Brukinsa (zanubrutinib) / BeOne Medicines, Medison - LARVOL DELTA

A Study to Investigate the Relative Bioavailability and Food Effect of a Fixed-Dose Combination Tablet Containing Zanubrutinib and Sonrotoclax (BG-71332) in Healthy Adults (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: BeOne Medicines | Active, not recruiting ➔ Completed

Trial completion

MAZ-01: Zanubritnib and anti-MAG neuropathy (clinicaltrialsregister.eu) - P1/2 | N=50 | Recruiting | Sponsor: Azienda Ospedaliera di Padova | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Monoclonal Gammopathy • Non-Hodgkin’s Lymphoma • Oncology • Pain • Waldenstrom Macroglobulinemia

Cardiac Safety Profiles of First-Generation vs. Second-Generation BTK Inhibitors: A Meta-Analysis. (PubMed, Oncologist) - "Second-generation BTKi may provide a more favorable cardiovascular safety profile than ibrutinib, resulting in fewer key cardiac events and less treatment-limiting toxicity. These findings should inform clinical decision-making, especially for patients with increased risk for cardiovascular disease."

Journal • Retrospective data • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Oncology

ROSEWOOD: A Phase II Randomized Study of Zanubrutinib Plus Obinutuzumab Versus Obinutuzumab Monotherapy in Patients With Relapsed or Refractory Follicular Lymphoma. (PubMed, J Clin Oncol) - "The combination of ZO met its primary endpoint of a superior ORR versus O, and demonstrated meaningful activity and a manageable safety profile in patients with R/R FL. ZO had a favorable benefit-risk profile compared with O, and represents a potential combination therapy for patients with R/R FL."

Journal • Monotherapy • P2 data • Atrial Fibrillation • Cardiovascular • Fatigue • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Oncology • Thrombocytopenia

Combination of zanubrutinib (zanu) + venetoclax (ven) for treatment-naive (TN) CLL/SLL: Results in SEQUOIA arm D. (ASCO 2025) - P3 | "Funded by BeiGene Clinical Trial Registration Number: NCT03336333 Background: Zanu monotherapy demonstrated superior progression-free survival (PFS) compared with bendamustine + rituximab in patients (pts) without del(17p) at 26.2-month follow-up and sustained PFS benefit at 5-year follow-up. SEQUOIA arm D data demonstrate promising efficacy and tolerability of zanu + ven combination treatment in TN CLL/SLL, regardless of del(17p) and/or TP53 mutation status. The safety profile of zanu + ven was consistent with results of prior zanu studies, and no new safety signals were identified."

B Cell Lymphoma • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hypertension • Infectious Disease • Neutropenia • Small Lymphocytic Lymphoma • BCL2 • IGH

Zanubrutinib is well tolerated and effective in CLL/SLL patients intolerant of ibrutinib/acalabrutinib: Updated results. (PubMed, Blood Adv) - P2 | "These data demonstrate that patients intolerant of ibrutinib/acalabrutinib may benefit from switching to zanubrutinib therapy. ClinicalTrials.gov: NCT04116437."

Journal • Chronic Lymphocytic Leukemia • Fatigue • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Small Lymphocytic Lymphoma

Outcomes following transition from ibrutinib to zanubrutinib in patients with Waldenström macroglobulinemia from ASPEN. (PubMed, Blood Adv) - P3 | "Long-term follow-up is ongoing. Registration: NCT03053440, NCT04170283."

Journal • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Oncology • Waldenstrom Macroglobulinemia • MYD88

Zanubrutinib + venetoclax for treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including patients with del(17p) and/or TP53 mutation and unmutated immunoglobulin heavy-chain variable status: 3-year results from SEQUOIA arm D (ASH 2025) - P3 | "With extended FU of SEQUOIA Arm D, zanu+ven combo demonstrated robust efficacy and amanageable safety profile in TN CLL/SLL. Durable MRD responses were maintained across genomicsubgroups, including those with high-risk features. These data support the potential benefit of thisregimen in TN CLL/SLL regardless of del(17p), TP53 mutation, or IGHV status."

