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).

Study Overview

• Status: Completed
• Conditions: Treatment-naive Advanced Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: TORIPALIMAB INJECTION (JS001 ) combine with chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 465
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group TORIPALIMAB combined with standard chemotherapy	Drug: TORIPALIMAB INJECTION (JS001 ) combine with chemotherapy; TORIPALIMAB INJECTION(JS001 ) or Placebo ,240mg/6ml/vial, Q3W,up to 2 years of treatment.; Other Names: JS001, TAB001
PLACEBO_COMPARATOR: Group Placebo combined with standard chemotherapy	Drug: TORIPALIMAB INJECTION (JS001 ) combine with chemotherapy; TORIPALIMAB INJECTION(JS001 ) or Placebo ,240mg/6ml/vial, Q3W,up to 2 years of treatment.; Other Names: JS001, TAB001

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Publications and helpful links

General Publications

• Wang Z, Wu L, Li B, Cheng Y, Li X, Wang X, Han L, Wu X, Fan Y, Yu Y, Lv D, Shi J, Huang J, Zhou S, Han B, Sun G, Guo Q, Ji Y, Zhu X, Hu S, Zhang W, Wang Q, Jia Y, Wang Z, Song Y, Wu J, Shi M, Li X, Han Z, Liu Y, Yu Z, Liu AW, Wang X, Zhou C, Zhong D, Miao L, Zhang Z, Zhao H, Yang J, Wang D, Wang Y, Li Q, Zhang X, Ji M, Yang Z, Cui J, Gao B, Wang B, Liu H, Nie L, He M, Jin S, Gu W, Shu Y, Zhou T, Feng J, Yang X, Huang C, Zhu B, Yao Y, Tang X, Yu J, Maher E, Feng H, Yao S, Keegan P, Wang J. Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non-Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01). J Clin Oncol. 2023 Jan 20;41(3):651-663. doi: 10.1200/JCO.22.00727. Epub 2022 Oct 7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 18, 2019
• Primary Completion (ACTUAL): August 31, 2022
• Study Completion (ACTUAL): January 9, 2023

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: February 25, 2019
• First Posted (ACTUAL): February 27, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2023
• Last Update Submitted That Met QC Criteria: January 31, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: JS001-019-III-NSCLC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No