Study of Nivolumab for Non-Small Cell Lung Cancer (Stage III) Following Neoadjuvant Chemotherapy Plus Nivolumab and Definitive Concurrent Chemoradiation Therapy

Concurrent enrolment in another clinical study, unless it is an observational(non-interventional) clinical study;

Mixed small cell and non-small cell lung cancer histology;

Current or prior use of immunosuppressive medication within 28 days before the first dose of Nivolumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.

Prior exposure to any anti-programmed cell death protein(PD)-1 or anti-PD-L1 antibody;

Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of nivolumab;

Active or prior documented autoimmune disease within the past 2 years;

Active or prior documented inflammatory bowel disease (eg. Crohn's disease, ulcerative colitis);

History of primary immunodeficiency;

History of organ transplant that requires therapeutic immunosuppression;

Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from3 electrocardiograms (ECGs) using Bazett's Correction;

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent;

Known history of tuberculosis;

Receipt of live attenuated vaccination within 30 days prior to study entry or within30 days of receiving nivolumab;

History of another primary malignancy within 5 years prior to starting nivolumab, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study;

Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control;

Any condition that, in the opinion of the investigator, would interfere with evaluation of the nivolumab or interpretation of patient safety or study results.

Patients who develop distant metastasis;

Patients who develop locoregional disease progression and the irradiation dose of normal tissue will exceed the limit as defined in Section 7.

World Health Organization (WHO) Performance Status of 2-4;

Inadequate organ and marrow function as defined below:

* Forced expiratory volume in 1 second (FEV1) \<800ml

* Absolute neutrophil count \<1.5 x 109/L (1500 per mm3)

* Platelets \<100 x 109/L (100,000 per mm3)

* Haemoglobin\<9.0 g/dL (5.59 mmol/L)

* Serum creatinine CL \<50 mL/min by the Cockcroft-Gault formula (Cockcroft and

Gault 1976)

* Serum bilirubin \>1.5 x upper limit of normal (ULN).

* Aspartate Transaminase(AST) and Alanine Transaminase(ALT) \>2.5 x ULN

Patients who have progressed whilst definitive platinum based, concurrent chemoradiation therapy;

Current or prior use of immunosuppressive medication within 28 days before the first dose of Nivolumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.

Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy will be excluded from randomization;

Patients with Grade ≥2 pneumonitis from prior chemoradiation therapy will be excluded from randomization; Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE\>Grade 1.

What this study is about