This is a Phase 1b/2, multicenter, open-label, study of prizloncabtagene autoleucel (prizlo-cel), an autologous dual targeting chimeric antigen receptor (CAR) T-cell therapy targeting both cluster of differentiation (CD) CD20 and CD19, for the treatment of adult participants with relapsed or refractory (r/r) B-Cell non-Hodgkin lymphoma (B-NHL) or frontline high-risk diffuse large B-cell lymphoma (DLBCL).

Inclusion Criteria:

• Participant must be greater than or equal to (>=) 18 years of age, at the time of signing informed consent
• Tumor must be histologically confirmed cluster of differentiation (CD)19 and/or CD20 positive
• Must meet the indications for each subtype in Phase 1b as specified in protocol and Phase 2 participants must have following: Diagnosis of Large B-cell lymphoma (LBCL), Follicular large B-cell lymphoma (FLBCL), or transformation of indolent lymphoma; Received at least 2 prior lines of systemic therapy; Relapsed or refractory disease defined as 1 or more of the following: Stable disease or Progressive disease (PD) as best response to most recent anti-lymphoma therapy OR disease progression or recurrence after a partial response (PR) or complete response (CR) to most recent anti lymphoma therapy; cohort specific requirements as mentioned in protocol
• Measurable disease as defined by Lugano 2014 classification
• Eastern cooperative oncology group (ECOG) performance status of 0 to 2

Exclusion Criteria:

• History of symptomatic deep vein thrombosis or pulmonary embolism within six months of apheresis (line associated deep vein thrombosis is allowed)
• History of stroke, unstable angina, myocardial infarction, congestive heart failure New York Heart Association (NYHA) Class III or IV, severe cardiomyopathy or ventricular arrhythmia requiring medication or mechanical control within 6 months of apheresis
• History of a seizure disorder, dementia, cerebellar disease or neurodegenerative disorder
• Known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
• Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones)
• Evidence of active viral or bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic fungal infection
• Diagnosis of Human herpes virus (HHV) 8-positive DLBCL or T cell/histiocyte-rich large B-cell lymphoma or Burkitt and high-grade B-cell lymphoma with 11q aberrations (previously Burkitt-like lymphoma) or Richter's transformation or Lymphomatoid granulomatosis or Plasmablastic lymphoma or Waldenstrom's Macroglobulinemia
• Any prior solid organ or allogeneic stem cell transplantation
• Autologous stem cell transplant within 12 weeks of apheresis; Prior CAR-T cell therapy within 12 weeks of apheresis

The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu.