Velexbru (tirabrutinib) / Ono Pharma, Gilead - LARVOL DELTA

Trial in progress: A phase 3, multi-regional, open-label, randomized study of tirabrutinib vs rituximab and temozolomide in participants with Relapsed/Refractory primary central nervous system lymphoma (ASH 2025) - P2, P3 | "No approved therapies for relapsedor refractory (r/r) disease exist in the US or EU, and NCCN guideline-recommended treatment optionsbased on small studies can be divided into high-dose chemotherapy (HDC) with or without autologousstem cell transplantation (ASCT), whole brain radiation therapy (WBRT), or treatment with better-tolerated regimens such as temozolomide (TMZ) or lenalidomide with or without rituximab (RTX), RTX,pomalidomide, ibrutinib, or pemetrexed...Tumor response assessment will be performed at screening, C2D1, C3D1, thenevery 2 cycles through C25D1, and every 4 cycles thereafter according to IPCG criteria. ClinicalTrials.govregistration number: NCT07104032."

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

Outcomes and Treatment Sequences of Therapies with BCL2- and BTK Inhibitors in Chronic Lymphocytic Leukemia (CLL): An Analysis of Patient Data within the German CLL Study Group (GCLLSG) Registry (ASH 2023) - "We here present real-world data from the German CLL Study Group (GCLLSG) registry and report outcomes and treatment sequences of pts treated with either BCL2i (venetoclax) or BTKi (acalabrutinib, ibrutinib, spebrutinib, tirabrutinib, or zanubrutinib) as first administered targeted agent. EFS, TTNT and OS were comparable following Ven versus BTKi-based therapy in pts documented in the GCLLSG registry between 2014 and 2023."

Clinical • IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • IGH • TP53

Inhibition of Lysine Acetyltransferases p300/CBP Overcomes BTK Inhibitor Resistance in Mantle Cell Lymphoma Cells (ASH 2023) - "We compared three BTKis, ibrutinib, acalabrutinib and tirabrutinib, using DMSO as a control...This effect was even greater than that of existing drugs, including venetoclax (a BCL-2 inhibitor), and idelalisib (a PI3K inhibitor), which are thought to have synergistic effects... Our CRISPR screen identified lysine acetyltransferases p300/CBP as BTK inhibitor resistance genes in human MCL cells. The combination of a p300/CBP inhibitor and a BTK inhibitor synergistically suppresses both BTK and AKT, leading to NFκB suppression. Taken together, we first identified that the combination of p300/CBP inhibition and BTK inhibition could be a promising strategy for treating patients with MCL."

IO biomarker • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • NFKBIA • PLCG2

Tirabrutinib for the treatment of relapsed or refractory primary central nervous system lymphoma: efficacy and safety from the phase II PROSPECT study (SNO 2025) - P2 | "With ORR of 67%, CR/CRu rate of 44%, median DOR of 9.3 months, and manageable safety, the PROSPECT trial supports tirabrutinib monotherapy as a potentially effective treatment option for patients with r/r PCNSL."

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

Patient backgrounds associated with the prolonged effectiveness of tirabrutinib in patients with relapsed or refractory primary central nervous system lymphoma: Results from the ROSETTA study (SNO 2025) - P=N/A | "Additionally, the median rwPFS was numerically longer in patients with an interval of ≥1 year from the end of previous treatment to the start of tirabrutinib treatment (n = 46) than in patients with the interval of <1 year (n = 89; 15.6 vs 11.0 months), with a HR of 0.75 (<1 vs ≥1; 95% CI, 0.45–1.24). Conclusion : These data showed a tendency for prolonged rwPFS in patients with one prior treatment, a baseline KPS score of ≥50, or the interval of ≥1 year prior to the start of tirabrutinib treatment."

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

Tirabrutinib Therapy for Refractory or Relapsed Primary Central Nervous System Lymphoma: A Retrospective Analysis of 13 Cases (SNO 2025) - "Our findings suggest that tirabrutinib offers favorable efficacy and acceptable safety for refractory or relapsed PCNSL. It may be a viable option even for treatment-resistant and EBV-associated cases, potentially contributing to improved prognosis. Further accumulation of cases and prospective studies are warranted."

