Phase 1 Trial of Orelabrutinib in Combination with Rituximab, Methotrexate, and Dexamethasone in Patients with Newly Diagnosed Primary CNS Lymphoma Implementing Bayesian Design for Dose-Seeking

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal subtype of non-Hodgkin's lymphoma (NHL). High-dose methotrexate (HD-MTX)-based regimens are the first-line treatment for PCNSL, but remain suboptimal due to response instability and short effective remission duration. Orelabrutinib is a novel, potent, highly selective BTK inhibitor with a high CSF concentration. This study aims to investigate optimal combination dose of Orelabrutinib in combination with Rituximab, Methotrexate, and Dexamethasone (ORMD) as well as safety and efficacy of the regimen.