Pipeline

Why This Disease Focus?

• Primary central nervous lymphoma (PCNSL) is a rare, highly aggressive form of non-Hodgkin lymphoma confined in the brain, spinal cord, cerebrospinal fluid, and/or eyes.^1,2
• Although patients with PCNSL generally respond to guideline-recommended first-line high-dose methotrexate (HD-MTX) induction, up to 30% of patients have refractory disease and up to 45% relapse within 5 years.^3-5
• The prognosis for patients with relapsed or refractory (R/R) PCNSL is poor, with a median overall survival ranging from 5 to 20 months^6,7 and there are currently limited treatment options, with restricted access due to neurotoxicity.
• In PCNSL, acquired mutations lead to the constitutive activation of the B-cell receptor (BCR) and toll like receptor-4 (TLR), leading to excessive proliferation and survival of malignant B-cells.^8,9
• Bruton tyrosine kinase (BTK) is a pivotal mediator of the BCR-TLR signaling pathways, making it a promising therapeutic target.¹⁰

About This Program

Tirabrutinib is an irreversible, highly selective and potent second-generation BTK inhibitor, being investigated for the treatment of PCNSL. Tirabrutinib is currently being investigated in the PROSPECT Study, a Phase 2 study evaluating the safety and effectiveness of tirabrutinib as a monotherapy in R/R PCNSL (Part A), and in combination with one of two different HD-MTX-based regimes in newly diagnosed PCNSL (Part B).

Tirabrutinib is also being investigated in the IGNITE Study, a Phase 3 study evaluating the efficacy and safety of tirabrutinib monotherapy compared with rituximab and temozolomide (R-TMZ) combination therapy in patients with R/R PCNSL. 

Based on results from the PROSPECT study, a New Drug Application has been filed with the U.S. Food and Drug Administration. See news here.

To learn more about the PROSPECT study, click here. 

To learn more about the IGNITE study, click here.

References

¹ NCCN Guidelines for Patients®. Primary Central Nervous System Lymphoma; 2024. Accessed October 24, 2025. https://www.nccn.org/patients/guidelines/content/PDF/ pcnsl-patient.pdf

² Grommes C, et al. Neuro Oncol. 2019; 2(13): 296-305

³ Houillier C, et al. Neurobiology. 2020; 94(10) e1027-39

⁴ Langner-lermercier S, et al. Neuro Oncol. 2016-18(9):1297-303

⁵ Tringale KR, et al. Neuro Oncol. 2024; 26(11):2061-73

⁶ Volpini ME, et al. Curr Oncol. 2022;29(11):8160-70

⁷ Langner-Lemercier S, et al. Neuro Oncol. 2016;18(9):1297-303.

⁸ Wu J, et al. Ther Adv Hematol. 2024;15:20406207241259010

⁹ Xing Y, et al. Front Oncol. 2024;4:1463505

¹⁰ Rozkiewicz D, et al. Molecules. 2023;28(5):2400.