Toripalimab Plus Pemetrexed+Platinus in Advanced Non-small-cell Lungcancer Patients Previsouly Treated EGFR-TKI
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03924050
- Lead Sponsor
- Shanghai Junshi Bioscience Co., Ltd.
- 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);
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 440
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 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group Placebo combined with standard chemotherapy TORIPALIMAB INJECTION(JS001 ) - Group TORIPALIMAB combined with standard chemotherapy TORIPALIMAB INJECTION(JS001 ) -
- Primary Outcome Measures
Name Time Method OS Approximately 5 years Overall survival，It's suitable for all subjects.
- Secondary Outcome Measures
Name Time Method 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)
TTR (Time to Response) Approximately 4 years Time to response (TTR) evaluated by investigators based on RECIST1.1;
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;
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
Trial Locations
- Locations (2)
Shanghai Pulmonary Hospital
🇨🇳Shanghai, Shanghai, China
Peking University Shenzhen Hospital
🇨🇳Shenzhen, China