A Phase 2 Study Evaluating Epcoritamab in Subjects With Relapsed and Refractory Primary Diffuse Large B-cell Lymphoma of the CNS Treated With Lenalidomide and Rituximab
The purpose of this phase 2 study is to evaluate the efficacy and safety of epcoritamab in subjects with relapsed or refractory primary diffuse large B-cell lymphoma of the Central Nervous System treated with rituximab and lenalidomide.
• Subject (or their legally acceptable representative/trusted person) who understand and voluntarily signs and dates an informed consent form prior to any study-specific assessments/procedures being conducted.
• Subject ≥ 18 years old at the time of signing the informed consent form (ICF)
• Confirmed histology of primary diffuse large B-cell lymphoma of the CNS (according to the 2022 WHO classification) or confirmed cytology of primary vitreoretinal diffuse large B-cell lymphoma, with CD20 positivity in immunohistochemical staining or flow cytometry at any point in the disease history.
• Subjects with relapsed or refractory (R/R) PCNSL or PVRL after at least one line of systemic therapy. Subject with R/R PCNSL must have previously received at least high dose methotrexate. Subject with R/R PVRL must have received either intravenous high dose methotrexate or intraocular methotrexate (PVRL cohort). Subjects can have received radiotherapy or intensive chemotherapy with hematopoietic stem cell rescue as part of treatment of the PCNSL or PVRL.
• ECOG performance status 0 to 2.
• Estimated minimum life expectancy of ≥ 2 months.
• R/R PCNSL subjects with evaluable disease on brain MRI.
• Able to swallow capsules (stomach tube not allowed)
• Adequate hematopoietic function:
‣ Absolute neutrophil count of ≥ 1.0 G/L without G-CSF support for at least 7 days before screening
⁃ Platelet count of ≥ 50 G/L without platelet transfusion within 7 days before screening
⁃ Hemoglobin ≥ 8.0 g/dL without RBC transfusion within 7 days before screening
⁃ Adequate renal function: calculated by Cockcroft-Gault equation creatinine clearance \> 40 ml/min. Subjects with calculated creatinine clearance \> 40 and \< 60ml/min lenalidomide dose will be adjusted.
⁃ Adequate liver function: Serum total bilirubin level ≤ 2.0 mg/dl \[34 µmol/L\] (unless bilirubin rise is due to Gilbert's syndrome) and serum transaminases (AST or ALT) ≤ 3 upper normal limits.
⁃ Able to understand teratogenic risks of the treatment (Lenalidomide).
⁃ Women of childbearing potential (WOCBP) should agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting study treatment, 2) while participating in the study, 3) dose interruptions, and 4) for at least 12 months after the final dose of rituximab, or for at least 12 months after the final dose of epcoritamab, or for at least 28 days after the final dose of lenalidomide . WOCBP should also agree to abstain from breastfeeding during study participation and for at least 4 months after discontinuation of all study treatments.
⁃ WOCBP should have a negative serum (beta-hCG) pregnancy test at screening and a negative serum or urine pregnancy test before treatment administration on Day 1 of every cycle.
⁃ Women should agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire study, until 12 months after the last administration of study treatment.
⁃ Man who is sexually active with a female of reproductive potential and has not had a vasectomy should agree to use a highly effective / an acceptable method of birth control (ie, condom) and must agree not to donate sperm, until 28 days after the final dose of lenalidomide and/or until 12 months after the final dose of epcoritamab and rituximab.
⁃ Subject covered by any social security system (France).
⁃ Subject (or their legally acceptable representative/trusted person) who understands and speaks one of the country official languages unless local regulation authorizes independent translators.