Multi-Arm Study to Test the Efficacy of Immunotherapeutic Agents in Multiple Sarcoma Subtypes

Inclusion Criteria

• Age: >/= 18 years of age
• Histologically or cytologically confirmed sarcoma that fall into one of the following categories Patients with low-grade tumors are eligible if there is definite evidence of metastasis or progression (defined as at least a 10% increase in the cumulative sum of the longest diameters within a 3 month period): 1. Adipocytic tumors (Well-differentiated/dedifferentiated liposarcoma, myxoid liposarcoma, pleomorphic liposarcoma) 2. Vascular tumors (leiomyosarcoma, angiosarcoma) 3. Undifferentiated pleomorphic sarcoma 4. Synovial sarcoma 5. Osteosarcoma 6. Other sarcoma histologies
• Must have received and have progressed, are refractory or intolerant to standard therapy appropriate for the specific sarcoma subtype, if there is a standard therapy for the subtype (i.e. Progressing well-differentiated liposarcoma, clear cell sarcoma etc do not require prior therapy).
• Subjects must have at least 1 lesion that is measurable by irRECIST a. A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable per irRECIST, and has clearly progressed. b. Subjects undergoing fresh tumor biopsies must have additional non-target lesions that can be biopsied at acceptable risk as judged by the investigator or if no other lesion suitable for biopsy, then an irRECIST target lesion used for biopsy must be >/= 2 cm in longest diameter.
• Subjects must consent to provide archived tumor specimens for correlative biomarker studies. Tumor tissue must be identified and availability confirmed prior to initiation of study therapy. In the setting where archival material is unavailable or unsuitable for use, or there have been multiple intervening therapies subjects must consent and undergo fresh tumor biopsy. A tumor lesion planned for biopsy must not be an irRECIST target lesion unless there are no other lesions suitable for biopsy and lesion used for biopsy is >/= 2 cm in longest diameter.
• ECOG performance status of 0 or 1
• Adequate organ function as determined by (lymphocyte count): a. Hematological (without growth factor or transfusion support): i. Absolute neutrophil count >/= 1.5 x 10^9/L (1,500/mm^3) ii. Platelet count >/= 90 × 10^9/L (100,000/mm^3) iii. Hemoglobin >/= 8.0 g/dL within first 2 weeks prior to first dose of investigational product b. Renal: i. Calculated creatinine clearance (CrCl) or 24-hour urine CrCl > 50 mL/min Cockcroft-Gault formula (using actual body weight) will be used to calculate CrCl, except for pts with Osteosarcoma who will be allowed to participate with an estimated creatinine clearance (CrCl) of > 40 mL/min, as calculated by the Cockcroft-Gault equation. c. Hepatic: i. Total bilirubin </= 1.5 × ULN; for subjects with documented/suspected Gilbert's disease, bilirubin </= 3 × ULN ii. AST and ALT </= 2.5 × ULN; for subjects hepatic metastases, ALT and AST </= 5 × ULN
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 180 days after the final dose of investigational product.
• Life expectancy of at least 6 months.
• Ability to understand the purposes and risks of the study and has signed a written consent form approved by the investigator's IRB/Ethics Committee

Exclusion Criteria

• Prior therapy with anti-PD1, anti-PD-L1 or anti-CTLA-4 antibody
• Active or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegener syndrome) within the past 2 years. Subjects with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression. Subjects previously treated central nervous system metastases that are radi