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

- 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

- 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

- 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.