Immunotherapy-Chemo combo takes on advanced sarcoma

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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