Clinical • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • IGH • TP53

Sonic: Escalated inpatient ramp-up of sonrotoclax in CLL/SLL and MCL (ASH 2025) - P2 | "Sonrotoclax (BGB-11417) is apromising next generation Bcl-2 inhibitor with better potency and specificity than venetoclax, a firstgeneration Bcl-2 inhibitor, in pre-clinical studies...Patients with a prior othermalignancy within the past 2 years are excluded.Objectives:Primary Objectives:To examine the safety and tolerability of an escalated ramp-up of sonrotoclax (BGB-11417) followinginitial debulking with zanubrutinib or rituximab in patients with treatment-naïve or R/R CLL/SLL andpatients with R/R MCL.To assess safety by measuring the frequency of adverse events (AEs), including episodes of laboratoryand clinical TLS.To evaluate the feasibility of reaching a target dose of sonrotoclax 320mg daily on day 12 +/- 2 daysfollowing a 4-day inpatient ramp-up of sonrotoclax.Secondary Objective:To estimate the efficacy of an escalated ramp-up of sonrotoclax followed by 1 year of combinationtherapy (with either zanubrutinib or rituximab) by assessing the overall..."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma

Precision targeting of BTK in chronic lymphocytic leukemia: computational insights into structural dynamics and the influence of mutations on BTK inhibitors through QM and MM studies. (PubMed, J Biomol Struct Dyn) - "Density functional theory-based local and global reactivity descriptors identified nucleophilic and electrophilic hotspots within the inhibitors, with nitrogen atoms in pirtobrutinib, zanubrutinib, and spebrutinib displaying pronounced nucleophilic potential, suggesting a key role in stabilizing interactions within the BTK active site. Molecular docking analyses revealed that these inhibitors maintained strong binding affinities across multiple BTK mutants, frequently exceeding that of ibrutinib...Binding free-energy calculations further supported these observations, with several mutant complexes demonstrating enhanced affinities relative to the wild type. Collectively, these findings highlight structurally resilient inhibitors capable of overcoming compound mutation-driven resistance and underscore the importance of BTK mutational profiling in guiding precision therapeutic strategies for BTK-driven malignancies."

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

Brukinsa: Expiry of patents in US/EU/China/Japan related to composition-of-matter in 2034 (BeOne Medicines) - Annual Report 2025: SPC in France, Germany, Italy, Spain and the UK until 2036; Expiry of patents in US/EU/China/Japan related to crystalline forms in 2037; Expiry of patents in US related to method of treatment in 2039 and 2043; Expiry of patents in US related to combination use in 2039 and EU/China in 2037; Expiry of patents in US related to formulation in 2040

Patent • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Solid Tumor • Waldenstrom Macroglobulinemia

Marginal Zone Lymphoma (ICKSH 2026) - "Bendamustine -rituximab demonstrates an ORR of ~93% and CR of ~81% in EMZL, with 5 -year PFS of ~8 0%. Lenalidomide - rituximab (R² ) offers an effective chemotherapy -free option with ORR of 93%, CR of 70%, and 5 - year OS of 96%...Zanubrutinib is now the pref erred agent based on the MAGNOLIA trial, demonstrating an ORR of 68%, CR of 26%, with favorable safety profile including low rates of atrial fibrillation (3%)...Emerging therapies include CAR -T cell therapy (axicabtagene ciloleucel showed ORR 77% in ZUMA -5), CD20×CD3 bispecific antibodies (mosunetuzumab, epcoritamab, glofitamab), non - covalent BTK inhibitors (pirtobrutinib), and antibody -drug conjugates...Key unmet needs include MZL -specific clinical trials, understanding of transformation biology, and development of novel targeted therapies. With the expanding therapeutic armamentarium, the treatment paradigm is shifting toward targeted, immune -based strategies, offering improved outcomes for..."

