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

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

MZL-IPI Risk-adapted Targeted Therapy in Untreated MZL (clinicaltrials.gov) - P2 | N=145 | Recruiting | Sponsor: Ruijin Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Business Highlights: Orelabrutinib (InnoCare Pharma Press Release) - "Immune Thrombocytopenia ('ITP'): The pivotal Phase III study has completed patient enrollment, and a new drug application is expected to be submitted in the second quarter of 2026."

Enrollment closed • FDA filing • Thrombocytopenia

A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis (clinicaltrials.gov) - P3 | N=990 | Recruiting | Sponsor: Zenas BioPharma (USA), LLC | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Multiple Sclerosis

Treatment of BTKi+Hi-CVP Regimen for Previously Untreated MZL (clinicaltrials.gov) - P2 | N=65 | Active, not recruiting | Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

New P2 trial • Hematological Malignancies • Marginal Zone Lymphoma • Oncology • CD20

ORELABRUTINIB, A HIGHLY SELECTIVE INHIBITOR OF BRUTON'S TYROSINE KINASE(BTK), FOR THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS(SLE): RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE IIB STUDY (EULAR 2026) - No abstract available

Clinical • P2b data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Efficacy and safety analysis of BTK inhibitors combined with R-CHOP regimen in newly diagnosed double-expressor diffuse large B-cell lymphoma (PubMed, Zhonghua Xue Ye Xue Za Zhi) - "Among them, 35 patients received BTKi (zanubrutinib, orelabrutinib, acalabrutinib) combined with R-CHOP (BTKi + R-CHOP group) , and 60 received R-CHOP regimen alone (R-CHOP group) . Grade ≥ 3 adverse events primarily included neutropenia (28.6% ) and pulmonary infection (14.3% ) ; no fatal bleeding or cardiovascular events occurred. BTKi combined with R-CHOP significantly improved response rates and survival in patients with DE-DLBCL, with manageable safety."

IO biomarker • Journal • Retrospective data • B Cell Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • BCL2 • MYC

Orelabrutinib Phase 3 Monarch trial for non-active Secondary Progressive Multiple Sclerosis (naSPMS) planned (GlobeNewswire) - "Monarch, a Phase 3, global registration-directed, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of orelabrutinib in patients with naSPMS is expected to initiate in the first quarter of 2026."

Trial status • Multiple Sclerosis

Orelabrutinib in the Treatment of Relapsed/Refractory AIHA (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Peking Union Medical College Hospital

New P2 trial • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Treatment of disseminated refractory primary cutaneous marginal zone lymphoma with orelabrutinib. (PubMed, J Dtsch Dermatol Ges) - No abstract available

Journal • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Cutaneous Marginal Zone Lymphoma

Orelabrutinib Combined With Rituximab ± Lenalidomide in Response-Adapted Stratified Therapy for Untreated MZL (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: The First Affiliated Hospital with Nanjing Medical University

New P2 trial • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • CD20

MZL-IIT-O: Exploratory Study of Orelabrutinib in the Treatment of Early-stage Untreated MZL (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

New P2 trial • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology

Orelabrutinib Followed by Response-adapted Ultra-low Dose 4Gy Radiation as First-line Treatment of MALT Lymphoma (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Fudan University | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2028 ➔ Sep 2027 | Trial primary completion date: Sep 2027 ➔ Aug 2025

Enrollment closed • Trial completion date • Trial primary completion date • B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology

PD-1 Inhibitor Combined With Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO) for Newly Diagnosed PCNSL and SCNSL. (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: The First Affiliated Hospital with Nanjing Medical University

New P2 trial • B Cell Lymphoma • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma

ORBIT: Phase II Study of Orelabrutinib in Combination With Romiplostim N01 in Patients With Primary Immune Thrombocytopenia (ITP) Who Have Received At Least One Prior Line of Therapy (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: Peking Union Medical College Hospital

New P2 trial • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura • IL4 • IL9

Zenas also expects to initiate a global Phase 3 trial of orelabrutinib in patients with non-active Secondary Progressive Multiple Sclerosis (naSPMS) in this quarter. (GlobeNewswire)

New P3 trial • Multiple Sclerosis

Marginal zone lymphoma presenting with chylous ascites: A rare clinical manifestation and successful treatment with orelabrutinib-rituximab. (PubMed, SAGE Open Med Case Rep) - "Clinicians should consider lymphoma in the differential diagnosis of unexplained chylous ascites. Prompt etiologic treatment can result in favorable outcomes even in elderly patients with advanced disease."

Journal • B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Splenic Marginal Zone Lymphoma

Efficacy of BTK inhibitor combined with rituximab and lenalidomide in newly diagnosed diffuse large B-cell lymphoma: a single-center, retrospective study. (PubMed, Ann Hematol) - "The Smart Start trial demonstrated the combination of ibrutinib, rituximab, and lenalidomide resulted in impressive efficacy in newly diagnosed non-GCB diffuse large B-cell lymphoma (DLBCL)...The OR2 regimen (orelabrutinib, rituximab and lenalidomide) was administered to 60.7% (51/84) patients, and ZR2 regimen (zanubrutinib, rituximab and lenalidomide) to 39.3% (33/84) patients...Fifty-one (60.7%) patients reported grade ≥ 3 adverse events, with the most common being neutropenia (54.8%). This real-world data support SMART regimen as a potential treatment option for DLBCL patients, with promising efficacy and acceptable safety."

Journal • Retrospective data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

Rituximab, Lenalidomide, and Orelabrutinib Combination Regimen in the Treatment of marginal zone cell lymphoma: a Prospective, Single-Arm, Phase II Clinical Study (ChiCTR) - P2 | N=46 | Not yet recruiting | Sponsor: The First Affiliated Hospital, College of Medicine, Zhejiang University; The First Affiliated Hospital, College of Medicine, Zhejiang University

New P2 trial • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • CD20

Rituximab, high-dose methotrexate plus orelabrutinib as induction therapy in newly diagnosed primary central nervous system lymphoma. (PubMed, Leukemia) - No abstract available

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

Application of Orelabrutinib With or Without CD20 Monoclonal Antibody in Previously Untreated Marginal Zone Lymphoma (clinicaltrials.gov) - P4 | N=88 | Recruiting | Sponsor: Beijing Tongren Hospital

New P4 trial • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology

A Study of Rocbrutinib Versus Investigator's Choice of BTK Inhibitors in Patients With Relapsed or Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P3 | N=394 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.

Monotherapy • New P3 trial • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

Orelabrutinib has been approved as a first-line treatment for CLL/SLL and included in the national medical insurance program, and is listed as a Level I recommendation in the Chinese Society of Clinical Oncology (CSCO) Lymphoma Diagnosis and Treatment Guidelines (2025 Edition). (InnoCare Pharma Press Release)

Clinical guideline • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

A prospective observational study of Orelabrutinib combined with anti-CD20 monoclonal antibody followed by Orelabrutinib maintenance as first-line treatment for MZ (ChiCTR) - P=N/A | N=40 | Not yet recruiting | Sponsor: The Affiliated Hospital of Southwest Medical University; The Affiliated Hospital of Southwest Medical University

New trial • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • CD20

Bendamustine combined with Zuberitamab (BZ) followed by Orelabrutinib combined with Zuberitamab (OZ) in the treatment of newly diagnosed marginal zone lymphoma:A Phase II prospective clinical study (ChiCTR) - P=N/A | N=74 | Not yet recruiting | Sponsor: The First Affiliated Hospital of the Air Force Medical University; The First Affiliated Hospital of the Air Force Medical University

New trial • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • CD20