CTNI-39. TIRABRUTINIB FOR THE TREATMENT OF RELAPSED OR REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA: EFFICACY AND SAFETY FROM THE PHASE II PROSPECT STUDY

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a rare non-Hodgkin lymphoma localized to the brain, cerebrospinal fluid, or eyes. Treatment options are limited and prognosis is poor, particularly in the relapsed or refractory (r/r) setting. Tirabrutinib, a second-generation Bruton’s tyrosine kinase inhibitor, is approved for PCNSL in Japan, Taiwan, and South Korea. There are no currently approved drug therapies for PCNSL in the US or Europe. Here we report results from the PROSPECT study (NCT04947319) conducted in the US. METHODS In this open-label phase II study, patients with r/r PCNSL received oral tirabrutinib 480 mg as monotherapy once daily. Primary endpoint was overall response rate (ORR) assessed by independent review committee. Secondary endpoints included duration of response (DOR), time to response (TTR), best overall response (BOR), and safety. Overall survival (OS) and progression-free survival (PFS) were exploratory endpoints. RESULTS Forty-eight patients were enrolled. Median age was 65.5 years. With median follow-up of 11.5 months as of November 1, 2024 (data cutoff), ORR was 67%, with a complete response rate (CRR: confirmed [CR] + unconfirmed [CRu]) of 44% and a partial response rate of 23%. Median DOR was 9.3 months; median TTR was 1.0 months. Median OS was not reached; median PFS was 6.0 months. Incidence of any-grade treatment-emergent adverse events (TEAEs) was 98% and of grade ≥3 was 56%. Any-grade treatment-related adverse events (TRAEs) were experienced by 75%; grade ≥3 TRAEs were experienced by 27%, most frequently neutrophil count decreased (8%) and maculo-papular rash (6%). At data cutoff, 27% of patients remain on treatment. Main reasons for discontinuation were disease progression (54%) and death (8%). CONCLUSIONS With ORR of 67%, CR/CRu rate of 44%, median DOR of 9.3 months, and manageable safety, the PROSPECT trial supports tirabrutinib monotherapy as a potentially effective treatment option for patients with r/r PCNSL.