LINNOVATE: Lurbinectedin, Ipilimumab and Nivolumab for Soft Tissue Sarcoma (LINNOVATE)

Inclusion Criteria: Individuals must meet all of the inclusion criteria in order to be eligible to participate in the study, as follows: Male or Female ≥ 18 years of age Pathologically confirmed diagnosis of locally advanced unresectable or metastatic soft tissue sarcoma For the Phase 1 Part of Study, only previously treated participants will be enrolled. For the Phase 2 Part of Study, previously untreated participants will be enrolled. Ability to understand the purposes and risks of the study and has signed and dated a written informed consent form approved by the principal investigator's IRB/Ethics Committee Willingness to comply with all study procedures and availability for the duration of the study. Measurable disease by RECIST v1.1 ECOG performance status ≤ 1 Life expectancy of at least 3 months Acceptable liver function: Bilirubin < 1.5 times upper limit of normal (ULN; except subjects with Gilbert Syndrome who must have a total bilirubin level < 3.0 ULN); AST (SGOT), ALT (SGPT) and alkaline phosphatase < 3 x ULN (< 5 x ULN if liver metastases) Acceptable renal function: Creatinine < 1.5 times ULN or > 60 mL/min (using the Cockcroft Gault formula) Acceptable hematologic status (without hematologic support e.g. growth factors or transfusion within 21 days of first dose of study agents): ANC >= 1500 cells/μL; Platelet count >= 100,000/μL; Hemoglobin >= 9.0 g/dL; Normal PT, PTT, INR All women of childbearing potential must have a negative pregnancy test and all subjects must agree to use highly effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 5 months for women and 7 months for men after the last dose. Exclusion Criteria: All individuals meeting any of the exclusion criteria at baseline will be excluded from study participation, as follows: Subjects with untreated CNS metastases. Subjects are eligible if CNS metastases have been adequately treated and have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to treatment initiation. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of <10 mg daily prednisone (or equivalent) for at least 2 weeks prior to treatment initiation. Subjects with carcinomatous meningitis Anticancer treatment with radiation therapy, targeted therapy or other antitumor treatment within 2 weeks prior to study entry. Anticancer treatment with chemotherapy within 21 days prior to study entry. Subjects who participated in an investigational drug or device study within 14 days prior to study entry Females who are pregnant or breast-feeding Unwillingness or inability to comply with the study protocol for any reason Concurrent or prior immunotherapy with anti-CTLA4 or anti-PD-1 inhibitors Non-oncology vaccine therapy used for prevention of infectious disease within 4 weeks of trial enrollment Autoimmune disease including rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis and motor neuropathy considered to be of autoimmune origin (e.g. Guillain-Barre Syndrome) Systemic immunosuppression, including HIV positive status with or without AIDS Skin rash (psoriasis, eczema) affecting > 25% body surface area Inflammatory bowel disease (Crohn's or ulcerative colitis) Ongoing or uncontrolled diarrhea within 4 weeks of trial enrollment Recent history of acute diverticulitis, intraabdominal abscess or gastrointestinal obstruction within 6 months of trial enrollment, which are known risk factors for bowel perforation Participants with congestive heart failure or recent cardiac event Evidence of severe or uncontrolled systemic disease or any other concurrent condition, including psychiatric, which in the principal investigator or sub-investigator's opinion makes it undesirable for the participant to participate in the trial or which would jeopardize compliance with the trial Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Current, active, or previous history of heavy alcohol abuse Pituitary endocrinopathy Adrenal insufficiency or excess