Dr Nayak on Findings From the PROSPECT Trial of Tirabrutinib in Relapsed/Refractory PCNSL

"The earliest response was obtained at 1 month. This is very important for our relapsed/refractory patient population, because these patients are progressing neurologically and declining neurologically quite quickly."

Lakshmi Nayak, MD, director, Center for Central Nervous System (CNS) Lymphoma, senior physician, Dana-Farber Cancer Institute; and associate professor, neurology, Harvard Medical School, shared efficacy and safety data from the phase 2 PROSPECT trial (NCT04947319), which evaluated the second-generation BTK inhibitor tirabrutinib (Velexbru) in primary central nervous system lymphoma (PCNSL).

Findings presented at the 2025 Society for Neuro-Oncology Annual Meeting demonstrated strong efficacy with tirabrutinib, Nayak reported. At a data cutoff of November 1, 2024, and a median follow-up of 11.5 months, the overall response rate was 67%, including a complete response rate of 44%.

Nayak also emphasized the importance of the rapid onset of responses observed in the trial, noting that the earliest response with tirabrutinib was obtained at 1 month. This is considered a critical advantage with the drug for this patient population, as patients with relapsed/refractory disease often experience rapid neurological progression and decline, she said.

Moreover, the regimen demonstrated robust durability of response; the median duration of response was 9.3 months, and the median time to response was 1.0 month. The median progression-free survival (PFS) was 6 months, and the median overall survival was not reached, Nayak added.

Overall, the efficacy signal with tirabrutinib as monotherapy in this difficult-to-treat setting is considered very good, with both robust durability and favorable median PFS, Nayak emphasized. Regarding safety, the drug was very well tolerated with limited adverse effects, all of which were quite manageable, she stated.