Inclusion Criteria:
* Diagnosis of metastatic or locally advanced and unresectable high-grade soft tissue sarcoma. Unresectable is defined as:
1. primary tumor cannot be safely removed surgically, or
2. primary tumor would benefit from systemic therapy prior to a surgical approach
* Be willing and able to provide written informed consent
* Must consent to mandatory tumor biopsy (if deemed safe and feasible) for research studies at screening, if archival tissue is not available, and at C1D15, C3D15.
* Age ≥ 18 years
* ECOG performance status ≤ 1
* Presence of measurable disease per RECIST v1.1
* Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment.
* No prior systemic therapy (see exclusion criteria, below)
* Negative serum pregnancy test in women of childbearing potential
* Patients with chronic HBV (HBsAg-positive with undetectable or low HBV DNA and normal ALT, or HBsAg-negative with anti-HBc-positive serology) and HCV (completed curative antiviral treatment with HCV viral load below the limit of quantification) may be eligible
* Patients with HBV should be treated with suppressive antiviral therapy prior to enrollment
* Patients with HCV must have completed curative therapy and have negative HCV viral load
* Adequate organ function, as defined in Table 2:
Table 2: Laboratory Parameters Required for Study Inclusion
Hematological Absolute neutrophil count (ANC): ≥ 1,500 /mcL Platelets: ≥ 75,000 / mcL Hemoglobin: ≥ 9g/dL or ≥ 5.6 mmol/L
Renal Serum creatinine: ≤ 1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance: ≥ 60 mL/min for patient with creatinine levels \> 1.5 X institutional ULN (GFR can also be used in place of creatinine orCrCl)
Hepatic Serum total bilirubin: ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 ULN except patients with Gilbert's disease (≤ 3x ULN) AST (SGOT) and ALT (SGPT): ≤ 2.5 X ULN OR ≤ 5 X ULN for patients with liver metastases
Exclusion Criteria:
* Received any systemic therapy in the advanced or metastatic setting
* Adjuvant or neoadjuvant therapies received ≥ 1 year prior to enrollment are permitted
* Unstable or deteriorating cardiovascular disease within the previous 6 months, including:
* Unstable angina or myocardial infarction
* CVA/stroke
* New York Heart Association \[NYHA\] Class III or IV congestive heart failure
* Uncontrolled clinically significant arrhythmias
* Current use of immunosuppressive medication, EXCEPT for the following:
* Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
* Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent
* Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
* Evidence of clinically significant immunosuppression such as the following:
* Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
* Concurrent opportunistic infection
* Receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \> 10 mg/day of prednisone or equivalent within 2 months prior to enrollment
* History or evidence of symptomatic autoimmune disease in past 2 years prior to enrollment.
* Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease
* Uncontrolled HIV infection, as defined by one or more of the following:
* Patients with CD4+ T-cell (CD4+) counts \< 350 cells/uL
* Patients with a history of an opportunistic infection secondary to AIDS
* Patients on anti-microbials with drug-drug interactions with the study drugs on this protocol, who cannot be switched to alternative anti-microbials
* Patients on antiretroviral therapy \< 4 weeks
* Patients with HIV viral load \> 400 copies/mL
* Active Hepatitis B or Hepatitis C
* Patients who have received a live vaccine within 30 days of the start date of the planned study therapy (with the exception of COVID-19 vaccines)
* History of active TB (Bacillus Tuberculosis)
* Radiation therapy within 2 weeks prior to study day 1
* If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
* Women who are pregnant or breast feeding
* Patients expecting to conceive or father children within the projected duration of the trial, starting with the visit through 180 days after the last dose of study treatment(s)
* Prior organ transplantation including allogenic stem-cell transplantation
* Active infection requiring systemic therapy
* Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3)
* Patients with prior history of interstitial lung disease and clinically significant pulmonary compromise, including those who have a requirement for supplemental oxygen use to maintain adequate oxygenation
