neoadjuvant pd-1 antibody plus chemotherapy in resectable stage iiia-n2 non-small-cell lung cancer

Conditions: Non Small Cell Lung Cancer

Summary: this is a randomized, open label study designed to evaluate the efficacy and safety of neoadjuvant pd-1 antibody plus chemotherapy followed by surgery in resectable stage iiia-n2 non-small cell lung cancer.

this is an open-label, randomised, two-arm, phase ii, multi-centre clinical trial. the proposed study will evaluate the efficacy and safety of preoperative administration pd-1 antibody plus chemotherapy in patients resectable stage iiia-n2 nsclc. data obtained in this study will provide valuable information for planning further phase iii clinical trials of anti-pd-1 and other immunotherapies in nsclc, both in the peri-operative and advanced disease setting.

Eligibility criteria:
inclusion criteria: * written informed consent provided. * males or females aged ≥18 years. * pathologically diagnosed of non-small cell lung cancer. * diagnosed as stage iiia- n2.the diagnosis standard of n2 is as below: pts with resectable stage iiia-n2 nsclc confirmed by mediastinoscopy or ebus and pet/ct. * tumor should be considered resectable before study entry by a multidisciplinary team. * ecog (performance status) 0-1. * screening laboratory values must meet the following criteria and should be obtained within 7 days prior to randomization. i. neutrophils ≥ 1500×109/l ii. platelets ≥ 100 x×109/l iii. hemoglobin \> 9.0 g/dl iv. serum creatinine ≤ 1.5 x uln or creatinine clearance (crcl) ≥ 40 ml/min v. ast/alt ≤ 3 x uln vi. total bilirubin ≤ 1.5 x uln (except subjects with gilbert syndrome, who can have total bilirubin \ 40% predicted value viii. inr/aptt within normal limits. * women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before randomization. * all sexually active men and women of childbearing potential must use an effective contraceptive method (two barrier methods or a barrier method plus a hormonal method) during the study treatment and for a period of at least 12 months following the last administration of trial drugs. * patient capable of proper therapeutic compliance and accessible for correct follow-up. * measurable or evaluable disease (according to recist 1.1 criteria). exclusion criteria: * all patients carrying activating mutations in the tk domain of egfr or any variety of alterations in the alk gene. * patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. * patients with a history of interstitial lung disease cannot be included if they have symptomatic ild (grade 3-4) and/or poor lung function. in case of doubt please contact trial team. * patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anti-cancer therapy. * patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period. * any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information. * patients who have had prior treatment with an anti-pd-1, anti-pd-l1, anti-pd-l2, anti-ctla-4 antibody, or any other antibody or drug specifically targeting t-cell costimulation or immune checkpoint pathways. * patients with positive test for hepatitis b virus surface antigen (hbv sag) or hepatitis c virus ribonucleic acid (hcv antibody) indicating acute or chronic infection. * patients with known history of testing positive for human immunodeficiency virus (hiv) or known acquired immunodeficiency syndrome (aids). * patients with history of allergy to study drug components excipients. * women who are pregnant or in the period of breastfeeding. * sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.