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

Tirabrutinib-anthracycline interactions in the brain tumor microenvironment: a focus on metabolic inactivation and resistance. (PubMed, Expert Opin Drug Metab Toxicol) - "Our in vitro data demonstrate that tirabrutinib influences daunorubicin pharmacodynamics by targeting both metabolic and transport pathways. However, Chou - Talalay analysis highlights the importance of appropriate dosing to achieve therapeutic synergy in combination regimens."

Biomarker • Journal • Brain Cancer • Oncology • Solid Tumor • AKR1C3

Tirabrutinib for the treatment of relapsed or refractory primary central nervous system lymphoma: efficacy and safety from the phase II PROSPECT study (WFNOS 2025) - P2 | "With ORR of 67%, CR/CRu rate of 44%, median DOR of 9.3 months, and manageable safety, the PROSPECT trial supports tirabrutinib monotherapy as a potentially effective treatment option for patients with r/r PCNSL."

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

Patient backgrounds associated with the prolonged effectiveness of tirabrutinib in patients with relapsed or refractory primary central nervous system lymphoma: Results from the ROSETTA study (WFNOS 2025) - P=N/A | "Additionally, the median rwPFS was numerically longer in patients with an interval of ≥1 year from the end of previous treatment to the start of tirabrutinib treatment (n = 46) than in patients with the interval of <1 year (n = 89; 15.6 vs 11.0 months), with a HR of 0.75 (<1 vs ≥1; 95% CI, 0.45–1.24). Conclusion : These data showed a tendency for prolonged rwPFS in patients with one prior treatment, a baseline KPS score of ≥50, or the interval of ≥1 year prior to the start of tirabrutinib treatment."

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

Tirabrutinib Therapy for Refractory or Relapsed Primary Central Nervous System Lymphoma: A Retrospective Analysis of 13 Cases (WFNOS 2025) - "Our findings suggest that tirabrutinib offers favorable efficacy and acceptable safety for refractory or relapsed PCNSL. It may be a viable option even for treatment-resistant and EBV-associated cases, potentially contributing to improved prognosis. Further accumulation of cases and prospective studies are warranted."

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

Primary spinal cord malignant B-cell lymphoma successfully treated with tirabrutinib at relapse: a case report. (PubMed, Eur Spine J) - No abstract available

Journal • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ONO-7018, a First-in-Class MALT1 Inhibitor, Provides Novel Therapeutic Strategies for B Cell Malignancies: Overcoming BTK Inhibitor Acquired Resistance and Enhancing the Antitumor Effect of BTK Inhibitors (ASH 2023) - P1 | "For example, BTK C481S mutation is well known as a resistant mutation to covalent BTK inhibitors and several mutations of BTK (such as T474I and L528W mutation) have recently been reported in relapsed or refractory CLL patients with acquired resistance to pirtobrutinib, a non-covalent BTK inhibitor...ONO-7018 and tirabrutinib were orally administered to the mice twice a day... ONO-7018 would provide novel therapeutic strategies to overcome the BTK inhibitor acquired resistance and enhance the antitumor effect of BTK inhibitors in clinic. Phase 1 study of ONO-7018 (NCT05515406) is currently ongoing."

Preclinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IRF4 • MALT1 • PLCG2

Gene Panels for Intraocular Lymphoma Can Overcome Diagnostic Difficulties and Enable Precision Medicine (ASH 2023) - "Our panel enables rapid and accurate diagnosis of IOL with only a small sample of intraocular liquid. We believe that this multiplex gene panel testing may aid in the diagnosis of IOL in difficult-to-diagnose patients, including those with chronic uveitis, by preventing CNS invasion due to diagnostic delay. Moreover, genetic profiling panels of IOL can help to stratify clinical outcomes.CD79B and BTG2 mutation is a potent predictive marker for relapse."

CNS Lymphoma • Eye Cancer • Hematological Malignancies • Lymphoma • Ocular Inflammation • Oncology • Ophthalmology • Uveitis • BTG2 • CD79B • MYD88 • PIM1

Post-Hoc Analysis of the Final, Three-Year Follow-up Results of a Phase I/II Study on Tirabrutinib (ONO-4059) in Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma (ASH 2023) - "TIR responses were observed in all patient subpopulations, and the baseline KPS was suggested to be associated with long-term response. KPS and QoL were generally maintained during the long-term observation period."

