A Study of the Efficacy and Safety of Lisocabtagene Maraleucel (Liso-cel) as First-Line Therapy in Adults With Transplant-Ineligible Primary Central Nervous System Lymphoma

Inclusion Criteria

* Participant must be 18 years or older at the time of signing the informed consent form (ICF).
* Histologically confirmed primary central nervous system (CNS) lymphoma (PCNSL) prior to screening, as assessed by local pathology.
* Transplant-ineligible based on physician's assessment and meeting at least one of the following criteria: age ≥65 years or HCT-CI (Hematopoietic Cell Transplantation-specific Comorbidity Index) score ≥3.
* Participant must be suitable, per investigator, to receive a high dose methotrexate (HD-MTX) based treatment regimen.
* Prior to signing ICF, anti-cancer therapy for the treatment of PCNSL must be limited to HD-MTX based standard of care regimens with a minimum of 4 and maximum of 6 doses of MTX. Corticosteroids used as part of standard-of-care management for PCNSL symptom control are permitted prior to ICF signature but must be discontinued at the time of ICF signature. For medical conditions other than PCNSL, non-therapeutic corticosteroids use may be permitted on study.
* Prior to enrollment, participant's disease must be sensitive to prior high-dose methotrexate-based (HD-MTX) regimens, as demonstrated by a complete response (CR, no remaining signs of PCNSL) or a partial response (PR, signs of PNCSL mostly gone) per Investigator's assessment, based on the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* No prior experimental treatments for PCNSL.
* Individuals of childbearing potential (IOCBP) must have a negative highly sensitive pregnancy test within 24 hours prior to the start of study intervention.

Exclusion Criteria

* Participant has a diagnosis of secondary CNS lymphoma due to systemic disease.
* Primary intraocular lymphoma (PIOL)/ Primary vitreoretinal lymphoma (PVRL), isolated cerebrospinal fluid (CSF) disease, or a relapsed or refractory PCNSL.
* Any significant medical condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she was to participate in the study based on investigator's judgement.
* History of another primary malignancy that has not been in remission for ≥2 years.

  a. Exceptions include certain adequately treated non-invasive malignancies, localized prostate cancer treated with curative intent, and completely resected Stage 1 solid tumors with a low risk of recurrence.
* Prior treatment with CAR T-cell or any other gene therapy product that utilizes human genome-editing technology.
* History of or active human immunodeficiency virus (HIV).
* Active hepatitis B or active hepatitis C.
* Active autoimmune disease requiring immunosuppressive therapy.
* History of prior allogeneic transplant, or solid organ transplant requiring immunosuppressive therapy.
* Other protocol-defined Inclusion/Exclusion criteria apply.