Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma

The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in participants with high-risk large B-cell lymphoma.

After the end of KTE-C19-112 (ZUMA-12), participants who received an infusion of axicabtagene ciloleucel will complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968.


Eligibility Criteria:
Key Inclusion Criteria:

* Histologically confirmed large B-cell lymphoma
* High-grade large B-cell lymphoma
* Individuals must have a positive interim positron emission tomography (PET) (Deauville PET score of 4 or 5) after 2 cycles (PET2+) of chemoimmunotherapy
* No 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 ≥ 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 (ALT) and aspartate aminotransferase (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%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
* No clinically significant pleural effusion
* Baseline oxygen saturation \> 92% on room air

Key Exclusion Criteria:

* History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years
* History of Richter's transformation of chronic lymphocytic leukemia or primary mediastinal B-cell lymphoma
* History of autologous or allogeneic stem cell transplant
* Prior CD19-targeted therapy
* Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
* Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management
* History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection
* Presence of any indwelling line or drain dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted
* Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or active 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
* History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
* History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
* History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment

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