Phase II Concurrent Durvalumab and Radiotherapy for for Stage III Non-Small Cell Lung Cancer

Inclusion Criteria

1.1 Pathologically (histologically or cytologically) proven diagnosis of NSCLC with, medically inoperable (or patients who refuse resection) stage IIIA or stage IIIB disease (AJCC 8th edition);

1.1.1 Inoperable Stage IIIA disease is defined by multiple and/or bulky N2 mediastinal lymph nodes on computed tomography (CT) scan such that, in the opinion of the treating investigator, the patient was not a candidate for surgical resection.

1.1.2 N2 disease must have been documented by biopsy, or at a minimum by fluorodeoxyglucose positron emission tomography (PET) or CT if nodes were more than 2 cm in short axis diameter.

1.1.3 T4 disease is often considered resectable at the discretion of a thoracic surgeon. Patients with T4N0 or T4N1 disease can be enrolled if their case is reviewed by a thoracic surgeon and felt to be unresectable or if they are either medically inoperable or refuse surgery.

1.1.4 Stage IIIB patients have N3 or T4N2 status. N3 status must have been documented by the presence of a contralateral (to the primary tumor) mediastinal lymph node or supraclavicular or scalene lymph node proven by biopsy, or at a minimum by fluorodeoxyglucose uptake on PET or more than 2 cm in short axis diameter on CT scan. Patients with disease extending into the cervical region (defined as disease extending above cricoid cartilage) are not eligible.

1.2 Appropriate stage for study entry based on the following diagnostic workup:

1.2.1 History/physical examination, including documentation of height, weight and vital signs, within 30 days prior to registration;

1.2.2 CT scan with IV contrast (CT scan without contrast acceptable if IV contrast is medically contraindicated) of the lung and upper abdomen through the adrenal glands within 60 days prior to registration (recommended within 30 days prior to registration);

1.2.3 MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 60 days prior to registration; note: the use of intravenous contrast is required for the MRI or CT (unless medically contra-indicated).

1.2.4 Whole-body FDG-PET/CT within 60 days prior to registration;

1.3 Age ≥ 18 years;

1.4 Life expectancy ≥ 12 weeks

1.5 Zubrod Performance Status of 0-1 within 30 days prior to registration;

1.6 Adequate respiratory function within 180 days prior to registration defined as follows: FEV1 > 1.2 liters; DLCO ≥ 50% predicted;

1.7 Patients with post-obstructive pneumonia are eligible provided they no longer require intravenous antibiotics at registration;

1.8 Patients with a pleural effusion that is transudative, cytologically negative and non-bloody, are eligible if the radiation oncologist feels the tumor can be encompassed within a reasonable field of radiotherapy; if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging, the patient will be remain eligible.

1.9 Adequate organ and marrow function as defined below

1.9.1 Absolute neutrophil count >1.5 × 10^9/L

1.9.2 Platelet count >100 × 10^9/L

1.9.3 Baseline or post-transfusion Hemoglobin ≥9.0 g/dL

1.9.4 Serum bilirubin≤ 1.5x upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician.

1.9.5 Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x ULN.

1.9.6 Measured creatinine clearance (CL) >40 mL/min or calculated CL >40 mL/min as determined by Cockcroft-Gault (using actual body weight);

Males:

Creatinine CL = (Weight (kg) × (140 - Age)) / ((mL/min) 72 × serum creatinine (mg/dL))

Females:

Creatinine CL = (Weight (kg) × (140 - Age) × 0.85) / ((mL/min) 72 × serum creatinine (mg/dL))

1.10 Negative serum pregnancy test within three days prior to registration for women of childbearing potential.

1.11 Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier metho