IGNITE: a phase III study of tirabrutinib versus rituximab and temozolomide combination therapy in relapsed/refractory primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare, highly aggressive form of non-Hodgkin lymphoma. Although initial responses to the guideline-recommended first-line high-dose methotrexate induction treatment are high, some patients have refractory disease and most experience relapse. Approved therapies for relapsed or refractory (R/R) PCNSL are limited in the US, and there are none in Europe, creating an urgent unmet need for effective treatments. Tirabrutinib is a highly potent and selective second-generation Bruton tyrosine kinase inhibitor approved in Japan, Taiwan, and South Korea for patients with R/R PCNSL. Here, we describe the rationale and design of IGNITE (ONO-4059-17), an ongoing, phase III, multiregional, open-label, randomized study of tirabrutinib vs rituximab and temozolomide combination therapy in R/R PCNSL. The primary endpoint is progression-free survival based on blinded independent review committee (BIRC) per International PCNSL Collaborative Group (IPCG) criteria. Key secondary endpoints are overall response rate based on BIRC per IPCG criteria and overall survival. Safety will be assessed by the incidence and severity of treatment-emergent adverse events.Clinical trial registration: www.clinicaltrials.gov identifier is NCT07104032.