Sequencing of Stereotactic Ablative Body Radiotherapy in Combination With PD-1 Blockade Using Pembrolizumab in Metastatic Non-Small Cell Lung Carcinoma

Inclusion Criteria: 1. Have provided written informed consent for the trial. 2. Be ≥ 18 years of age on day of signing informed consent. 3. Have at least one lesion not planned for SABR that is measurable disease based on RECIST 1.1. 4. Patients must have a histologically or cytologically confirmed metastatic non-small cell lung cancer. 5. Patients with disease previously untreated with systemic therapy must have ≥ 50% PD-L1 staining and patients who have previously received systemic therapy must have ≥ 1% PD-L1 staining on immunohistochemistry 6. Patients must have at least 1-3 lesions suitable for treatment with stereotactic radiotherapy. 7. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumour lesion where feasible. Newly-obtained is defined as a specimen obtained up to 12 weeks prior to randomisation. Patients for whom newly-obtained samples cannot be provided (e.g. inaccessible or patient safety concern) may submit an archived specimen only upon agreement from the study principal investigators. 8. Have a performance status of 0-1 on the ECOG Performance Scale (see Appendix 1). 9. Demonstrate adequate organ function as defined in table 3 below, all screening labs should be performed within 10 days of randomisation. Table 3 Adequate Organ Function Laboratory Values Absolute neutrophil count (ANC) ≥1.5x109/L Platelets≥100x109L Haemoglobin ≥90 g/L without transfusion or EPO dependency (within 7 days of assessment) Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥30 mL/min for patients with creatinine levels \> 1.5 X institutional ULN Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT)≤ 2.5 X ULN OR ≤ 5 X ULN for patients with liver metastases International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 10. Life expectancy \> 3 months. 11. Be willing and able to comply with all study requirements, including treatment, attending assessments and follow-up. 12. Female patient of childbearing potential should have a negative urine or serum pregnancy within 7 days of randomisation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 13. Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (See Section 8.10). Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. 14. Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Exclusion Criteria: 1. Has had previous high dose radiotherapy (biological equivalent of \>30Gy in 10#) to an area to be treated which includes vertebral bodies (see below). Note: Previous high dose radiotherapy is defined as a biological equivalent dose to above that of 30 Gy in 10 fractions using an alpha/beta ratio (50) of 3. Where a patient has received radiotherapy to an equivalent or lower dose than defined above, stereotactic radiotherapy of the area may be considered. In doing so, assessment of the volume and total dose received by any overlap region must be made, and documented by generating a cumulative plan incorporating both the previous and current treatment fields. It is the treating radiation oncologist's responsibility to review both the current plan and the cumulative plan inclusive of previous radiotherapy. 2. Has had previous thoracic radiotherapy of \> 36Gy within the 6 months prior to randomisation. 3. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with small asymptomatic or previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of enlarging brain metastases, and are not using steroids for intracranial neurological symptoms at least 7 days prior to trial randomisation. This exception does not include leptomeningeal disease which is excluded regardless of clinical stability. 4. Has evidence of Spinal Cord Compression. 5. Has a Spinal Instability Neoplastic Score ≥ 7 unless lesion reviewed by a neurosurgical service and considered stable (see Appendix 2). 6. Requires surgical fixation of bone lesion for stability. All surgical fixation and instrumentation must be completed before randomisation on study. 7. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of randomisation. 8. Has a diagnosis of immunodeficiency. 9. Has a known history of active TB (Bacillus Tuberculosis). 10. Has a hypersensitivity to pembrolizumab or any of its excipients. 11. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to randomisation or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 12. Has diagnosed and/or treated additional malignancy within 5 years prior to randomisation with the exception of: curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, curatively treated early stage cervical cancer, breast cancer or prostate cancer with no evidence of active disease. Other exceptions may be considered following consultation with the principal investigator 13. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 14. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 15. Has had any systemic anti-cancer therapy or radiation therapy within 4 weeks prior to randomisation 16. Has known interstitial lung disease 17. Has an active infection requiring systemic therapy. 18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator. 19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 20. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 21. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 22. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). 23. Has received a live vaccine within 30 days of randomisation. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu- Mist®) are live attenuated vaccines, and are not allowed. -