Neoadjuvant Durvalumab/Anlotinib /Chemotherapy Plus Curative Resection in Stage III Non-Small-Cell Lung Cancer : A Single-arm Phase II Study

Inclusion Criteria:

• Written informed consent provided.
• Males or females aged ≥18 years.
• Pathologically diagnosed of non-small cell lung cancer.
• Diagnosed as stage III.
• 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 obtainedwithin 7 days prior to treatment. 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 ≤ 3x ULN vi. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who canhave total bilirubin < 3.0 mg/dL) vii. The patients need to have a forced expiratoryvolume (FEV1) ≥ 1.2 liters or >40% predicted value viii. INR/APTT within normallimits.
• Women of childbearing potential, including women who had their last menstrual periodin the last 2 years, must have a negative serum or urine pregnancy test within 7 daysbefore randomization.
• All sexually active men and women of childbearing potential must use an effectivecontraceptive 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 lastadministration 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 ofalterations in the ALK gene.
• central type, with empty lung squamous cell carcinoma or non-small cell lung cancerwith hemoptysis (>50 mL/day).
• Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14days of randomization. Inhaled or topical steroids, and adrenal replacement steroiddoses > 10 mg daily prednisone equivalent, are permitted in the absence of activeautoimmune disease.
• Patients with a history of interstitial lung disease cannot be included if they havesymptomatic ILD (Grade 3-4) and/or poor lung function. In case of doubt please contacttrial team.
• Patients with other active malignancy requiring concurrent intervention and/orconcurrent treatment with other investigational drugs or anti-cancer therapy.
• Patients with previous malignancies (except non-melanoma skin cancers, and thefollowing in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia,melanoma, or breast) are excluded unless a complete remission was achieved at least 2years prior to study entry AND no additional therapy is required during the studyperiod.
• Any medical, mental or psychological condition which in the opinion of theinvestigator would not permit the patient to complete the study or understand thepatient 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-cellcostimulation or immune checkpoint pathways.
• Patients with positive test for hepatitis B virus surface antigen (HBV sAg) orhepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronicinfection.
• 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 arepregnant or in the period of breastfeeding.
• Sexually active men and women of childbearing potential who are not willing to use aneffective contraceptive method during the study.