC based on RECIST1.1 | Up to 2 approximately years | 
| TTR | Time to response (TTR) evaluated by investigators and BIRC based on RECIST1.1 | Up to 2 approximately years | 
| Incidence of AEs/SAEs | Overall incidence of adverse events (AEs); incidence of grade 3 and above AEs; incidence of serious adverse events (SAEs); incidence of AEs leading to termination of the investigational drug; incidence of AEs interruption of the investigational drug | From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years |