NB02 (Poseltinib) Combined Rituximab and Lenalidomide in R/R PCNSL

Inclusion Criteria:

1. A patient who voluntarily decided to participate and provided written consent afterreceiving an explanation of this clinical trial and the characteristics of theinvestigational drug.

2. Adults aged 19 years or older and 80 years or younger.

3. Patients diagnosed histopathologically with CD20-positive primary central nervoussystem lymphoma (PCNSL).

4. Patients with confirmed disease progression or treatment resistance after remissioninduction therapy, radiotherapy, or autologous transplantation, with no more thantwo prior systemic treatments and no more than one prior radiotherapy treatment (preconditioning and transplantation for hematopoietic stem cells are counted as onesystemic treatment; radiotherapy, regardless of fractionation or dose, includingconcurrent chemoradiotherapy, is counted as one treatment).

5. Patients with measurable lesions identified by gadolinium-enhanced brain MRI (CT maybe used if MRI is contraindicated).

6. Patients with an ECOG Performance Status (PS) score of 2 or less.

7. Patients who agree to comply with the Pregnancy Prevention Plan (PPP) forlenalidomide.

8. Patients with an expected survival of at least 3 months, as judged by theinvestigator.

Exclusion Criteria:

1. Patients newly diagnosed with primary central nervous system lymphoma (PCNSL).

2. Patients with ocular lymphoma without brain lesions.

3. Patients with metastatic CNS lymphoma involving organs outside the central nervoussystem, except th eeyes and cerebrospinal fluid (if systemic disease is present:Secondary CNS lymphoma).

4. Patients whose screening laboratory test results meet the following criteria (⁕corrected after transfusion or use of hematopoietic growth factors are acceptable):

(1) Absolute neutrophil count <1,000/μL (at least 2 weeks after G-CSF administration).

(2) Platelet count <75,000/μL (at least 1 week after platelet transfusion). (3) Hemoglobin <9.0 g/dL (at least 2 weeks after red blood cell transfusion). (4) Serum calcium >12.0 mg/dL. (5) Serum creatinine >1.5 x the upper normal limit (UNL) or creatinine clearance <60 mL/min (based on the Cockcroft-Gault formula).

(6) Alanine aminotransferase (ALT) >3 × UNL. (7) Aspartate aminotransferase (AST) >3 × UNL. (8) Total bilirubin >1.5 × UNL (Gilbert syndrome: up to 3 × UNL).

• Patients with cardiovascular, hepatic, renal, neurological, immune, infectious, orpsychiatric disorders that could affect safety, trial evaluation, or protocolcompliance (e.g., regular visits).

5. The following heart conditions:

6. Symptomatic or uncontrolled angina and congestive heart failure.

7. Arrhythmias requiring medication (controlled cases with medication areallowed).

8. Clinically significant myocardial infarction within 6 months before trialparticipation.

9. History of thrombosis or embolism within 6 months before screening.

10. Gastrointestinal bleeding above Grade 2 according to CTCAE within 6 monthsbefore screening.

11. Ongoing infection above Grade 2 according to CTCAE at the time of screening.

12. Severe hepatic impairment (e.g., cirrhosis), chronic hepatitis with HBVreactivation.

• Patients with HBsAg (-) and HBcAb (-), or HBsAg (-) and HBcAb (+) withundetectable HBV DNA, can participate. Prophylactic antiviral therapy and HBVDNA monitoring (every 3-4 weeks) are required for HBcAb (+) cases withundetectable HBV DNA.

10. Uncontrolled hepatitis C virus (HCV) infection.

• Patients with negative HCV antibodies or undetectable HCV RNA can participatewith HCV RNA monitoring (every 1 cycle).

11. HIV infection. Patients with negative HIV antibodies or antigen-negativedespite HIV antibody positivity can participate.
12. Severe renal impairment requiring hemodialysis or hemofiltration atscreening.
13. Known immunodeficiency disorders.
14. Known autoimmune diseases (e.g., multiple sclerosis, acute disseminatedencephalomyelitis, rheumatoid arthritis).
15. History of severe cutaneous adverse reactions (SCARs), including erythemamultiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drugreaction with eosinophilia and systemic symptoms (DRESS), or acutegeneralized exanthematous pustulosis (AGEP).
16. History of malignancies other than the target disease, except:
17. No treatment for malignancy and disease-free for at least 5 years beforescreening.
18. Completely cured with no evidence of recurrence for malignancies within 5years if surgically treated (e.g., Stage I/II papillary or follicularthyroid cancer, basal cell/squamous cell carcinoma, cervical dysplasia orcarcinoma in situ, early-stage stomach or colorectal cancer).
19. Patients suspected of moderate dementia (K-MMSE-2 score ≤17).
20. Patients unable to take oral medication.
21. Hypersensitivity to study drugs (rituximab, lenalidomide, poseltinib) orexcipients.
22. Prior use of lenalidomide, poseltinib, or other BTK inhibitors.
23. Genetic disorders such as galactose intolerance, Lapp lactase deficiency,or glucose-galactose malabsorption.
24. Women who are pregnant or breastfeeding.
25. Women of childbearing potential⁕ and male participants with femalepartners of childbearing potential who do not agree to use two reliablecontraceptive methods at least 28 days before administration of theinvestigational drug, during the trial, during temporary discontinuation,and for 12 months after the last administration. (Complete abstinence fromheterosexual intercourse is an exception.)

• Women not of childbearing potential include those who have undergone hysterectomy orbilateral oophorectomy, or those in natural menopause for at least 24 consecutivemonths for non-disease reasons.

24. Male participants who do not agree to:

25. Use condoms during the study, even after vasectomy, during temporarydiscontinuation, and for 12 months after the last administration.

26. Avoid sperm/semen donation for 12 months after the study.

27. Immediately inform investigators if their partner becomes pregnant during thestudy or within 3 months after the study.

28. Patients with a history of substance abuse, medical, psychiatric, or socialconditions that could interfere with trial participation or results.

29. Patients unable to understand or comply with trial instructions or with ahistory of poor adherence to medical treatments.