Palliative RT & Anti-PD-1/PD-L1 Checkpoint Blockade in Metastatic Merkel Cell Carcinoma

Inclusion Criteria: * Histologically confirmed metastatic Merkel Cell Carcinoma. * Patients are eligible if they have received no more than 3 prior systemic treatments, inclusive of systemic adjuvant therapy. This includes previously untreated patients. * Subjects with brain metastases and/or carcinomatous meningitis are eligible providing they are neurologically stable (if systemic steroids are required, subjects should be stable on the lowest clinically effective dose, as steroids may interfere with the activity of immunotherapy if administered at the time of the first Anti-PD-1/PD-L1 dose.) * Availability of tumor tissue (fresh or archival) for central pathology review. * Must be at least 14 days since treatment with chemotherapy, biochemotherapy, surgery, or immunotherapy, and recovered (baseline or residual Grade 1 toxicity) from any clinically significant toxicity experienced during treatment before the first dose of pembrolizumab therapy. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Life expectancy of ≥ 16 weeks. * Subjects must have measurable disease according to RECIST v1.1, and have baseline (screening/baseline) radiographic images, (e.g. CT, Positron emission tomography (PET)/CT or MRI brain, chest, abdomen, pelvis, to be determined by the attending physician) within 4 weeks of confirmation of eligibility and within 6 weeks before the initiation of pembrolizumab therapy. * Required values for initial laboratory tests: * White blood cells (WBC): ≥ 2000/µL (\~ 2 x 109/L) * Absolute Neutrophil Count (ANC): ≥ 1000/µL (\~ 1 x 109/L) Platelets: ≥ 50 x 103/µL (\~ 50 x 109/L) * Hemoglobin: ≥ 8 g/dL * Calculated creatinine clearance greater than 30 mL/min * Aspartate transaminase(AST)/alanine transaminase (ALT): Less than 2.5 x upper limit of normal (ULN) for subjects without liver metastasis, less than 5 times ULN for liver metastases * Bilirubin: less than 3.0 x ULN (except for subjects with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL) * Non-clinically significant laboratory abnormalities such as lipase elevation would not be an exclusion. * No known active or chronic infection with HIV, Hepatitis B, or Hepatitis C, or active infection requiring systemic antibiotics. Testing for the above is not required unless clinically suspected. * At least one measurable site of disease (≥ 10 mm as per RECIST v1.1 except for lymph nodes that must be 15 mm or greater on the short axis) outside of the planned palliative radiation therapy field. * Require radiation therapy for palliation of symptoms or to prevent local progression of disease and associated complications and/or symptoms from metastases. * Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study \[and for up to 26 weeks after the last dose of investigational product\] in such a manner that the risk of pregnancy is minimized. * WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post-menopausal is defined as: * Amenorrhea ≥ 12 consecutive months without another cause, or * For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level \> 35 mIU/mL * Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 1 week prior to the start of investigational product. * Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study \[and for up to 26 weeks after the last dose of investigational product\] in such a manner that the risk of pregnancy is minimized. Exclusion Criteria: * WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 26 weeks after the last dose of investigational product. * Women who are pregnant or breastfeeding. * Women with a positive pregnancy test on enrollment or before investigational product administration. * Subjects on any other systemic therapy for cancer, including any other experimental treatment within 2 weeks of scheduled first dose of pembrolizumab. * Prior treatment with an anti-PD-1/PD-L1 antibody if treatment failure was due to AEs. If a subject was discontinued from the prior anti-PD-1/PD-L1 treatment due to an Adverse events (AE) or Serious adverse events (SAE), regardless of the type of event, that discontinuation constitutes an exclusion criterion. If AEs were serious enough to require a subject's withdrawal from prior treatment, the subject should be excluded from this study. The exception to the above are non-clinically significant immune-related laboratory abnormalities - these are not automatic exclusions - e.g. asymptomatic elevated amylase; responsiveness to steroids. In situations above - e.g. non-clinically significant immune-related laboratory abnormalities, each case will be considered individually and a decision made by the study team. * A history of AEs with prior IL-2 or Interferon will not preclude subjects from entering the current study. * Autoimmune disease: Poorly controlled autoimmune disease is excluded. Well controlled autoimmune disease (e.g. well controlled RA) will be assessed by the study team and a decision made regarding eligibility based on the degree of immunosuppression and severity of symptoms. * Any subject who has a life-threatening condition that requires high-dose immunosuppressant(s). Steroid doses greater than 20 mg/day will exclude the patient from participation in the trial. * Presence of known hepatitis B or hepatitis C infection, regardless of control on antiviral therapy. * Subjects who have another active, concurrent, malignant disease are not eligible, with the exception of subjects with adequately treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or other cancers that are in remission/not measurable. Patients will be excluded if they have any known additional malignancy that requires active treatment while on treatment for Merkel Cell Carcinoma. * Bilirubin/total bilirubin 3 or more X ULN unless conjugated bilirubin is less than or equal to the ULN. * Evidence of symptomatic interstitial lung disease or symptomatic active, noninfectious pneumonitis. * Participants with impaired cardiac function or clinically significant cardiac disease such as unstable angina/uncompensated heart failure, uncontrolled symptomatic arrhythmia. * Active autoimmune disease requiring systemic T-cell immunosuppression. * Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment. This exclusion does not include prophylactic antibiotics or topical antibiotics. * Known hypersensitivity to another monoclonal antibody, which cannot be controlled with standard measures (e.g. antihistamines and corticosteroids). * Any condition that would, in the investigator's judgment, interfere with full participation in the study. * Prior immune related AEs not meeting the conditions above. * Prisoners or subjects who are involuntarily incarcerated. * Subjects with acute or poorly controlled psychiatric illness or subjects who are compulsorily detained for physical (e.g., infectious disease) illness, with the exception of patients that are well supported and able to participate (e.g. paraplegia from a motor vehicle accident). * Any underlying medical or psychiatric condition that, in the opinion of the investigator, could make the administration of anti-PD-1/PD-L1 hazardous or could obscure the interpretation of adverse events. * Any live vaccine therapy for up to 4 weeks before or after any dose of immunotherapy on this trial. * Any investigational agents within 2 weeks of scheduled first dose of pembrolizumab.