1. Written informed consent by the participant or legal authorized representative prior to Screening
2. Participants aged ≥18 years on the day of consenting to the study
3. Pathology report confirming the diagnosis of B-cell PCNSL
4. Relapsed or refractory B-cell PCNSL with at least 1 prior HD-MTX–based therapy for

PCNSL

• Relapsed disease: Patients who achieved a response (CR, CRu, PR) to the last treatment and subsequently experienced disease progression. Note: If response to prior therapy is unknown and prior therapy was concluded >90 days before progression was found, this will be viewed as relapsed disease.

• Refractory disease: Patients whose best response to the last treatment was stable disease or PD. Note: if response to prior therapy is unknown and prior therapy was concluded

≤90 days before progression was found, this will be viewed as refractory disease.

1. One or more bi-dimensionally measurable brain lesions with a minimum diameter

≥1 cm × ≥1 cm in gadolinium-enhanced MRI based on local read performed within 14 days before starting study drug

1. Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2 at Screening
2. Life expectancy of at least 3 months
3. Adequate bone marrow, renal, and hepatic function defined at Screening by the central laboratory as:

• Absolute neutrophil count ≥1000/mm3

• Platelets ≥100,000/mm3

• Hemoglobin ≥8.0 g/dL without packed red blood cell transfusion 14 days before starting study drug

• Total bilirubin ≤1.5 × upper limit of normal (ULN), except for participants with known Gilbert’s syndrome, who may have total serum bilirubin <3 × ULN

• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN

• Estimated glomerular filtration rate ≥30 mL/min/1.73 m2 × participant body surface area

(m2)/1.73 derived from the Chronic Kidney Disease Epidemiology Collaboration

1. Female participants of childbearing potential must meet ALL of the following requirements:

• Have a negative central serum (beta-human chorionic gonadotropin) β-hCG pregnancy test at Screening and a negative pregnancy test prior to the first dose of study drug on Cycle 1 Day 1

AND

• Agree to comply with the study defined contraceptive requirements as outlined in the protocol

1. Male participants must agree to comply with study defined contraceptive requirements as outlined in the protocol

1. Isolated intraocular PCNSL or spinal PCNSL with no brain lesions
2. Participants who have contraindications to MRI or use of MRI contrast
3. Participants with non-B cell PCNSL
4. Participants with systemic presence of lymphoma
5. Prior nitrosoureas (eg, carmustine) within 42 days, cytarabine and cytotoxic therapies other than procarbazine and methotrexate within 28 days, procarbazine within 21 days, methotrexate within 14 days before starting study drug
6. Prior non-cytotoxic investigational drugs (including bispecific antibodies) within 14 days or 5 half-lives, whichever is shorter, before starting study drug
7. Prior investigational cytotoxic drugs within 28 days or 5 half-lives, whichever is shorter, before starting study drug
8. Prior autologous stem cell transplant or CAR-T cell therapy within 1 month and allogeneic stem cell transplant within 6 months before starting study drug
9. Prior radiotherapy within 14 days before starting study drug
10. Prior major invasive surgery within 28 days before starting study drug, or minor invasive surgery within 7 days before starting study drug
11. Prior Bruton’s tyrosine kinase inhibitor treatment
12. Refractory to temozolomide with or without rituximab contain