Inclusion Criteria:

• Histologically proven large B-cell lymphoma, including the following types defined by (Swerdlow et al, 2016):
  • DLBCL not otherwise specified (activated B cell/germinal center B cell [ABC/GCB]);
  • HGBCL with or without MYC and BCL2 and/or BCL6 rearrangement;
  • DLBCL arising from FL;
  • T-cell/histiocyte rich large B-cell lymphoma;
  • DLBCL associated with chronic inflammation;
  • Primary cutaneous DLBCL, leg type;
  • Epstein-Barr virus (EBV) + DLBCL.
• Relapsed or chemotherapy-refractory disease, defined as one or more of the following:
  • No response to first-line therapy (primary refractory disease); subjects who are intolerant to first-line therapy chemotherapy are excluded:
    • Progressive disease (PD) as best response to first-line therapy;
    • SD as best response after at least 4 cycles of first-line therapy (e.g., 4 cycles of R-CHOP) with SD duration no longer than 6 months from last dose of therapy.
  • No response to second- or greater-lines of therapy:
    • PD as best response to most recent therapy regimen;
    • SD as best response after at least 2 cycles of last line of therapy with SD duration no longer than 6 months from last dose of therapy.
  • Refractory post-ASCT:
    • Disease progression or relapsed ≤ 12 months after ASCT (must have biopsy proven recurrence in relapsed subjects).
    • If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy.
  • Relapsed or refractory LBCL including DLBCL, TFL, and HGBCL after 2 or more lines of systemic therapy that is defined by and aligns with currently approved indications
    • Relapsed disease after 2 or more lines of systemic therapy OR
    • Best response that is less than a CR to a second or greater line of systemic therapy
• At least 1 measureable lesion according to the Lugano Classification (Cheson et al, 2014). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
• Subjects must have received adequate prior therapy, including at a minimum:
  • Anti-CD20 mAb unless investigator determines that tumor is CD20-negative; and
  • An anthracycline containing chemotherapy regimen/
• No radiographic evidence, suspicion, and/or history of central nervous system (CNS) involvement of lymphoma/
• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis.
• Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities, such as alopecia).
• Age 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Absolute neutrophil count (ANC) ≥ 1,000/μL.
• Platelet count ≥75,000/μL.
• Absolute lymphocyte count ≥100/μL.
• Adequate renal, hepatic, pulmonary, and cardiac function defined as:
  • Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min;
  • Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 upper limit of normal (ULN);
  • Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert’s syndrome;
  • Cardiac ejection fraction ≥ 50% and no evidence of pericardial effusion within 180 days provided the subject did not receive an anthracycline-based treatment or experience a cardiac event or change in performance status;
  • No clinically significant pleural effusion;
  • Baseline oxygen saturation > 92% on room air.
• Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been post-menopausal for at least 2 years are not considered to be of childbearing potential).

Exclusion Criteria: 

• Histologically proven primary mediastinal B-cell lymphoma (PMBCL).
• History of Richter’s transformation of chronic lymphocytic leukemia (CLL).
• Prior CAR therapy or other genetically modified T-cell therapy.
• History of severe, immediate hypersensitivity reaction attributed to aminoglycosides.
• Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the sponsor’s medical monitor.
• History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection. Subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per  current Infectious Diseases Society of America (IDSA) guidelines or applicable country guidelines.
• Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted.
• Subjects with detectable cerebrospinal fluid (CSF) malignant cells, brain metastases, or a history of CNS lymphoma.
• History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• Subjects with cardiac atrial or cardiac ventricular lymphoma involvement.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
• Requirement for urgent therapy due to tumor mass effects (e.g., blood vessel compression, bowel obstruction, or transmural gastric involvement).
• Primary immunodeficiency
• History of autoimmune disease (e.g., Crohn’s, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years. Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and subjects with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study.
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
• Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Live vaccine ≤ 6 weeks prior to planned start of conditioning chemotherapy.
• Women of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
• Females who have undergone surgical sterilization or who have been post-menopausal for at least 2 years are not considered to be of childbearing potential.
• Subjects of both genders who are not willing to practice birth control from the time of consent through 90 days after the last dose of utomilumab and at least 6 months after the completion of conditioning chemotherapy.
• History of malignancy other than non-melanoma skin cancer in situ (e.g., cervix, bladder, breast) or low-grade (Gleason ≤ 6) prostate cancer or surveillance without any plans for treatment, unless disease-free for a least 3 years.
• ASCT within 6 weeks of planned enrollment Prior organ transplantation including prior allogeneic stem cell transplant (SCT).
• Prior CD19 targeted therapy with the exception of subjects who received axicabtagene ciloleucel in this study and are eligible for retreatment.
• Use of any standard or experimental anti-cancer therapy within 2 weeks prior to enrollment, including cytoreductive therapy and radiotherapy, immunotherapy, or cytokine therapy (except for erythropoietin).
• Prior treatment with PD-L1 inhibitor, PD-1 inhibitor, anti-CTLA4, anti-CD137 (4-1BB), anti-OX40 or other immune checkpoint blockade or activator therapy.
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IF] and interleukin-2 [IL-2]) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first utomilumab dose.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest computed tomography (CT) scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed.
• In the investigator’s judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.