SCION: SABR and Checkpoint Inhibition of NSCLC

Inclusion Criteria: 1. Subjects must be competent, \>18yo at time of study entry, and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 2. Patients with histological diagnosis of NSCLC, all histological sub-types are eligible 3. Body weight \>30kg 4. ECOG Performance status (PS) 0-2. 5. Tumor stage T1-2 (≤5cm) N0 M0 (8th Edition of the TNM Classification for Lung Cancer) based on CT chest/abdomen, FDG-PET within 12 weeks of enrolment, and, where performed, EBUS-guided biopsy of hilar or mediastinal nodes within 8 weeks of enrolment. 6. Subject deemed medically inoperable, or subject deemed operable but declines surgery following surgical assessment. 7. Peripheral (outside a 2cm radius proximal bronchial tree) and central (within 2cm, but neither abuts nor invades proximal bronchial tree) tumors permitted. 8. Screening laboratory values for organ function must meet the following criteria within 14 days prior to cycle 1 day 1: * Bone Marrow: Absolute neutrophils ≥ 1.5 x 10\^9/L; Platelets ≥ 100 x 10\^9/L; Hemoglobin ≥ 90 g/L * Kidney: Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) ÷ 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 ÷ 72 x serum creatinine (mg/dL) * Liver: AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal * serum bilirubin ≤ 1.5 X ULN * Cardiac: LVEF ≥ 50% 9. No prior chemotherapy or planned adjuvant chemotherapy is allowed 10. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). 11. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 12. Must have a life expectancy of at least 12 weeks. Exclusion Criteria: 1. Any patient with malignancy which cannot be reliably defined on the treatment planning CT scan due to adjacent opacification from effusion, consolidation, or atelectasis. 2. History of allogenic organ transplantation. 3. History of active primary immunodeficiency 4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion: 1. Patients with vitiligo or alopecia 2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement 3. Any chronic skin condition that does not require systemic therapy 4. Patients without active disease in the last 5 years may be included but only after consultation with the study physician 5. Patients with celiac disease controlled by diet alone 5. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP. 6. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C and HIV. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 7. History of another primary malignancy except for: 1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease 3. Adequately treated carcinoma in situ without evidence of disease 8. Participation in another clinical study with an investigational product during the last 2 months 9. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study 10. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria 1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. 2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. 11. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 12. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug 13. Previous radiotherapy to the chest or mediastinum. Subjects who have had previous breast radiotherapy may be eligible at the discretion of the Sponsor. 14. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. 15. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 16. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart). 17. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: 1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) 2. Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent 3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 18. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy. 19. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 20. Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment. 21. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4: 1. Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy. 2. All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study. 3. Must not have experienced a ≥Grade 3 immune related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic. 4. Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day.