Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Utomilumab in Adults With Refractory Large B-cell Lymphoma

Key Inclusion Criteria:

   - Histologically proven large B-cell lymphoma including the following types:

      - Diffuse large B cell lymphoma (DLBCL) not otherwise specified (ABC/GCB)

      - High grade B-cell lymphoma (HGBCL) with or without MYC and BCL2 and/or BCL6
      rearrangement

      - DLBCL arising from follicular lymphoma

      - 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 systemic chemotherapy are excluded

         - Progressive disease (PD) as best response to first-line therapy

         - Stable disease (SD) as best response after at least 4 cycles of first-line
         therapy (eg, 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 OR

      - Refractory post-autologous stem cell transplant (ASCT)

         - Disease progression or relapsed . 12 months after ASCT (must have biopsy
         proven recurrence in relapsed participant)

         - if salvage therapy is given post-ASCT, the participant 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
      indication:

         - Relapsed disease after 2 or more lines of systemic therapy

         - Best response that is less than a CR to 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.

   - Participant must have received adequate prior therapy including at a minimum:

      - Anti-CD20 monoclonal antibody 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

   - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

   - Absolute neutrophil count (ANC) ≥ 1000/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 individuals 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

Key Exclusion Criteria:

   - Histologically proven primary mediastinal B-cell lymphoma (PMBCL)

   - History of Richter's transformation of chronic lymphocytic lymphoma (CLL)

   - Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy

   - History of severe, immediate hypersensitivity reaction attributed to aminoglycosides

   - History of HIV infection or acute or chronic active hepatitis B or C infection.
   Individuals 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

   - Individuals with detectable cerebrospinal fluid 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

   - Individuals 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 (eg, blood vessel
   compression, bowel obstruction, or transmural gastric involvement

   - Primary immunodeficiency

   - History of autoimmune disease (eg, Crohn's, rheumatoid arthritis, systemic lupus)
   resulting in end organ injury or requiring systemic immunosuppression/systemic disease
   modifying agents within the last 2 years. Patients with a history of
   autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and
   patients 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

   - Autologous stem cell transplant within 6 weeks of planned enrollment

   - Prior organ transplantation including prior allogeneic stem cell transplant (SCT)

   - 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

   - History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis
   obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
   pneumonitis per chest 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.