Oncolytic Adenovirus-Mediated Gene Therapy for Lung Cancer

Inclusion Criteria: * Pathologically (histologically or cytologically) proven diagnosis of NSCLC. * Clinical stage I/IIA (T1a - T2b; AJCC Staging 7th edition) with a tumor size \> 1 cm to ≤ 6 cm in diameter (long axis) based on the following minimum diagnostic workup: Note: Subjects may have M0 or MX status (e.g., lung nodules that are being observed). Known M1 disease is excluded. Subjects may have only one target lesion for SBRT. * Evaluation at lung multi-disciplinary tumor board with recommendation for SBRT within 12 weeks of registration. * Whole body positron emission tomography (PET/CT) scan within 12 weeks of registration using \[18F\]-FDG with adequate visualization of the primary tumor and draining lymph node basins in the hilar and mediastinal regions. Mediastinal lymph node sampling by any technique is allowed but not required. Subjects with \> 1.5 cm mediastinal lymph nodes on CT or abnormal PET (including suspicious but non-diagnostic uptake) may still be eligible if directed tissue biopsies of abnormally identified areas are negative for cancer. * Zubrod Performance Status 0 - 2 with 4 weeks of registration. * Age ≥ 18. * Subjects must have adequate baseline organ function, as assessed by the following laboratory values, within 30 days before initiating the study therapy: * Adequate renal function with serum creatinine ≤ 1.5 mg/dL or creatinine clearance \>50 mL/min/m2. * Platelet count \> 100,000/μL. * Absolute neutrophil count \> 1,000/μL. * Hemoglobin \> 10.0 g/dL. * Bilirubin \> 1.5 mg/dL * AST/SGOT and ALT/SGPT \< 3.0 times upper limit of normal (ULN). * Negative serum or urine pregnancy test within 72 hours prior to the adenovirus injection for women of childbearing potential. * Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout and for 60 days beyond the treatment phase of the study. * Subjects must possess the ability to give informed consent and express a willingness to meet all of the expected requirements of the protocol for the duration of the study. Exclusion Criteria: * Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (e.g., carcinomas in situ of the breast, oral cavity, or cervix are permissible). Subjects with previous lung cancer are permitted if the subject is disease-free for a minimum of 2 years or if this is a solitary recurrence in the lung measuring \> 2 cm and ≤ 5 cm after surgery. * Any known metastatic disease. Subjects may have MX status (e.g., lung nodules that are being observed). * Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields. * Prior chemotherapy for the study cancer. * Plans for the subject to receive other local therapy (including standard fractionated radiotherapy and/or surgery and/or other local ablative therapies) while on this study, except in the case of disease progression. * Plans for the subject to receive systemic therapy (including standard chemotherapy or biologic targeted agents), while on this study, except in the case of disease progression. * Acute infection. Acute infection is defined by any viral, bacterial, or fungal infection that requires specific therapy within 72 hours of initiation of the study therapy. * Previous history of liver disease including hepatitis. * Immunosuppressive therapy including systemic corticosteroids. Use of inhaled and topical corticosteroids is permitted. * Impaired immunity or susceptibility to serious viral infections. * Allergy to any product used in the protocol. * Serious medical or psychiatric illness or concomitant medication, which, in the judgment of the principal investigator, might interfere with the subject's ability to respond to or tolerate the treatment or complete the trial.