Study of Epcoritamab in R/R Primary Diffuse Large B-cell Lymphoma of the CNS Treated With Lenalidomide and Rituximab

Exclusion Criteria

• •Subject who meets any of the following criteria should be excluded from enrollment in the study:
• •1. T-cell lymphoma.
• •2. Cerebral localization of a systemic lymphoma.
• •3. Prior history of organ transplantation or other cause of severe immunodeficiency.
• •4. Known Human Immunodeficiency Virus (HIV) or Positive HTLV1 serology.
• •5. Active Hepatitis B Virus (HBV) infection (DNA PCR-positive) or active hepatitis C Virus (HCV) infection (RNA PCR-positive). Subjects with evidence of prior HBV infection but who are PCR-negative are permitted in the study but should receive prophylactic antiviral therapy. Subjects who received treatment for HCV infection that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable.
• •6. Persistent SARS-CoV-2 infection. Subjects who have had or currently have a SARS-CoV-2 infection must demonstrate symptom resolution and provide a negative nasopharyngeal PCR test at time of inclusion. Both of these requirements must be met for the subject to be considered clear of the virus.
• •7. Impossibility to follow the calendar of exams because of geographic, social, or psychological reasons.
• •8. Active malignancy other than the one treated in this Study. Prior history of malignancies (other than inclusion diagnosis) unless the subject has been free of the disease for ≥ 2 years. However, subjects with the following history/concurrent conditions are allowed:
• •1. Non-invasive basal cell or epidermoid carcinoma
• •2. In situ Carcinoma of the cervix
• •3. In situ Carcinoma of the breast
• •4. Non-invasive, superficial bladder cancer
• •5. Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor, nodes, metastasis \[TNM\] clinical staging system
• •6. Any curable cancer with a complete response of \>2 years duration
• •9. Known or suspected hypersensitivity to the active substance or to any of the excipients.
• •10. Any previous treatment with CAR-T therapy within 30 days prior to enrollment.
• •11. Receiving immunosuppressive therapy, including more than the equivalent of 20 mg of prednisolone daily, unless for control of lymphoma or intermittent prophylaxis/treatment of allergic reactions.
• •12. Any previous treatment with a bispecific antibody targeting CD3 and CD20 and/or with lenalidomide, regardless of the time and duration.
• •13. Seizure disorder requiring anti-epileptic therapy unless related to lymphoma.
• •14. Vaccination with live, attenuated vaccines within 28 days prior of enrollment (except severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine). Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Experimental and/or non-authorized SARS-CoV-2 vaccinations are not allowed.
• •15. Use of any standard or experimental anti-cancer drug therapy within 28 days of the start (Day 1) of study treatment.
• •16. Major surgery within 4 weeks prior to enrollment
• •17. Clinically significant cardiovascular disease, including:
• •1. Myocardial infarction within 1 year prior to enrollment, or unstable or uncontrol disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV) cardiac arrhythmia (CTCAE Version 5.0 Grade 2 or higher), or clinically significant ECG abnormalities.
• •2. Stroke within 6 months prior to enrollment.
• •18. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) \>470 msec.
• •19. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment at time of enrollment.
• •20. Contraindication to all uric acid lowering agents.
• •21. Clinically significant liver disease, including active hepatitis, current alcohol abuse, or cirrhosis.
• •22. Active tuberculosis or history of treatment for active tuberculosis within the past 12 months.
• •23. Receiving immunostimulatory agent.
• •24. Prior allogeneic hematopoietic stem cell transplantation.
• •25. Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator's decision).
• •26. Subject deprived of his/her liberty by a judicial or administrative decision.
• •27. Subject hospitalized without consent.
• •28. Adult subject under legal protection.