In short
Tirabrutinib is an investigational Bruton's tyrosine kinase (BTK) inhibitor being studied for relapsed or refractory primary central nervous system lymphoma (PCNSL). One Phase 3 trial (NCT07104032) is comparing tirabrutinib monotherapy against rituximab plus temozolomide in 136 participants. The study is currently authorised but not yet recruiting.
Key points
- Tirabrutinib is a Bruton's tyrosine kinase (BTK) inhibitor, a type of targeted cancer therapy.
- The only registered trial is a Phase 3 study in relapsed or refractory primary central nervous system lymphoma.
- The trial plans to enroll 136 participants and is currently authorised.
- Tirabrutinib is given orally at 480 mg in the trial.
- The main measure is progression-free survival (PFS), assessed by an independent review committee.
What is tirabrutinib?
Tirabrutinib, also known by the development code GS-4059 or ONO-4059 and the trade name Velexbru, is a small-molecule drug classified as a Bruton's tyrosine kinase (BTK) inhibitor. It belongs to the antineoplastic class of medicines, specifically the protein kinase inhibitor group, and carries the ATC code L01EL06. In Japan, tirabrutinib hydrochloride is approved as a new active ingredient. The substance is also known by its full chemical name tirabrutinib hydrochloride.
How does tirabrutinib work?
Tirabrutinib works by blocking Bruton's tyrosine kinase (BTK), an enzyme that plays a key role in the growth and survival of B cells, a type of white blood cell. By inhibiting BTK, tirabrutinib interferes with B cell receptor signalling, which is important for the survival of malignant B cells in lymphomas. BTK inhibitors like tirabrutinib have been evaluated for their ability to cross the blood-brain barrier and reach tumours in the central nervous system, which is relevant for conditions such as primary central nervous system lymphoma.
Which conditions is tirabrutinib studied for?
- Relapsed or refractory primary central nervous system lymphoma (PCNSL) — a rare type of non-Hodgkin lymphoma that starts in the brain, spinal cord, or eyes and has come back after or not responded to previous treatment.
How is tirabrutinib given?
In the registered trial, tirabrutinib is administered orally at a dose of 480 mg. The comparison arm includes rituximab given by intravenous infusion at 375 mg/m² and temozolomide given orally at 200 mg/m².
What do the clinical trials show?
One Phase 3 trial (NCT07104032) is registered to compare tirabrutinib monotherapy against rituximab plus temozolomide in people with relapsed or refractory primary central nervous system lymphoma. The study plans to enroll 136 participants and is currently authorised, meaning it has received regulatory approval to begin but is not yet recruiting. The primary outcome is progression-free survival (PFS), defined as the time from randomisation to progressive disease or death from any cause, whichever occurs first, as assessed by a blinded Independent Review Committee using International Primary Central Nervous System Lymphoma Collaborative Group (IPCG) criteria.
What side effects are known?
The supplementary sources provided do not include a specific list of side effects for tirabrutinib in the context of this page. The trial record itself does not report adverse event data, as the study is not yet recruiting.