toripalimab as maintenance therapy in patients with driver-gene negative advanced nsclc after first-line chemotherapy

Conditions: NSCLC Stage IV

Summary: lung cancer is the malignant tumor with the highest incidence and mortality in china. non-small cell lung cancer (nsclc) ,which includes non-squamous cell carcinoma (including adenocarcinoma, large cell carcinoma, and other cell types) and squamous cell carcinoma, accounts for about 80% of lung cancer. platinum-based two-drug chemotherapy is the first-line standard treatment for driver-gene negative advanced nsclc, but most patients experience disease progression after 4 to 6 months. to extend the efficacy of first-line treatment, maintenance therapy is a logical clinical option for patients who are effective after 4 to 6 cycles of standard treatment. there is currently no standard regimen for maintenance treatment of nsclc. we evaluated the effectiveness and safety of maintenance therapy with the anti-pd-1 monoclonal antibody (toripalimab injection) followed by the first-line standard regimen in advanced nsclc patients who are effective after standard treatment. with a view to exploring treatment methods that are effective for the maintenance treatment of driver-gene negative advanced nsclc and have little toxic and side effects,thereby improving the survival prognosis of these patients.

platinum-based two-drug chemotherapy is the first-line standard treatment for driver-negative advanced nsclc, but most patients experience disease progression after 4 to 6 months. to extend the efficacy of first-line treatment, maintenance therapy is a logical clinical option for patients who are effective after 4 to 6 cycles of standard treatment. there is currently no standard regimen for maintenance treatment of nsclc. we evaluated the effectiveness and safety of the anti-pd-1 monoclonal antibody (toripalimab injection) followed by maintenance therapy in advanced nsclc that was effective in the first-line standard regimen.thereby improving the survival prognosis of advanced nsclc.

Eligibility criteria:
criteria: inclusion criteria: * fully understand the research and voluntarily sign the informed consent form (icf) * age 18 to 75 years * histological or cytological documentation of non-small cell lung cance. * diagnosed as stage iv by imaging (staging according to ajcc eighth edition). * gene test is negative for egfr, alk, ros1 confirmed by molecular pathology (tissue, arms method or ngs). * previously received first-line standard chemotherapy for non-small cell lung cancer (platinum combined with third-generation chemotherapy drugs in a two-drug combination regimen: pemetrexed or paclitaxel or docetaxel or gemcitabine or vinorelbine combined with cisplatin or carboplatin), and which were assessed the effectiveness by imaging(sd, pr or cr). * at least one measurable lesion according to response evaluation criteria in solid tumors (recist) criteria measured within 4 weeks prior to registration. * ecog performance status 0-1 * expected overall survival time≥3 months * adequate bone marrow, coagulation function，hepatic and renal function should be assessed by the following laboratory requirements conducted within 7 days before starting study treatment: * leukocytes ≥ 3.0 x109/ l, absolute neutrophil count (anc) ≥ 1.5 x109/ l, platelet count ≥ 100 x109/ l, hemoglobin (hb) ≥9g/ dl. * total bilirubin ≤ 1.5 x the upper limit of normal (uln). * alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤ 2.5 x uln. * serum creatinine ≤ 1.5 x the uln. * calculated creatinine clearance or 24 hour creatinine clearance ≥ 40 ml/ min. * inr≤1.5, activated partial thromboplastin time(aptt)≤1.5×uln. * patients with hepatitis b virus (hbv) infection and inactive/asymptomatic hbv carriers, or patients with chronic or active hbv, if the hbv dna is \<500iu/ml, or 2500copies/ml at the time of screening,can enter the group. * male subjects and women of childbearing age must have contraception within 24 weeks from the start of the study to the last time of using the drug. exclusion criteria: * tumor histology or cytology pathology confirmed with small cell lung cancer components or sarcomatoid lesions. * previously received any t-cell co-stimulation or immune checkpoint therapy, including but not limited to ctla-4 inhibitors, pd-1 inhibitors, pd-l1 / 2 inhibitors or other drugs that target t cells. * major autoimmune diseases. * subjects who were vaccinated or planned to be vaccinated within 4 weeks before the first time using the study drug. * ld, drug-induced pneumonia, radiation pneumonitis requiring steroid therapy, or clinically active pneumonia or severe pulmonary dysfunction. * tb or subjects with a history of active tuberculosis infection ≤ 48 weeks before screening, whether or not treated. * symptomatic cardiac disease, such as: heart failure above nyha level 2, unstable angina pectoris, myocardial infarction occurred within 24 weeks, clinically significant supraventricular or ventricular arrhythmias require treatment or intervention. * acquired immunosuppression (aids or major immunosuppressive agents) * suffering from active viral hepatitis. defined as: hepatitis b virus (hbv) infection and hbv dna ≥ 2500 copies / ml; or hepatitis c virus (hcv) infection (quantitative test results of anti-hcv positive and hcv rna are greater than the lower limit of detection) . * mental illness, alcohol, drug or substance abuse * pregnant or lactating women.

Keywords: driver-gene negative advanced nsclc maintenance treatment