Non-small Cell Lung Cancer
Conditions
Brief summary
This is a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study to evaluate the efficacy and safety of Toripalimab injection (JS001) or placebo combined with chemotherapy in Advanced Non-small Cell Lung Cancer (NSCLC) Participants with TKI-resistant EGFR-mutated Tumors; and evaluate the population with the best predictive biomarkers, i.e., positive diagnosis population. About 440 subjects with advanced non-small cell lung cancer with activated EGFR mutation will be 1:1 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: The history of the previous lines of EGFR-TKI treament ( 1st or 2nd generation of TKI vs. 3rd generation of TKI vs. 1st or 2nd generation of TKI + 3rd generation of TKI) ; Disease stage (IIIB-C vs. IV);
Interventions
TORIPALIMAB INJECTION(JS001 ) or Placebo, 240mg/6ml/vial, Q3W,up to 2 years of treatment.
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Only the patients meeting all the following criteria can be eligible to participate in the trial: * Fully informed consent and signed ICF; * Age of 18-75 years; * Histologically and/or cytologically confirmed advanced or recurrent stage III B-C or IV (AJCC Version 8) NSCLC with TKI-resistant EGFR-mutated tumors, which also satisfy following conditions: Without T790M mutation in exon 20 after 1st or 2nd generation EGFR-TKI (eg, gefitinib, erlotinib, icotinib, afatinib,etc.) treatment failure;If with T790M mutation in exon 20 after 1st or 2nd generation EGFR-TKI (eg, gefitinib, erlotinib, icotinib, afatinib,etc.),participants are required to have osimertinib or other 3rd generation EGFR-TKI treatment failure prior to enrollment.Participants with osimertinib treatment failure as 1st line therapy (regardless of their EGFR T790M mutation status);Previous neoadjuvant/adjuvant chemotherapy is allowed, but the time interval between the last dose of chemotherapy and recurrence/metastasis must be at least 6 months. * With at least one measurable disease per RECIST 1.1; * Agree to provide formalin fixed tumor specimen after EGFR-TKI treatment failure or provide fresh biopsy tissue; * ECOG performance status of 0-1; * Life expectancy ≥ 3 months; * Good organ function; * Any adverse event resulting from prior treatment, surgery, or radiotherapy must return to grade 0 or 1 according to NCI-CTCAE v5.0, except for alopecia of any grade; * Willing and able to follow protocol visits, treatment plans, laboratory tests and other study procedures; * Women of childbearing potential must have negative serum pregnancy test within 3 days prior to the first dose of investigational product:
Exclusion criteria
* Exclusion of tumor histology or cytology confirmed the presence of small cell lung cancer components, or squamous cell carcinoma components of more than 10%; * Combined with other driver mutations with known therapeutic drug, including but not limited to: ALK rearrangement, ROS1 mutation, BRAF600E mutation; * Previous systematic chemotherapy for advanced NSCLC; * Subjects with no measurable lesions; * Subjects with cancer meningitis and spinal cord compression; * Subjects with untreated central nervous system (CNS) tumor metastasis; * Subjects were previously treated with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 agent; * Subjects with any active, known or suspected autoimmune disease; * Subjects who are now participating in other clinical studies or the last dose of prior investigational drug was given in \< 4 weeks (or 5 half-lives) from the first investigational product administration of this study; * Subjects who were expected to receive any other antitumor therapy (eg, other maintenance therapy for NSCLC, radiotherapy, and/or surgical excision); * Subjects who received major surgery within 4 weeks prior to enrollment or were not fully recovered from prior surgery; * Subjects with other malignancies requiring concurrent treatment; * Subjects with grade II or above myocardial ischemia or myocardial infarction, or subjects with arrhythmia with poor control; * Subjects with uncontrolled pleural/pericardial effusion, or with ascites requiring repeated drainage; * Subjects with uncontrolled tumor-related pain; * Subjects with severe allergic reactions to other monoclonal antibodies and subjects with severe allergic reactions to pemetrexed, platinum or its prophylaxis; * Subjects with psychological disorder, alcohol alcoholism, drug abuse or drug dependency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| OS | Approximately 5 years | Overall survival，It's suitable for all subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS (Progression Free Survival) by investigator | Approximately 4 years | Progression free survival (PFS) evaluated by investigators according to the response evaluation criteria in solid tumors (RECIST 1.1) |
| ORR (Objective Response Rate) | Approximately 4 years | Objective response rate (ORR) evaluated by investigators based on RECIST1.1; |
| DOR (Duration of Response) | Approximately 4 years | Duration of response (DOR) evaluated by investigators and BIRC based on RECIST1.1; |
| DCR (Disease of Response) | Approximately 4 years | Disease control rate (DCR) evaluated by investigators based on RECIST1.1; |
| TTR (Time to Response) | Approximately 4 years | Time to response (TTR) evaluated by investigators based on RECIST1.1; |
| Incidence of AEs/SAEs | Approximately 5 years | Adverse events (AEs) study drug related; serious adverse events (SAEs)study drug related; abnormal value of Lab test according to NCI-CTCAE V5.0 |
Countries
China
Outcome results
None listed