Inokai (orelabrutinib) / InnoCare, Zenas BioPharma - LARVOL DELTA

A predictive model for treatment failure in CLL/SLL patients receiving BTK inhibitor: A multi-center retrospective study (ASH 2025) - " We conducted a retrospective analysis of CLL/SLL patients treated with ibrutinib or second-generation BTK inhibitors (orelabrutinib and zanubrutinib) across three centers in China. This multi-center study developed a validated predictive model for BTK inhibitor treatment failure in CLL/SLL, integrating genetic and metabolic factors. The model aids in early identification of high-risk patients, facilitating individualized treatment decisions and optimal resource allocation."

Predictive model • Retrospective data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma

Efficacy and safety of orelabrutinib monotherapy in patients with chronic lymphocytic leukemia: A retrospective real-world study (ASH 2025) - "Five pts had a history of BTKi treatment (ibrutinib, n=3; Zanubrutinib, n=2), all of whom switched due to inadequate efficacy or AEs. This real-world study suggested that orelabrutinib monotherapy showed promising efficacy and a favorable safety profile in pts with CLL, both as first-line and subsequent therapy. Further prospective investigations are needed to validate the observations."

IO biomarker • Monotherapy • Real-world • Real-world evidence • Retrospective data • Chronic Lymphocytic Leukemia • Diabetes • Dyslipidemia • Heart Failure • Hematological Malignancies • Hypertension • Leukemia • Metabolic Disorders • Thrombocytopenia • IGH • TP53

A Phase II study of time-limited treatment with orelabrutinib plus bendamustine and obinutuzumab (OBG) in patients with treatment-Naïve CLL/SLL patients (ASH 2025) - "Background: FCR (fludarabine, cyclophosphamide, and rituximab) has been demonstrated to improve outcomes in previously untreated Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) CLL patients, but only for suitable patients, which limits it clinical application.Lower toxicity strategies, such as Bendamustine-Obinutuzumab or Bendamustine-Rituximab, demonstrated better tolerability but did not achieve comparable efficacy.BTK inhibitors (BTKi) are recommended for long-term therapy in CLL/SLL and time-limited treatment regimen has been hot topics. The Time-Limited Treatment of OBG regimen shows efficacy in unfit CLL/SLL patients, which achieved high rates of complete response combined with undetectable minimal residual disease. Safety analysis indicates that the OBG regimen is well-tolerated and adverse events are manageable. These findings support further investigation of the OBG regimen to optimize treatment outcomes in this patient population."

Clinical • P2 data • Atrial Fibrillation • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Herpes Zoster • Hypertension • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • Thrombocytopenia • Varicella Zoster • IGH • TP53

Data update of a single-arm, Phase II Study of orelabrutinib with/without Rituximab in patients with chronic lymphocytic leukemia/small Lymphocytic Lymphoma after BTK inhibitor therapy (ASH 2025) - "All patients achieved remission, and MRD significantly decreased after 9 months, and uMRD began to emerge. Given these promising findings, this therapeutic strategy holds the potential to serve as a novel treatment option for patients with CLL/SLL."

Clinical • P2 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • IGH • TP53

Efficacy and safety of bmetl regimen (Orelabrutinib plus Semustine, Temozolomide and Lenalidomide) with subsequent maintenance treatment in elderly/frail patients with CNSL (ASH 2025) - "After induction therapy, patients with objective response received sequential MT regimen (methotrexate 3 mg/m 2 , day 1; thiotepa 20 mg/m 2 , day 2) in a 21-day cycle for 2-4 cycles... BMeTL regimen with subsequent maintenance treatment is effective and well-tolerated for elderly/frail patients with CNSL. This study provides a potential novel strategy for this elderly/frail population."

