Feasibility of Treating Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma With Zanubrutinib in Combination With the BCL2 Inhibitor, Sonrotoclax, Focusing on Access for Underrepresented Ethnic/Racial Minorities

This phase I trial tests zanubrutinib in combination with sonrotoclax for treating underrepresented ethnic and racial minorities with B-cell non-Hodgkin lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Many racial and ethnic minorities face additional treatment challenges which may lead to poorer outcomes, however, there are fewer racial and ethnic minorities participating in clinical trials. Zanubrutinib, a type of tyrosine kinase inhibitor, blocks a protein called Bruton tyrosine kinase (BTK), which may help keep cancer cells from growing. Sonrotoclax works by blocking a protein called B-cell lymphoma-2 (Bcl-2). This protein helps certain types of blood cancer cells to survive and grow. When sonrotoclax blocks Bcl-2, it slows down or stops the growth of cancer cells and causes them to die. Zanubrutinib and sonrotoclax have been shown to be an effective treatment for B-cell cancers. Giving zanubrutinib in combination with sonrotoclax may be effective in treating ethnic and racial minorities with relapsed or refractory B-cell non-Hodgkin lymphoma.

开始日期2026-02-07

申办/合作机构

City of Hope National Medical Center

[+1]

NCT06735664

/ Not yet recruiting临床1期IIT

A Phase I Study of Covalent BTK Inhibitor Zanubrutinib in Combination With a CD3-CD20 Bispecific Antibody Odronextamab in Patients With Richter's Transformation

This phase I trial tests the safety and side effects of zanubrutinib in combination with odronextamab and how well it works in treating patients with Richter's transformation. Zanubrutinib, a tyrosine kinase inhibitor, blocks a protein called Bruton tyrosine kinase (BTK), which may help keep cancer cells from growing. Odronextamab is a bispecific monoclonal antibody that can bind to two different antigens at the same time. Odronextamab binds to CD20 found on B-cells (a type of white blood cell) and on many B-cell cancers and to CD3 on T-cells (also a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Giving zanubrutinib in combination with odronextamab may be safe, tolerable and/or effective in treating patients with Richter's transformation.

开始日期2025-08-14

申办/合作机构

City of Hope National Medical Center

[+1]

NCT06854003

/ Not yet recruiting临床2期IIT

A Randomized Phase 2 Study of Bendamustine, Rituximab, Cytarabine (AraC) Induction With Zanubrutinib (BRAZAN) Followed by Zanubrutinib/Rituximab +/- Sonrotoclax Maintenance in Treatment-Naïve Mantle Cell Lymphoma

This study aims to evaluate the efficacy and safety of an induction regimen combining Bendamustine, Rituximab, Cytarabine (AraC), and Zanubrutinib (BRAZAN), followed by maintenance therapy with Zanubrutinib and Rituximab with or without Sonrotoclax in participants with Mantle Cell Lymphoma (MCL).
The names of the study drugs involved in this study are:
* bendamustine (a type of alkylating agent)
* rituximab (a type of monoclonal antibody)
* cytarabine (a type of antineoplastic)
* zanubrutinib (a type of kinase inhibitor)
* sonrotoclax (a type of BCL2 inhibitor)

开始日期2025-08-01

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+1]

100 项与泽布替尼相关的临床结果

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100 项与泽布替尼相关的转化医学

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100 项与泽布替尼相关的专利（医药）

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620

项与泽布替尼相关的文献（医药）

2025-12-01·Blood Research

Relative efficacy of systemic treatments for patients with relapsed/refractory chronic lymphocytic leukemia: a network meta-analysis according to 17p deletion/TP53 mutations

Article

作者: Lim, Joo Han ; Kim, Jinchul ; Lee, Moon Hee ; Cho, Jinhyun

Abstract:

Purpose:

This network meta-analysis aimed to evaluate the relative efficacy of systemic treatments in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL), focusing on key genetic mutations, specifically the 17p deletion and TP53 mutations.

