Neoadjuvant PD-1 Antibody Plus Chemotherapy in Resectable Stage IIIA-N2 Non-Small-Cell Lung Cancer

Neoadjuvant PD-1 Antibody Plus Chemotherapy in Resectable Stage IIIA-N2 Non-Small-Cell Lung Cancer: A Randomized Phase II Study

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.

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 < 3.0 mg/dL) vii. The patients need to have a forced expiratory volume (FEV1) ≥ 1.2 liters or >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.