toripalimab plus pemetrexed+platinus in advanced non-small-cell lungcancer patients previsouly treated egfr-tki

Conditions: Non-small Cell Lung Cancer

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);


Eligibility criteria:
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