Inclusion Criteria:

• Age ≥ 18 years (Age ≥ 12 years for patients with bone sarcomas).
• Histologically confirmed diagnosis of unresectable, recurrent, and/or metastatic high grade soft-tissue or bone sarcoma of one of the following subtypes: soft tissue sarcomas (leiomyosarcoma, poorly differentiated/de-differentiated liposarcoma, high grade pleomorphic undifferentiated sarcoma/MFH, MPNST and synovial sarcoma), and bone sarcomas (Ewing sarcoma, osteosarcoma, and chondrosarcoma [de-differentiated or mesenchymal]).
• ECOG Performance Status of 0 or 1.
• At least one site of measurable disease on CT/MRI scans as defined by RECIST 1.1 . Baseline imaging must be performed within 30 days of Day 1 of study.
• At least one site of accessible disease for pre- and post-treatment core biopsies.
• Patients may have received 1-3 prior systemic therapies.
• Adequate organ function.
• Written, voluntary informed consent.
• Fertile men and women of childbearing potential must agree to use an effective method of birth control from Day 1 of study and for 3 months after last study drug administration. Women of childbearing potential include pre-menopausal women and women within the first 2 years of the onset of menopause. Women of childbearing potential must have a negative pregnancy test ≤ 72 hours prior to Day 1 of study.
• Effective methods of birth control include: surgically sterile, barrier device (condom, diaphragm), contraceptive coil, intrauterine device (IUD), and abstinence.
• Life expectancy of >12 weeks.
• Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical progression for at least 4 weeks prior to study entry, have no evidence of new or enlarging brain metastases, and are off steroids for at least 7 days before first dose of pembrolizumab.

Exclusion Criteria:

• Prior systemic therapy targeting PD-1: PD-L1 axis.
• Patients who are curable by conventional multidisciplinary management.
• Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.
• Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation < 2 weeks prior to Day 1 of study or who have not recovered adequately from side effects of such therapy.
• Patients who have active infections requiring therapy.
• Patients that are positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (HBsAg reactive), or Hepatitis C (HCV RNA (qualitative) is detected); patients with negative Hepatitis C antibody testing may not need RNA testing.
• Patients that have a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
• Patients who received systemic anti-cancer treatment prior to the first dose of study drug within the following time frames:
  • Patients who have received cyclical chemotherapy within a period of time that is shorter than the cycle length used for that treatment (e.g., 6 weeks for nitrosourea, mitomycin-C) prior to starting study drug;
  • Patients who have received biologic therapy (e.g., antibodies) within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug;
  • Patients who have been treated with a continuous or intermittent small molecule therapeutics within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug;
  • Patients who have received any other investigational agents within a period of time that is ≤ 5 t1/2 or less than the cycle length used for that treatment or ≤ 4 weeks (whichever is shorter) prior to starting study drug;
  • Patients who have received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug;
  • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug.
• Patients with active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Patients that require inhaled steroids or local steroid injections would not be excluded from the study. Patients with hypothyroidism not from autoimmune disease that is stable on hormone replacement will not be excluded from the study.
• Women who are pregnant or nursing/breastfeeding.
• Known hypersensitivity to pembrolizumab or another mAb.
• Patients with a history of non-infectious pneumonitis that has required a course of oral or intravenous steroids to assist with recovery, or interstitial lung disease.
• Patients with untreated central nervous system disease. Patients with controlled treated CNS lesions who have undergone surgery or stereotactic radiosurgery and stable for 4 weeks are eligible.
• Inability to comply with protocol required procedures.
• Patients with medical conditions that require chronic systemic corticosteroid therapy or require any other form of immunosuppressive medication; however, patients using physiologic replacement doses of hydrocortisone, or its equivalent, will be considered eligible for this study: up to 20 mg hydrocortisone (or 5 mg of prednisone) in the morning and 10 mg hydrocortisone (or 2.5 mg prednisone) in the evening.
• Patients with the risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess, abdominal carcinomatosis).
• Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment.
• Patients who have had allogeneic SCT/solid organ transplant.