Clinical • Agranulocytosis • CNS Lymphoma • Geriatric Disorders • Granulocytopenia • Hematological Malignancies • Infectious Disease • Lymphoma • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma • Thrombocytopenia

Upfront maintenance therapy improves the prognosis of patients with diffuse large B-cell lymphoma in the era of novel agents: A multicenter retrospective study (ASH 2025) - "Patients received rituximab, lenalidomide, or BTKi for up to two years as maintenance therapy after 6-8 cycles of R-CHOP±X (X mainly indicated BTKi or lenalidomide) treatment...There is no statistical difference between the two types of covalent BTKi (zanubrutinib or orelabrutinib )...Future prospective studies in larger cohorts are warranted to evaluate a broader range of maintenance strategies. Keywords diffuse large B-cell lymphoma, maintenance therapy, survival"

Retrospective data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma

A retrospective study on orelabrutinib combined with anti-CD20 monoclonal antibody regimen in treating mucosa-associated lymphoid tissue lymphoma. (ASH 2025) - "Despite the limited sample size in this retrospective study, the results indicate that the Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen demonstrates favorable safety and efficacy in MALT lymphoma patients, providing an effective and safe treatment option for this population."

Retrospective data • Extranodal Marginal Zone Lymphoma • Leukopenia • Lymphoma • Marginal Zone Lymphoma • Thrombocytopenia

Efficacy, safety, and NGS analysis of orelabrutinib combined with obinutuzumab in untreated marginal zone lymphoma (ASH 2025) - "NGS of tumor tissue is instrumental for elucidating the molecular pathogenesis of MZL and for guiding individualized therapeutic strategies. Future updates will incorporate additional follow-up data."

Clinical • Next-generation sequencing • Epstein-Barr Virus Infections • Hematological Malignancies • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Thrombocytopenia • KMT2C • NOTCH2 • TCF3

Orelabrutinib plus rituximab-based chemoimmunotherapy regimens in relapsed or refractory marginal zone lymphoma: A multicentric phase II trial (ASH 2025) - "Eligible patients who failed to achieve partial response (PR) after 4 cycles of 1L CIT or relapsed < 2 years were switched to O plus bendamustine and rituximab (BR). Those who achieved PR after 4 cycles or relapsed ≥ 2 years after 1L therapy received O added to the previous regimen (rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone or with cyclophosphamide, vincristine, and prednisone [R-CHOP/R-CVP]) for continued treatment... Our preliminary data demonstrate that orelabrutinib in combination with rituximab-based chemoimmunotherapy is effective and well-tolerated in R/R MZL. These findings warrant further prospective studies to validate, and longer follow-up is needed to confirm PFS and OS outcomes."

Clinical • P2 data • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma

The efficacy and safety of orelabrutinib-based regimens in the treatment of marginal zone lymphoma: A retrospective real-world study (ASH 2025) - "38 MZL patients were enrolled in the study. Among them, 17 patients (44.7%) received orelabrutinib-based regimens, with the median treatment duration of 4 months (range, 1 - 13 months). The median age was 66 years (range, 52 - 81 years), with 9 males (52.9%)."

Real-world • Real-world evidence • Retrospective data • B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Nodal Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Splenic Marginal Zone Lymphoma

Orelabrutinib for elderly patients with stage IV marginal zone lymphoma involving the central nervous system: A case report and clinical implications (ASH 2025) - "The patient was ultimately diagnosed with mild generalized myasthenia gravis and initiated on oral tacrolimus therapy; however, no significant improvement in bilateral eyelid ptosis was observed. This case describes a rare instance of MZL with multiple extranodal involvement and CNS invasion. Its diagnostic process, therapeutic course, and outcomes carry significant reference value for the clinical management of MZL with CNS involvement. Regarding treatment, the R-miniCHOP regimen partially controlled systemic lesions, while intrathecal injections were administered to specifically clear CNS lesions."

Case report • Clinical • Metastases • CNS Disorders • Hematological Malignancies • Ischemic stroke • Lymphoma • Marginal Zone Lymphoma • Myasthenia Gravis • Myelofibrosis • Non-Hodgkin’s Lymphoma

Successful treatment of two refractory acute lymphoblastic leukemia cases with an orelabrutinib-based regimen (ASH 2025) - "Treatment with the CD22 monoclonal antibody (Inotuzumab ozogamicin) reached a CRi (complete remission with incomplete hematologic recovery), but relapse occurred one month later...Subsequently, blinatumomab was administered to eradicate MRD, followed by a matched sibling allogeneic hematopoietic stem cell transplant...Due to financial constraints, she was unable to receive immunotherapy and was instead treated with orelabrutinib combined with venetoclax and chidamide...Conclusion The successful treatment of these two cases demonstrates the potential of orelabrutinib in refractory or primary resistant B-ALL patients, offering a novel therapeutic option for this high-risk population. This study supports further exploration of orelabrutinib-containing regimens in the clinical management of B-ALL."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • CD22 • IKZF1 • PBX1 • SETD2

Therapeutic drug monitoring-guided individualized dosing of multiple BTK inhibitors combined with voriconazole: Real-world evidence on managing drug-drug interactions (ASH 2025) - "The regimens included ibrutinib [560 mg once a day (QD), reduced to 140 mg QD], zanubrutinib (160 mg BID, reduced to 80 mg QD), orelabrutinib (150 mg QD, reduced to 50 mg QD), and acalabrutinib (100 mg BID, reduced to 100 mg QD). The study suggests that coadministration of BTKis with CYP3A inhibitors can significantly affect its pharmacokinetic properties, and TDM has been shown to optimize the individualized dose adjustments of BTKis in the presence of DDIs. We are currently conducting a prospective real-world study to further elucidate exposure-response relationships, aiming to transition BTKi therapy from empirical to precision medicine. These efforts will provide valuable insights for optimizing dosing regimens, guiding personalized treatment decisions, and improving clinical outcomes."

Clinical • HEOR • Real-world • Real-world evidence • Hematological Malignancies • Infectious Disease • Respiratory Diseases

Orelabrutinib in the treatment of pure red cell aplasia after allogeneic hematopoietic stem cell transplantation (ASH 2025) - "Reported therapeutic strategies for post-transplant PRCA include Rituximab, Bortezomib, Cyclosporine A, Glucocorticoid, Cyclophosphamide, Daratumumab, and erythropoietin. Orelabrutinib has demonstrated both safety and efficacy in eliminating autoantibodies targeting erythroid precursor cells. Thus, it represents a viable therapeutic option for refractory post-transplant PRCA following ABO-incompatible allo-HSCT."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Transplantation

Efficacy and safety of orelabrutinib, obinutuzumab, and lenalidomide in previously untreated marginal zone lymphoma: Preliminary results from a prospective, single-arm, multicenter, Phase II study (ASH 2025) - P2 | "This phase II study demonstrates that the novel triple-combination regimen shows promisingefficacy in treatment-naïve MZL patients, with an impressive overall response rate (88.9%) and completeresponse rate (72.2%), particularly in SMZL patients who achieved 100% CR. The regimen exhibited amanageable safety profile with no grade 4-5 adverse events. Early MRD negativity in SMZL suggestspotential for durable remissions."

Clinical • P2 data • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Hematological Malignancies • Herpes Zoster • Indolent Lymphoma • Infectious Disease • Influenza • Leukopenia • Lymphoma • Marginal Zone Lymphoma • Monoclonal Gammopathy • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases • Splenic Marginal Zone Lymphoma • Thrombocytopenia • Varicella Zoster

Preliminary analysis of orelabrutinib combined with obinutuzumab in the treatment of marginal zone lymphoma (Orion Study) (ASH 2025) - P2 | "The OG regimen demonstrated promising antitumor activity in treatment-naïve MZL with no severetoxicities observed. These early results support OG as a potential chemotherapy-free first-line option forMZL. Longer follow-up is needed to assess durability of response and survival outcomes."

Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma

Real-world study on the impact of continuous treatment dose interruption or reduction of COVALENT BTK inhibitors on efficacy: A 7-year follow-up in chronic lymphocytic leukemia specialized clinics at tertiary hospitals in shanghai, China (ASH 2025) - "Eligible patients had undergone at least one month of covalent BTKitherapy, including ibrutinib, zanubrutinib, or orelabrutinib. A total of 324 patients under specialized outpatient observation were enrolled; among BTKi-treated patients, the median age was 65 years (range, 25–91), with a male-to-female ratio of 2.6:1.Treatment-naïve (TN) patients numbered 225 (69.44%), and relapsed/refractory (R/R) patients numbered99 (30.56%). The proportion of TN patients receiving BTKi increased from 22.7% in 2018 to 100% in 2024.Patients younger than 65 years accounted for 40.74% (132/324), and 43.5% (87/200) exhibiteddel(17p)/TP53 aberrations, reflecting the evolution of BTKi-based regimens in clinical practice inChina.With a median follow-up of 42 months, the median OS was not reached, and the 42-month PFSrate was 70.22%. Among all patients, 88 received full-dose BTKi, 231 were in the dosereduction/interruption group, and 5 were lost to follow-up.A total of 352 dose reduction..."

Clinical • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Infectious Disease • Novel Coronavirus Disease • TP53

Mesutoclax (ICP-248) monotherapy or combined with orelabrutinib demonstrates encouraging activity and safety in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (ASH 2025) - P1, P2/3 | "Mesutoclax monotherapy or in combination with orelabrutinib demonstrated a tolerablesafety profile across all dose levels tested. Substantial efficacy and deep remission were observed in bothTN CLL/SLL patients receiving mesutoclax 125mg combined with orelabrutinib and R/R CLL/SLL treatedwith mesutoclax alone."

Clinical • Monotherapy • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • TP53

Polatuzumab vedotin combined with orelabrutinib and rituximab (PRO Regimen) as frontline therapy in elderly and frail patients with diffuse large B-cell lymphoma (DLBCL): Results from A phase II study (ASH 2025) - "Title: Polatuzumab Vedotin Combined with Orelabrutinib and Rituximab (PRO Regimen) as FrontlineTherapy in Elderly and Frail Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Results from a Phase IIStudyBackground :Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in theelderly population, with treatment often complicated by frailty, comorbidities, and poor tolerance tostandard R-miniCHOP regimens. This Phase II trial highlights the potential of Polatuzumab Vedotin, Orelabrutinib, and Rituximab (PROregimen) as a well-tolerated, chemotherapy-free frontline treatment for elderly and frail patients withDLBCL. Achieving an impressive CR rate of 66.7% and an ORR of 94.5%, coupled with a favorable safetyprofile, the PRO regimen addresses a critical unmet need in this vulnerable population. Furtherinvestigations with larger cohorts are warranted to confirm these promising results and to evaluate long-term outcomes, including..."

Clinical • P2 data • Atherosclerosis • Atrial Fibrillation • B Cell Lymphoma • Cardiovascular • Coronary Artery Disease • Diabetes • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Hypertension • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Respiratory Diseases • Thrombocytopenia

Efficacy and safety of rituximab, high-dose methotrexate, and thiotepa (R-MT) as first-line induction therapy for primary central nervous system diffuse large B-cell lymphoma (ASH 2025) - "The IELSG 32 study confirmed that a thiotepa-containing multi-drugcombination regimen (rituximab + high-dose methotrexate + cytarabine + thiotepa, MATrix) achieves anoverall objective response rate (ORR) of 87% when used as induction therapy for PCNSL...At a median follow-up of 19 months, the 2-year PFS rateand OS rate were 63.9% and 82.9%, respectively.Based on subsequent treatment strategies, patients were divided into three groups: 15 patients receivedinduction therapy alone, 16 patients received sequential maintenance therapy (including Bruton tyrosinekinase inhibitors [BTKi: 7 with zanubrutinib, 4 with orelabrutinib] or immunomodulatory drugs [IMiD: 5with lenalidomide, 1 with pomalidomide]), and 5 patients received ASCT as consolidation therapy.Subgroup analysis showed that the proportion of patients aged > 60 years in the sequential maintenancetherapy group was 81.3%, which was significantly higher than that in the other two groups (81.3% vs.53.3% vs. 0%,..."

Clinical • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Infectious Disease • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Respiratory Diseases

Chemotherapy-free induction with pomalidomide, orelabrutinib, and rituximab (POR) followed by high-dose methotrexate,rituximab and orelabrutinin (ROM) in newly diagnosed primary CNS lymphoma: Interim analysis of a phase II study (ASH 2025) - P2 | "The data cut-off date was 15th July 2025, 33 patients were enrolled in this study. The median age was 59years (range, 22-79 years). 11 patients had eye involvement and 2 patient had leptomeningesinvolvement."

P2 data • Bone Marrow Transplantation • CNS Lymphoma • Dermatology • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Thrombocytopenia

Orelabrutinib plus anti-PD-1 antibody and fotemustine for newly diagnosed primary central nervous system lymphoma: Phase I/II results (ASH 2025) - P1/2 | "Orelabrutinib plus anti–PD-1 antibody and fotemustine demonstrated promising activity andacceptable safety in newly diagnosed PCNSL, with a high objective response rate. These findings supportthe potential of orelabrutinib-based chemoimmunotherapy as a promising frontline strategy. The studyis still ongoing and final results will be presented in the future."

P1/2 data • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Infectious Disease • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Respiratory Diseases • Thrombocytopenia

Orelabrutinib, sintilimab, and temozolomide (OST) in relapsed/refractory primary central nervous system lymphoma (ASH 2025) - P2 | "Clinically meaningful survival benefit was observed (median PFS 9.0 months; 2-year OS 53.1%).Disease status was a key determinant of efficacy, with relapsed patients significantly outperformingthose with refractory disease. The chemo-free regimen was generally well tolerated, supporting itsfurther evaluation in prospective studies."

IO biomarker • Atrial Fibrillation • B Cell Lymphoma • CNS Lymphoma • Hematological Malignancies • Infectious Disease • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Primary Central Nervous System Lymphoma • Respiratory Diseases • BCL2 • PD-1

Orelabrutinib combined with R-CDOP regimen for first-line treatment of diffuse large B-cell lymphoma with high-risk CNS-IPI (ASH 2025) - P2 | "Patients received orelabrutinib combined with an R-CDOP regimen:orelabrutinib 150 mg orally once daily; rituximab 375 mg/m²; cyclophosphamide 750 mg/m²; liposomaldoxorubicin 30 mg/m²; vinorelbine 25 mg/m² on day 1; and prednisone 100 mg daily on days 1–5.Treatment was given in 21-day cycles for a total of six cycles. Median OSwas 38.1 months, 1- and 2-year OS rates were 93.8 % and 90.2 %, respectively.During the study, all patients experienced grade 1-2 adverse reactions, with grade 3-4 adverse reactionsoccurring in 67.6% (25/37). The most common grade 3-4 adverse events were neutropenia (59.5%),anemia (24.3%) and thrombocytopenia (16.2%).ConclusionIn treatment-naïve, high-risk CNS-IPI DLBCL, the orelabrutinib plus R-CDOP regimen achieves early, deep,and durable responses with low CNS relapse rates (0% at 1 year and 9.3% at 2 years), which aresignificantly lower than the relapse rates with MTX plus R-CHOP prophylaxis (12.4% at 2 years), and..."

Clinical • IO biomarker • B Cell Lymphoma • Cardiovascular • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia • BCL2

Exploration of optimal high-dose methotrexate-based therapy for patients with primary CNS lymphoma: A real-world study in China (ASH 2025) - "Amongthem,19 patients were treated with rituximab (R) plus HD-MTX (HD-MTX±R); 8 patients were administeredR, HD-MTX, and cytarabine (R-MA); 50 patients received R, lenalidomide, and HD-MTX (R2-MTX); and 33patients received pomalidomide plus orelabrutinib and R followed by sequential HD-MTX (POR/ROM).The mean age of all patients was 56.9 years; 52.7% of the patients were male, and the majority had anIELSG score of ≥2 (2-3, 56.4%; 4-5, 24.6%)... HD-MTX-based treatments demonstrated encouraging efficacy, particularly among patientswho received POR/ROM or R2-MTX. These findings support adding small molecular target drugs to HD-MTX as a viable first-line treatment option for patients with PCNSL. Prospective studies are warranted toconfirm these results."

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