PRIMARY OBJECTIVES:~I. To estimate the tumor response (Response Evaluation Criteria in Solid Tumors [RECIST]) at 4 months in patients with relapsed/refractory sarcoma. (Cohorts 1 and 2) II. To determine the event-free survival (EFS) rate at 4 months after initiation of the treatment in patients with relapsed/refractory osteosarcoma receiving novel immunotherapeutic agents. (Cohort 3)~SECONDARY OBJECTIVES:~I. To determine the progression-free survival (PFS) rate at 12 weeks after initiation of the treatment in patients with relapsed/refractory sarcoma receiving novel immunotherapeutic agents.~II. To estimate the tumor response (Immune-related Response Criteria [irRC] and RECIST) in patients with relapsed/refractory sarcoma.~III. To evaluate the safety and tolerability of receiving novel immunotherapeutic agents in patients with relapsed/refractory sarcoma.~IV. To estimate the median PFS and overall survival (OS) in patients with relapsed/refractory sarcoma receiving novel immunotherapeutic agents.~EXPLORATORY OBJECTIVES:~I. To determine expression of biomarkers (including but not limited to CD73, PD-1 and PD-L1) in pre & post treatment (tx) samples.~II. Quantification and characterization of the immune infiltrate (and other histologic and immunohistologic changes) from tissue samples prior to treatment initiation and post treatment (biopsy at week 6).~III. Identification/quantification of immunologic changes (CD4+, CD8+, Teff, Treg cells and NK cells) in peripheral blood.~IV. Determining an immunoscore based on baseline tumor sample (identification of molecular response/resistance patterns/future therapy options).~OUTLINE:~Patients receive oleclumab intravenously (IV) over 1 hour every 2 weeks for 5 doses, then every 4 weeks thereafter. Patients also receive durvalumab IV over 1 hour every 4 weeks. Cycle repeat every 28 days in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 30 days, and then every 3 months for up to 5 years.
This phase II trial investigates how well oleclumab and durvalumab work in treating patients with sarcoma that has come back (recurrent) or does not respond to treatment (refractory) or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as oleclumab and durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.