Atrial Fibrillation • Cardiovascular • Endocrine Disorders • Extranodal Marginal Zone Lymphoma • Hematological Malignancies • Hepatitis C • Hepatology • Immunology • Indolent Lymphoma • Infectious Disease • Lyme Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Nodal Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Sjogren's Syndrome • Splenic Marginal Zone Lymphoma • Waldenstrom Macroglobulinemia • BIRC3 • CCND1 • CD19 • CD20 • CD5 • CD79A • CREBBP • EP300 • KMT2D • MALT1 • MME • MYD88 • NOTCH2 • TNFAIP3

Combined mosunetuzumab and zanubrutinib for the treatment of patients with newly diagnosed high-burden follicular lymphoma: First results of the multicenter phase 2 mithic-FL2 trial (ASH 2025) - "Premedication with single-dose dexamethasone, diphenhydramine, andacetaminophen was mandatory before each mosun dose in C1 (and C2 if cytokine release syndrome(CRS) occurred in C1), optional thereafter. We report the first study of combined zanubrutinib and mosunetuzumab in pts withpreviously untreated high-burden FL. AEs were manageable and the safety profile was as expected forthe individual agents, with no new safety signals observed. Most patients achieved a complete metabolicresponse."

Clinical • P2 data • Acute Kidney Injury • Atrial Fibrillation • B Cell Lymphoma • Cardiovascular • Dermatology • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Lymphoma • Nephrology • Neutropenia • Non-Hodgkin’s Lymphoma • Rare Diseases • Renal Disease • CD20

The phase II study of zanubrutinib combined with R-CHOP in previously untreated diffuse large B-cell lymphoma (DLBCL) patients with specific gene-expression (ASH 2025) - "Background : Diffuse Large B cell Lymphoma (DLBCL) is the most common type of non-HodgkinLymphoma (NHL), with R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine,and prednisone) serving as the established first-line treatment regimen. The preliminary results of this phase II clinical trial have shown encouragingantitumor activity of R-CHOP combined with zanubrutinib in DLBCL patients who harbouring MCDsubtype. In addition, our findings also suggest an acceptable safety profile for the combined regimens."

Clinical • P2 data • Atrial Fibrillation • B Cell Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • CD79B • MYC • MYD88 • NOTCH1 • TP53

Cost-effectiveness of zanubrutinib versus ibrutinib in the first-line treatment for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in China. (PubMed, Health Econ Rev) - No abstract available

HEOR • Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

CA-4948-203: A Ph2 Study of Emavusertib + an Approved BTKi in Patients with CLL and Other B-cell Malignancies (clinicaltrialsregister.eu) - P1/2 | N=40 | Not yet recruiting | Sponsor: Curis Inc.

New P1/2 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Final analysis of the randomized phase 2 ROSEWOOD study of zanubrutinib + obinutuzumab vs obinutuzumab monotherapy in patients with relapsed/refractory follicular lymphoma (ASH 2025) - P2, P3 | "Introduction: While treatment advances have improved outcomes in follicular lymphoma (FL), manypatients experience multiple relapses with decreasing disease control intervals, highlighting the need fornew therapies. The final analysis of ROSEWOOD confirmed the favorable risk-benefit profile of ZO inpatients with R/R FL. The ORR and CR rate with ZO improved over time, responses remained durable, andthe PFS benefit over O was sustained. ZO had a manageable safety profile with no new safety signalsobserved."

Clinical • Monotherapy • P2 data • Atrial Fibrillation • Follicular Lymphoma • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia

COMBINATION TREATMENT WITH NOVEL BCL2 INHIBITOR SONROTOCLAX (BGB-11417) AND ZANUBRUTINIB INDUCES HIGH RATE OF COMPLETE REMISSION FOR PATIENTS WITH RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA (EHA 2025) - P1, P3 | "The phase 3 SYMPATICO study showed that combination therapy with venetoclax, a BCL2 inhibitor (BCL2i), and ibrutinib, a Bruton tyrosine kinase inhibitor (BTKi), had efficacy in patients (pts) with relapsed/refractory (R/R) MCL; however, treatment intolerance may impact its use. Sonrotoclax + zanu combination therapy was well tolerated and demonstrated encouraging antitumor activity, with a CR rate of 62.2%, and responses in pts previously treated with a BTKi. A registrational phase 3 study (NCT06742996) further assessing this combination with sonrotoclax 320mg is recruiting."

