A Study Evaluating the Safety and Efficacy of Brexucabtagene Autoleucel (KTE-X19) in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ZUMA-3)

Key Inclusion Criteria

• Relapsed or refractory B-precursor ALL defined as one of the following:
• Primary refractory disease
• First relapse if first remission ≤ 12 months
• Relapsed or refractory disease after 2 or more lines of systemic therapy
• Relapsed or refractory disease after allogeneic transplant provided individuals is at least 100 days from stem cell transplant at the time of enrollment
• Morphological disease in the bone marrow (≥ 5% blasts)
• Individuals with Philadelphia chromosome positive (Ph+) disease are eligible if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different TKIs
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1
• Adequate renal, hepatic, pulmonary and cardiac function defined as:
• Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min
• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 x 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, and no clinically significant arrhythmias
• Baseline oxygen saturation > 92% on room air
• In individuals previously treated with blinatumomab, cluster of differentiation 19 (CD19) tumor expression in bone marrow or peripheral blood.

Key Exclusion Criteria

• Diagnosis of Burkitt's leukemia/lymphoma according to World Health Organization (WHO) classification or chronic myelogenous leukemia lymphoid blast crisis
• History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years
• Isolated extramedullary disease
• Central nervous system (CNS) abnormalities
• Presence of CNS-3 disease or CNS-2 disease with neurological changes
• History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
• History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome or any other known bone marrow failure syndrome
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
• Primary immunodeficiency
• Known infection with human immunodeficiency virus (HIV), hepatitis B (HBsAg positive) or hepatitis C virus.
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
• Prior medication:
• Salvage chemotherapy including TKIs for Ph+ ALL within 1 week prior to enrollment
• Prior CD19 directed therapy other than blinatumomab
• Treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis
• Donor lymphocyte infusion (DLI) within 28 days prior to enrollment
• Any drug used for graft-versus-host disease (GVHD) within 4 weeks prior to enrollment
• At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy prior to enrollment
• Corticosteroid therapy for 7 days prior to enrollment
• Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted
• Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by International Bone Marrow Transplant Registry (IBMTR) index; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment
• Live vaccine ≤ 4 weeks prior to enrol