Pembrolizumab and Palliative Radiotherapy in Lung

Inclusion Criteria:

1. Be willing and able to provide written informed consent for the trial.
2. Have measurable disease based on RECIST 1.1.
3. Histologically verified NSCLC including squamous cell carcinoma, adenocarcinoma, adenosquamous or large cell anaplastic carcinoma; requiring palliative radiotherapy for which no curative therapy exists will be recruited into the trial.
4. Patients are permitted to have extrathoracic disease which will not be encompassed in the radiotherapy field. This disease will be assessed for abscopal response
5. Ability to tolerate a course of palliative radiotherapy to the lung.
6. Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumour lesion.
7. Have a performance status of 0-2 on the ECOG Performance Scale.
8. Demonstrate adequate organ function, all screening labs should be performed within 10 days of confirmation of eligibility.
9. Patient's lung function tests at baseline should have an FEV1 \> 0.8L or \> 30%.
10. See protocol section.

Exclusion Criteria:

1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
3. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
4. Previous radiotherapy to the lung
5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

   Note: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.

   Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
6. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with 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 new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
8. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require the use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
9. Has evidence of interstitial lung disease or active, noninfectious pneumonitis.
10. Has received prior therapy with an antiPD1, antiPDL1, antiPDL2, antiCD137, or anti Cytotoxic T-lymphocyte associated antigen4 (CTLA4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
11. See protocol section.