Clinical • Atrial Fibrillation • Cardiovascular • CNS Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Myelodysplastic Syndrome • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock

Phase II, single-arm, open-label, multicenter study: Efficacy of adjunctive Bruton's tyrosine kinase inhibitor (BTKi) zanubrutinib and chimeric antigen receptor (CART) in aggressive B-cell non-hodgkins lymphoma (aNHL) (ASH 2025) - "48% received bridging, 52% received CART 2nd line and 48% ≥3rd line; 78% received axi-cel and 22% liso-cel.Median length of ZLI was 7 days (range 7-10). In pts with R/R aNHL, ZLI prior to CD19 CART apheresis followed by ZM post CART resultedin 6-mo CR rates and 12-18 mo duration of CRs above historical rates reported for CART alone. Additionalstudies are needed to clarify the impact of Z exposure on changes in the TME and therapeutic effects ofCART. The safety profile of ZM was manageable with low rates of G3 toxicities."

Clinical • IO biomarker • P2 data • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Infectious Disease • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • T Cell Histiocyte Rich Large B Cell Lymphoma • CD8 • ENTPD1 • PD-1 • PD-L1

Study of Zanubrutinib, Obinutuzumab, and Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL) (clinicaltrials.gov) - P2 | N=230 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 ➔ Feb 2027 | Trial primary completion date: Feb 2026 ➔ Feb 2027

Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • TP53

The protease MALT1 is required for chronic lymphocytic leukemia genesis in Eμ-TCL1 mice (AACR 2026) - "The Bruton's Tyrosine Kinase inhibitors, such as ibrutinib, acalabrutinib, and zanubrutinib, are leading the frontline treatment in Chronic lymphocytic leukemia (CLL), but acquired resistance represents a significant clinical challenge. Our data concerning the dermatopathological complications associated with the Eμ-TCL1-/-/MALT1-/- and Eμ-TCL1wt/MALT1-/- cohorts highlights potential side effects of MALT1 inhibition and are of note due to the frequent clinical presentation of cutaneous lesions in CLL patients. Overall, our data suggest that MALT1 is required for CLL leukemogenesis and may represent a critical component in therapeutic targeting."

Preclinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Marginal Zone Lymphoma • Oncology • MALT1

From BTK in-situ mutation (C481S, A428D, etc.) to in vivo screening: A comprehensive platform to address drug resistance in BTK-targeted therapy (AACR 2026) - "Second-generation covalent BTK inhibitors, including acalabrutinib, zanubrutinib, and orelabrutinib, have also been approved for marketing in China...Moreover, in recent years, although BTK inhibitors (such as ibrutinib and acalabrutinib) have significantly improved patient survival, the issue of drug resistance has become increasingly prominent—approximately 30% of patients develop resistance due to BTK gene mutations (e.g., C481S, T474I, L528W, etc.), limiting therapeutic efficacy...These novel cell models, based on in-situ mutation technology, enable systematic evaluation of the dynamic impact of different mutations on drug binding and guide the structural optimization of next-generation inhibitors. Additionally, we have developed in vitro and in vivo screening platforms based on these mutant cell lines, enabling rapid validation of lead compounds from the molecular to the organism level, thereby accelerating BTK inhibitor development."

Preclinical • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

VIS: Front-line VenObi Combination Followed by Ven or VenZan Combination in Patients With Residual Disease: a MRD Tailored Treatment for Young Patients With High-risk CLL (clinicaltrials.gov) - P2 | N=78 | Active, not recruiting | Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto | Recruiting ➔ Active, not recruiting

Enrollment closed • Minimal residual disease • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Oncology • IGH • TP53

Systematic Review of Real-World Data on the Effectiveness and Safety Profiles of First-Line Therapies in Chronic Lymphocytic Leukemia. (PubMed, Crit Rev Oncol Hematol) - "Among 1LTT for CLL, IBR has the most extensive and consistent RWD, with results mirroring RCT outcomes. ZAN, ACA and VEN+OBI show promising results based on RWD, however, these data are less extensive but consistent with RCT outcomes. Findings highlight the value of RWD and the need for more robust data on newer agents."

Journal • Real-world evidence • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

BLOOD-dose: A Platform Trial Evaluating Dose Optimization in Hematological Diseases. (clinicaltrials.gov) - P4 | N=400 | Not yet recruiting | Sponsor: Anne Louise Tølbøll Sørensen

New P4 trial • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia