Velexbru (tirabrutinib) / Ono Pharmaceutical, Gilead, Deciphera Pharmaceuticals - LARVOL DELTA

Trial in progress (IGNITE): a phase 3, multiregional, open-label, randomized study of tirabrutinib vs rituximab and temozolomide (R-TMZ) in participants with relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL) (SNO 2026) - No abstract available

Clinical • P3 data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma

Trial in Progress (IGNITE): A Phase 3, Multiregional, Open-Label, Randomized Study of Tirabrutinib vs Rituximab and Temozolomide in Relapsed/Refractory Primary Central Nervous System Lymphoma (SOHO 2026) - P2, P3 | "Other secondary endpoints include complete response rate, best overall response, time to response, time to complete response, duration of response, and disease-free survival, all by BIRC. Previously presented at ASH 2025, Orlando, FL, USA."

Clinical • P3 data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

Severe Central Nervous System Fungal Infection Following Tirabrutinib Administration in a Patient with Refractory Primary Central Nervous System Lymphoma: A Case Report. (PubMed, NMC Case Rep J) - "Despite treatment with high-dose methotrexate combined with rituximab, neurological symptoms rapidly deteriorated...We started treatment with voriconazole first, and then added amphotericin B, but multiple cerebral abscesses developed and progressed to encephalitis, resulting in death. Burton's tyrosine kinase is a gene crucial for the general antifungal immunity, and when using Burton's tyrosine kinase inhibitors, physician should always be mindful of preventing, detecting early, and addressing fungal infections to avoid fatal adverse events like in this case."

Journal • B Cell Lymphoma • CNS Disorders • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Liver Failure • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Oral Cancer • Primary Central Nervous System Lymphoma • Respiratory Diseases • Vasculitis • CD20

Interim Analysis Data from Multi-Center Retrospective Observational Study of Effectiveness, Safety, and Treatment Status of Tirabrutinib in 161 Japanese Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma: Rosetta Study (ASH 2024) - P, P=N/A | "Conclusion : These data demonstrate the effectiveness and safety of tirabrutinib in a large number of patients in clinical practice, and the findings are consistent with previous reports. These data indicate that tirabrutinib is a promising treatment option for r/r PCNSL."

Observational data • Retrospective data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Ophthalmology • Primary Central Nervous System Lymphoma • T Cell Non-Hodgkin Lymphoma

Tirabrutinib for the treatment of relapsed or refractory primary central nervous system lymphoma: Efficacy and safety from the phase II PROSPECT study. (ASCO 2025) - P2 | "With an ORR of 66.7%, CR/CRu rate of 43.8%, median DOR of 9.3 mo, and a manageable safety profile, the PROSPECT trial supports tirabrutinib monotherapy as a potentially effective treatment option for patients with r/r PCNSL."

Clinical • P2 data • Anemia • CNS Disorders • CNS Lymphoma • Dermatology • Epilepsy • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Primary Central Nervous System Lymphoma • Pruritus • Respiratory Diseases

TIRABRUTINIB FOR THE TREATMENT OF RELAPSED OR REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA: EFFICACY AND SAFETY FROM THE PHASE II PROSPECT STUDY (ICML 2025) - P2 | "With an ORR of 66.7%, CR/CRu rate of 43.8%, median DOR of 9.3 mo, and a manageable safety profile, the PROSPECT trial supports tirabrutinib monotherapy as a potentially effective treatment option for patients with r/r PCNSL. Keyword: molecular targeted therapies"

Clinical • P2 data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

INITIAL RESULTS FROM THE PRIZM+ PHASE II PLATFORM STUDY FOR RELAPSED AND REFRACTORY PRIMARY CNS LYMPHOMA: COHORT 1 ZANUBRUTINIB MONOTHERAPY (EHA 2024) - "Preliminary data in rrPCNSL withibrutinib and tirabrutinib demonstrate activity, however pharmacokinetic (PK) and translational data arelimited... We demonstrated feasibility of a prospective multicentre phase II platform clinical trial in PCNSL enrolling 23patients across 15 months in this challenging patient population, including patients with significantneurocognitive dysfunction who were consented via a legal representative. Primary endpoint data(investigator-assessed ORR) will be presented at the EHA meeting assuming the required number of patientsreach the 8 week imaging time-point as planned in the SAP. Combination therapy is planned for cohort 2within this platform protocol."

Monotherapy • P2 data • Bone Marrow Transplantation • CNS Lymphoma • Cognitive Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • MYD88

Timing of autologous stem cell transplantation and induction response in central nervous system lymphoma. (PubMed, Int J Hematol) - "Although high-dose busulfan and thiotepa (BuTT) conditioning followed by autologous stem cell transplantation (ASCT) is a promising consolidation strategy, the optimal timing and real-world outcomes of ASCT remain unclear...Nine patients underwent upfront ASCT shortly after achieving complete remission with rituximab, methotrexate, procarbazine, and vincristine and remained in remission at a median follow-up of 681 days (range, 147-1322 days)...BuTT/ASCT is highly effective when administered promptly after remission, whereas salvage ASCT after multiple therapies is associated with poor outcomes. Timely clinical decision-making and upfront consolidation may be key to optimizing the therapeutic benefits of ASCT in CNSL, although further validation is warranted."

Journal • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma • Transplantation

Velexbru: Launch in Japan for secondary central nervous system lymphoma in FY2026 (Ono Pharmaceuticals) - Q1 FY2026 Results

Launch Japan • CNS Tumor • Oncology • Secondary Central Nervous System Lymphoma

BRILLIANT: ONO-4059 Study in Patients With Steroid-resistant Pemphigus (clinicaltrials.gov) - P3 | N=34 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed

Ono Pharma Submits a Supplemental Application in Japan to Expand the Use of VELEXBRU Tablets for the Treatment of Central Nervous System Involvement (Newswire Today) - "This application is based on the results of a phase 2 investigator-initiated trial (NCCH2201/MK013 trial, the CRYSTAL trial) conducted at multiple centers in Japan, including the National Cancer Center Hospital, involving patients with relapsed or refractory secondary central nervous system lymphoma (SCNSL)....The results from this trial will be presented at the European Hematology Association (EHA) 2026 congress to be held in Stockholm, Sweden, from June 11 to June 14, 2026."

Japan filing • P2 data • Primary Central Nervous System Lymphoma

Potential role of tirabrutinib as part of an optimal treatment strategy for lymphomatosis cerebri: illustrative case. (PubMed, J Neurosurg Case Lessons) - "She underwent therapy with rituximab, methotrexate, procarbazine, and vincristine followed by high-dose cytarabine, achieving temporary remission; however, relapse occurred 1 month after consolidation therapy. This case also suggests a potential therapeutic role for tirabrutinib in early-relapsing LC. https://thejns.org/doi/10.3171/CASE26337."

Journal • B Cell Lymphoma • Brain Cancer • CNS Disorders • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Glioma • Hematological Malignancies • High Grade Glioma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Solid Tumor • B2M • CD20 • MYD88

TRIAL IN PROGRESS: A PHASE 3, MULTIREGIONAL, OPEN-LABEL, RANDOMIZED STUDY OF TIRABRUTINIB VS RITUXIMAB AND TEMOZOLOMIDE IN RELAPSED/REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (IGNITE) (EHA 2026) - P2, P3 | "Recommended treatment includes high-dose chemotherapy (HDC) ± autologous stem cell transplantation (ASCT), whole brain radiation therapy (WBRT), or better-tolerated regimens (temozolomide [TMZ] or lenalidomide ± rituximab [RTX], RTX, pomalidomide, ibrutinib, or pemetrexed)...Tumor response will be assessed at screening, C2D1, C3D1, then every 2 cycles through C25D1, and every 4 cycles thereafter per IPCG criteria. Previously presented at ASH 2025, Orlando, FL, USA."

