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

Juno Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Lymphoma

Treatments: Drug: Fludarabine; Drug: Rituximab; Drug: Procarbazine; Drug: Methotrexate; Drug: Temozolomide; Drug: Calcium folinate; Drug: Cyclophosphamide; Biological: Liso-cel

Study type: Interventional

Funder types: Industry

Identifiers

NCT07015242

U1111-1318-3732 (Other Identifier)

2025-521144-38 (Other Identifier)

CA082-1215

2025

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and efficacy of lisocabtagene maraleucel (Breyanzi/liso-cel/BMS-986387) in adults as first-line treatment in transplant-ineligible Primary Central Nervous System Lymphoma (PCNSL).

Enrollment: 65 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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65 participants in 1 patient group

Liso-cel Administration

Experimental group

Treatment:

Biological: Liso-cel

Drug: Calcium folinate

Drug: Cyclophosphamide

Drug: Temozolomide

Drug: Methotrexate

Drug: Procarbazine

Drug: Rituximab

Drug: Fludarabine