Clinical • P1/2 data • Retrospective data • Bone Marrow Transplantation • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Transplantation • CD79B • MYD88

A Case of IgM-Type Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits Developing During the Course of Lymphoplasmacytic Lymphoma (KIDNEY WEEK 2025) - "We report a case of IgM-type PGNMID associated with lymphoplasmacytic lymphoma (LPL) which progressed and developed nephrotic syndrome despite sustained serologic remission with tirabrutinib, necessitating a repeat kidney biopsy. Case Description A 72-year-old male patient with a 14-year history of LPL underwent treatment with corticosteroids and rituximab, yet exhibited a suboptimal therapeutic response...IgM-type PGNMID is associated with a poor kidney prognosis, with a median kidney survival of 44 months, which is consistent with this case. Retrospectively, despite the achievement of serologic remission, the deterioration in kidney function may have warranted consideration of subsequent treatment strategies, such as the use of proteasome inhibitors or B-cell lymphoma-2 inhibitors."

Clinical • B Cell Lymphoma • Fibrosis • Glomerulonephritis • Immunology • Lupus Nephritis • Lymphoma • Lymphoplasmacytic Lymphoma • Monoclonal Gammopathy • Nephrology • Renal Disease • Waldenstrom Macroglobulinemia • BCL2

Real World Evidence of Tirabrutinib As a Salvage Treatment in Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma in Taiwan: A Multicenter Study (ASH 2024) - "Infection remains a significant safety concern, although dermatological ADRs were less prevalent compared to clinical trials. With optimal prophylaxis, the risk of HBV reactivation was not a major concern."

Clinical • HEOR • Real-world • Real-world evidence • Atrial Fibrillation • Brain Cancer • Cardiovascular • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Hepatitis B • Hepatology • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Septic Shock • Solid Tumor • Thrombocytopenia

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 (WFNOS 2025) - P2 | "With ORR of 67%, CR/CRu rate of 44%, median DOR of 9.3 months, and manageable safety, the PROSPECT trial supports tirabrutinib monotherapy as a potentially effective treatment option for patients with r/r PCNSL."

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

Patient backgrounds associated with the prolonged effectiveness of tirabrutinib in patients with relapsed or refractory primary central nervous system lymphoma: Results from the ROSETTA study (WFNOS 2025) - P=N/A | "These data showed a tendency for prolonged rwPFS in patients with one prior treatment, a baseline KPS score of ≥50, or the interval of ≥1 year prior to the start of tirabrutinib treatment."

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

Comparison of One-Year Adverse Events Between First- and Second-Generation Bruton's Tyrosine Kinase Inhibitors: A Retrospective Study. (PubMed, Cureus) - "All BTKi agents were associated with bone marrow suppression, infection, and bleeding, whereas cardiac-related AEs occurred only with IBR. Several Grade 3 or higher events were identified, underscoring the need for careful monitoring of patients receiving BTKi in clinical practice."

Adverse events • Journal • Retrospective data • Cardiovascular • Hematological Malignancies • Infectious Disease

Plain language summary about tirabrutinib in relapsed/refractory primary central nervous system lymphoma. (PubMed, Future Oncol) - No abstract available

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

Bing-Neel Syndrome in Waldenström Macroglobulinemia: Updates on Clinical Management and BTK Inhibitor Efficacy. (PubMed, Cancers (Basel)) - "Historically, high-dose methotrexate- or cytarabine-based chemotherapy, intrathecal therapy, and radiotherapy have been used; however, responses varied, and toxicity was considerable...Retrospective data support durable responses with ibrutinib, tirabrutinib, and zanubrutinib, while early findings suggest that non-covalent BTK inhibitors expand options for relapsed or refractory cases. Herein, we synthesize current evidence on epidemiology, pathophysiology, and diagnostic work-up. We also outline therapeutic recommendations integrating the genotype, disease pattern, and patient fitness and conclude with unmet needs and future directions."

Journal • Review • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • MYD88

Study of Tirabrutinib (ONO-4059) in Patients With Primary Central Nervous System Lymphoma (PROSPECT Study) (clinicaltrials.gov) - P2 | N=119 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • 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=32 | Recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Not yet recruiting ➔ Recruiting | N=24 ➔ 32 | Initiation date: Jan 2026 ➔ Oct 2025

Enrollment change • Enrollment open • Trial initiation date • CNS Lymphoma • Hematological Malignancies • Hepatology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

A retrospective study of the BTK-inhibitor tirabrutinib for the treatment of recurrent/refractory primary CNS lymphoma (EANO 2025) - "In real-world settings, tirabrutinib has shown to be an effective and well-tolerated treatment for recurrent or refractory PCNSL."

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