Clinical • P3 data • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Pruritus

IGNITE: a phase III study of tirabrutinib versus rituximab and temozolomide combination therapy in relapsed/refractory primary central nervous system lymphoma. (PubMed, Future Oncol) - P3 | "Although initial responses to the guideline-recommended first-line high-dose methotrexate induction treatment are high, some patients have refractory disease and most experience relapse...Key secondary endpoints are overall response rate based on BIRC per IPCG criteria and overall survival. Safety will be assessed by the incidence and severity of treatment-emergent adverse events.Clinical trial registration: www.clinicaltrials.gov identifier is NCT07104032."

Journal • P3 data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

A Study to Investigate the Pharmacokinetics of Tirabrutinib in Participants With Mild, Moderate, and Severe Hepatic Impairment Compared to Healthy Participants (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Ono Pharmaceutical Co., Ltd. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2026 ➔ Apr 2026

Trial completion • Trial completion date • CNS Lymphoma • Hematological Malignancies • Hepatology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

ORELABRUTINIB IN PATIENTS WITH RELAPSED OR REFRACTORY PRIMARY OR SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA: A MULTICENTER, OPEN-LABEL, PHASE II STUDY (EHA 2026) - "Importantly, the observed PFS outcomes were comparable to those reported with tirabrutinib (median PFS 2.9 months), a BTK inhibitor approved in Japan for this indication. Patient demographics and baseline characteristics Characteristics 150mg QD(N=39) 200mg QD (N=22) ALL(N=61) Median age(Q1, Q3),years 56.9(50.9,66.0) 60.4(57.6,66.7) 57.9(52.5,66.0) Male,n(%) 20(51.3) 13(59.1) 33(54.1) ECOG,n(%) 0-1 21(53.8) 12(54.5) 33(54.1) ≥2 18(46.2) 10(45.5) 28(45.9) R/R PCNSL,n(%) 34(87.2) 22(100.0) 56(91.8) R/R SCNSL,n(%) 5(12.8) 0 5(8.2) Prior therapy,n(%) Radiotherapy 9(23.1) 6(27.3) 15(24.6) Surgical treatment for cancer 38(97.4) 18(81.8) 56(91.8) HCT-ASCT 1(2.6) 0 1(1.6) Summary/Conclusion Orelabrutinib monotherapy demonstrated preliminary antitumor activity and a manageable safety profile in patients with r/r PCNSL/SCNSL, a population with high unmet medical need. Its favorable blood-brain barrier penetration supports further investigation in CNS lymphomas."

Clinical • P2 data • CNS Lymphoma • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma

A multicenter randomized phase II/III trial of salvage treatment for refractory primary central nervous system lymphoma using tirabrutinib: JCOG2314 (ReSTART). (PubMed, Jpn J Clin Oncol) - "Patients refractory to high-dose methotrexate-based induction therapy have an extremely poor prognosis...A total of 94 patients from 49 institutions will be enrolled over 4 years. The trial has been registered in the Japan Registry of Clinical Trials (study number: jRCT1031250645)."

Journal • P2/3 data • Alzheimer's Disease • CNS Lymphoma • Cognitive Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

Impact of nasogastric administration using the simple suspension method on serum tirabrutinib levels: A case report. (PubMed, Am J Health Syst Pharm) - "Tirabrutinib concentrations may increase with nasogastric administration using the simple suspension method. In patients unable to ingest tablets orally, careful clinical monitoring is warranted, and therapeutic drug monitoring may be considered in select cases. The accumulation of further cases and pharmacokinetic investigations are warranted."

Journal • CNS Lymphoma • Gastrointestinal Disorder • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

REAL-WORLD DURABLE CLINICAL BENEFITS OF TIRABRUTINIB AND ITS SAFETY PROFILE IN RELAPSED OR REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA: INTERIM ANALYSIS FROM THE REVEAL STUDY (EHA 2026) - P | "Summary/Conclusion Tirabrutinib provides rapid and durable treatment responses over a 10.9-month follow-up period in r/r PCNSL patients. These results, along with high cumulative durability and a consistent safety profile, support its role as a key targeted therapy in real-world clinical practice in Taiwan."

