CLINICAL TRIAL / NCT02608385

Inclusion Criteria: - Willing and able to provide written informed consent/assent for the trial. - Aged 18 years or older - Have a histologically confirmed advanced solid tumor for which curative treatment is not available. - Have undergone all appropriate standard of care treatment options (in the opinion of the treating investigator). Patients with NSCLC must have undergone EGFR and ALK testing and have received appropriate initial therapy. - Have measurable disease based on RECIST 1.1 including at least two tumor lesions that meet criteria for multi-organ site ablative radiation therapy (MOSART) SBRT radiation. - 0.25 cc to 65 cc of viable tumor (i.e. primary disease or metastases) approximately 5cm in maximal dimension. Tumors larger than 65 cc can be partially treated. Patients accruing to the expansion cohort for partially irradiated large tumors must have at least one site of disease >65cc. - Metastases located in lung, liver, mediastinal/cervical node, Spinal/Paraspinal, Osseous, abdominal-pelvic (lymph node/adrenal gland) - For biopsy patients: Be willing to undergo repeat biopsy of a tumor lesion before treatment and after radiation. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may be exempted from this requirement after consultation with the Principal Investigator. - Have a performance status of 0 or 1 on the ECOG Performance Scale. - Demonstrate adequate organ function - Absolute neutrophil count (ANC) ≥ 1,500 /mcL - Platelets ≥ 100,000 / mcL - Hemoglobin ≥ 8 g/dL - Serum creatinine OR Measured or calculateda creatinine clearance ≤ 1.5 X upper limit of normal (ULN) OR ≥ 50 mL/min for subject with creatinine levels > 1.5 X institutional ULN - Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN - AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases - Albumin ≥ 3.0 mg/dL - Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. - Female subjects 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. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. - Male subjects 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. - Have an investigator determined life expectancy of at least 6 months. Exclusion Criteria: - 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 the first dose of treatment. - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose of >10 mg Prednisone daily or equivalent at time of first dose of trial treatment. - Has a known history of active TB (Bacillus Tuberculosis) - Hypersensitivity to pembrolizumab or any of its excipients. - Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from side effects due to agents administered more than 4 weeks earlier. - Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 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: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. - Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. - Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects 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. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. - 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. - Has known history of non-infectious pneumonitis that required steroids or active pneumonitis. - Has evidence of interstitial lung disease. - Has an active infection requiring systemic therapy. - Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. - Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. - Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. - If known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA qualitative is detected) then patient is not eligible for cohorts including SBRT to liver lesions. - Has received a live vaccine within 30 days of planned start of study therapy. - Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed, however intranasal influenza vaccines are live attenuated vaccines and are not allowed. - Has had prior radiation therapy (defined as >10% of prior prescription dose) to the area planning to be treated with SBRT Additional Criteria for Expansion Cohorts: - Partially Irradiated Large Volume Tumors Cohort - In addition to the criteria above, patients must have at least one lesion >65cc (~5cm diameter sphere) that is amenable to partial tumor irradiation. - Oligometastatic disease - In addition to the criteria above, patients must have disease limited to 4 total lesions or less, all of which are amenable to SBRT. Patients with oligometastatic disease at presentation or oligorecurrent disease are eligible. Patients who had more than 4 sites of disease previously, but had a complete response at other sites and limited progressive disease to 4 sites are eligible for participation. Partial tumor irradiation for lesions >65cc is permitted in this expansion cohort.