Phase II PROSPECT trial: Tirabrutinib monotherapy in R/R PCNSL

Results from Part A of the open-label, phase II PROSPECT (NCT04947319) trial, evaluating tirabrutinib, a second-generation Bruton tyrosine kinase (BTK) inhibitor, in 48 adults with relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL), were published in Blood by Grommes et al. The primary endpoint was overall response rate (ORR). 

Key data: At a median follow-up of 11.5 months, the ORR was 67% (95% confidence interval [CI], 52–80) with a complete response (CR) rate of 44% (95% CI, 29–59). Median time-to-response (TTR) was 1.0 month, and median duration of response (DoR) was 9.3 months (95% CI, 4.6–14.6). Median disease-free survival (DFS) and progression-free survival (PFS) were 9.2 months (95% CI, 5.0–14.9) and 6.0 months (95% CI, 5.3–11.1), respectively; median overall survival (OS) was not reached (NR). Treatment-emergent adverse events (TEAEs) occurred in 98% of patients (Grade ≥3, 56%), with serious TEAEs in 44% of patients. The most frequently reported Grade ≥3 treatment-related TEAEs were neutropenia (8%) and maculopapular rash (6%). One treatment-related death was reported (bronchopulmonary aspergillosis).

Key learning: In Part A of the PROSPECT trial, tirabrutinib monotherapy demonstrated rapid, durable responses in adults with R/R PCNSL, supporting further investigation in the phase III IGNITE (NCT07104032) trial.