Clinical • Real-world • Real-world evidence • Cardiovascular • CNS Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Nephrology • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma

EFFICACY AND SAFETY OF TIRABRUTINIB FOR RELAPSED OR REFRACTORY SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA: RESULTS OF THE PHASE II CRYSTAL/NCCH2201 STUDY (EHA 2026) - P | "Summary/Conclusion Tirabrutinib demonstrated clinically meaningful activity with a manageable safety profile in heavily pretreated patients with R/R SCNSL. The phase II CRYSTAL/NCCH2201 study supports tirabrutinib as a promising therapeutic option for this disease with extremely poor prognosis."

Clinical • P2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Pruritus • Secondary Central Nervous System Lymphoma • Thrombocytopenia • CD79B • MYD88

PLCG2 Exon-Skipped Variants: Insights into Their Potential Role in Chronic Lymphocytic Leukemia. (PubMed, Blood Adv) - "In our study, REC-1 cells that acquired resistance to BTKi tirabrutinib by long-term treatment gained a splice-site mutation (SSM) c.2236-1G>T in PLCG2. Expression analysis in CLL cells isolated from patients before and after targeted treatments revealed a decrease in expression of ∆20-22 post-venetoclax (p = 0.02)while no change in expression was observed after ibrutinib treatment, indicating that these variants may persist in the presence of ibrutinib but might be lost in the absence of drug selection pressure. Our study reveals novel PLCG2 splice-site alterations and exon-skipped variants beyond the classical BTK or PLCG2 mutations, to have a potential role in BTKi resistance and inform treatment selection."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PLCG2

Multifunctional Nanoplatform for Synergistic Cancer Therapy via Enhanced Immunogenic Cell Death and Immune Modulation. (PubMed, ACS Appl Mater Interfaces) - "Additionally, the drug Tirabrutinib (Tir) could suppress activity of Bruton's tyrosine kinase (BTK) and alleviate the immunosuppressive tumor microenvironment...The in vitro and in vivo investigation verified that the ZPMTH could restrain the proliferation of primary and contralateral rechallenge tumor model with satisfactory effectiveness. Therefore, ZPMTH provided a promising approach for introducing ICD nanoinducer into antitumor immunotherapy for synergistic cancer therapy."

Journal • Immune Modulation • Immunology • Oncology • BTK

More than an attachment module: covalent inhibitor warheads influence BTK dynamics and function. (PubMed, bioRxiv) - "Treatment of B-cell cancers such as Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma has been revolutionized by the development of covalent inhibitors that target Bruton's Tyrosine Kinase (BTK). These orally bioavailable cancer drugs are highly effective in interfering with B-cell growth and provide patients with long lasting remission. These treatments do come with vulnerabilities as inhibitor-specific resistance mutations emerge in a subset of patients. Here we investigate how chemical differences among available BTK inhibitors drive differential protein dynamics and signaling interactions that could foreshadow specific resistance mechanisms. As continuous use of BTK inhibitors progresses in time, the field will continue to learn which drugs, and which structural features of these drugs, either limit resistance or provide alternatives to established resistance."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology

ONO-4059-17: Study of Tirabrutinib vs Rituximab/Temozolomide for Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) (clinicaltrialsregister.eu) - P2/3 | N=6 | Not yet recruiting | Sponsor: Deciphera Pharmaceuticals Inc.

New P2/3 trial • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

REVEAL: Real-World Evidence of Effectiveness and Safety of Tirabrutinib in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma in Taiwan: A Nationwide Study (clinicaltrials.gov) - P=N/A | N=24 | Completed | Sponsor: Ono Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Completed | N=35 ➔ 24 | Trial completion date: Dec 2026 ➔ Mar 2026 | Trial primary completion date: Dec 2026 ➔ Mar 2026

Enrollment change • HEOR • Real-world evidence • Trial completion • Trial completion date • Trial primary completion date • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma