Safety, Tolerability, and Efficacy of Doxorubicin and Pembrolizumab for Sarcoma

Inclusion Criteria 1. Be willing and able to provide written informed consent for the trial. 2. Must have a histologically confirmed diagnosis of unresectable or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy. Patients with Ewings sarcoma, osteosarcoma, chondrosarcoma, Kaposis sarcoma, gastrointestinal stromal tumors (GIST), clear cell sarcoma, alveolar soft part sarcoma and any other soft tissue or bone sarcoma felt to be chemotherapy resistant in the opinion of the Sponsor-Investigator will be excluded. 3. Must not have received prior treatment with an anthracycline chemotherapy (eg, doxorubicin) and/or anti-PD-1/PD-L1 therapy. 4. May have had any number of prior systemic cytotoxic therapies for unresectable/metastatic disease. 5. Must have at least one radiologically measurable lesion as per RECIST 1.1 defined as a lesion that is 10mm in longest diameter or lymph node that is 15mm in short axis imaged by CT scan or MRI. Tumors with previously irradiated field will be designated as nontarget lesions unless progression is documented or a biopsy is obtained to confirm persistence of at least 90 days following completion of radiotherapy. 6. All subjects with accessible tumor will be asked to provide a fresh tumor biopsy if they can be safely biopsied in the opinion of the investigator. Recently obtained archived core or excisional biopsy of a tumor lesion (obtained up to 12 months prior to Cycle 1 Day 1) may be substituted only if the subject is unwilling or unable (e.g. inaccessible or subject safety concern) to undergo a fresh tumor biopsy. Subjects who are unwilling or unable to have a fresh tumor biopsy and do not have recently obtained archived tissue available may submit an archived specimen (obtained \> 12 months prior to Cycle 1 Day 1) only upon approval from the Sponsor-Investigator. 7. Be at least 12 years of age on day of signing informed consent. Assent will be obtained in appropriately aged subjects per institutional guidelines. 8. ECOG performance status 0 or 1. 9. Life expectancy of at least 3 months per the Investigator. 10. Have adequate organ function as indicated by the laboratory values in Table 1 of protocol. All screening labs should be performed within 10 days of treatment initiation. PT/INR and PTT must be performed within 7 days of study treatment initiation for subjects on anti-coagulants such as coumadin/heparin. 11. The subject has left ventricular ejection fraction (LVEF) greater than or equal to 50% assessed within 21 days prior to study regimen initiation. 12. Subjects must not be expecting to conceive or father children within the timeframe referenced below. Subjects of childbearing potential must be willing to adhere to the contraception requirement as described in Section 3.3.2 from the day of the screening visit (or 14 days prior to the initiation of study treatment for oral contraception) throughout the study period up to 120 days after the last dose of pembrolizumab and/or up to 180 days after the last dose of doxorubicin. If there is any question that a subject of childbearing potential will not reliably comply with the requirements for contraception, that subject should not be entered into the study. 13. Female subjects of childbearing potential must have a negative urine or serum pregnancy test at screening (within 72 hours of first dose of study treatment). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the subject to be eligible. 14. Subject has voluntarily agreed to participate by giving written informed consent for the trial. The subject may also provide consent for Optional and Future Studies-Biospecimen Collection. However, the subject may participate in the main trial without participating in Optional and Future Studies. Exclusion Criteria 1. Currently participating and receiving study therapy or have participated in a study of an investigational agent and received study therapy or used an investigational device within 30 days of the first dose of study regimen. 2. Have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study regimen. 3. Have a known history of active TB (Bacillus Tuberculosis). 4. Have had a prior anti-cancer monoclonal antibody (mAb) given to treat malignancy within 4 weeks prior to the first dose of study regimen or have not recovered (i.e. less than or equal to Grade 1 or at baseline) from adverse events due to previous mAbs. 5. Have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study regimen or who have not recovered (i.e. less than or equal to Grade 1 or at baseline) from adverse events due to previous chemotherapy, targeted small molecule therapy, or radiation therapy. Note: Subjects with less than or equal to Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subjects have received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy as determined by the Investigator. 6. Have 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. 7. Have 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 study regimen 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 the first dose of the study regimen. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 8. Have 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. 9. Have known history of, or any evidence of active, non-infectious pneumonitis. 10. Have an active infection requiring systemic therapy (uncomplicated urinary tract infection treated with oral antibiotics is permitted). 11. Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subjects participation for the full duration of the trial, or is not in the best interest of the subjects to participate, in the opinion of the treating Investigator. 12. Have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as determined by the Investigator. 13. Are pregnant or breastfeeding 14. Have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 15. Have a known history of Human Immunodeficiency Virus infection (e.g. HIV 1/2 antibodies). 16. Have known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA \[qualitative\] is detected). 17. Have 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 (e.g. Flu-Mist) are live attenuated vaccines, and are not allowed.