Methods:

We conducted a systematic literature review to identify all publicly available randomized controlled trials (RCTs) using PubMed, EMBASE, the Cochrane database, and meeting abstracts published through December 2023. A Bayesian network meta-analysis was performed to estimate the hazard ratios (HRs) for progression-free survival (PFS) with 95% confidence intervals (CIs) and to determine the ranking of the included regimens.

Results:

Twelve trials involving 4,437 patients and 13 treatment options were included in the meta-analysis. Venetoclax plus rituximab and zanubrutinib emerged as the most effective treatments for the overall R/R CLL population, showing the lowest PFS HR (HR 0.62, 95% CI 0.32–1.20 and HR 0.65, 95% CI 0.49–0.86, respectively) versus ibrutinib, and were ranked as the best agent (surface under the cumulative ranking curve [SUCRA] value of both 90%, respectively) among the included drugs. In the 17p deletion/TP53 mutation subgroup, zanubrutinib demonstrated the most favorable efficacy (HR 0.52, 95% CI 0.31–0.88 versus ibrutinib) with the highest SUCRA value (97%). In patients without these mutations, venetoclax plus rituximab was the most effective (HR 0.49, 95% CI 0.26–0.94 versus ibrutinib) with a SUCRA value of 94%.

Conclusion:

Our findings highlight the superior efficacy of venetoclax plus rituximab and zanubrutinib for treating R/R CLL and confirm that the role of each regimen may vary depending on the clinically significant mutations.

2025-06-01·ANTI-CANCER DRUGS

BTK inhibitors enhance NKG2D ligand expression by regulating IL-10/STAT3 pathway in activated non-GCB diffuse large B-cell lymphoma cells

Article

作者: Jia, Zhu-xia ; Xiao, Bi-tao ; Qin, Wei ; Li, Jin ; Cai, Xiao-hui ; Zhou, Min ; Lu, Xu-zhang

The aim of this study is to explore the role of the IL-10/STAT3 pathway in the upregulation of natural killer group 2, member D (NKG2D) ligands (MICA and ULBP2) induced by Bruton’s tyrosine kinase (BTK) inhibitors in non-germinal center B-cell-like diffuse large B-cell lymphoma cells. The expression levels of NKG2D ligands and the IL-10/STAT3 pathway in SUDHL4, U2932, and OCI-LY3 cells were analyzed using western blotting. After stimulation of the B-cell receptor signaling pathway with IgM antibodies, the expression levels of NKG2D ligands, as well as IL-10 and phosphorylated STAT3 (p-STAT3) were significantly reduced. In contrast, treatment with ibrutinib produced effects opposite to those induced by IgM antibodies. Additionally, treatment of U2932 and OCI-LY3 cells with the STAT3 inhibitor (STAT3-IN-1) led to an increase in NKG2D ligand expression and a decrease in IL-10 levels. When IL-10 neutralizing antibodies were introduced, p-STAT3 levels decreased, and NKG2D ligand expression increased. Similar outcomes were observed when the BTK inhibitors ACP-196 and BGB-3111 were administered. Our findings suggest that the IL-10/STAT3 pathway plays a key role in the upregulation of NKG2D ligands induced by BTK inhibitors in U2932 and OCI-LY3 cells.

2025-06-01·AMERICAN JOURNAL OF HEMATOLOGY

Waldenström Macroglobulinemia: 2025 Update on Diagnosis, Risk Stratification, and Management

Review

作者: Gertz, Morie A.

ABSTRACT:

Disease Overview:

Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity.

Diagnosis:

The presence of IgM monoclonal protein associated with ≥ 10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in most IgM MGUS patients. MYD88 is not required for the diagnosis.

Risk Stratification:

Age, albumin, hemoglobin level, platelet count, β2 microglobulin, Lactate dehydrogenase (LDH), and monoclonal IgM concentrations are characteristics that are predictive of outcomes.

Risk‐Adapted Therapy:

Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab‐monotherapy is inferior to combination regimens. Recommended first‐line therapy can be chemoimmunotherapy or a covalent Bruton tyrosine kinase inhibitor. The preferred Mayo Clinic induction is either rituximab and bendamustine (without rituximab maintenance) or zanubrutinib.

Management of Refractory Disease:

Bortezomib, cyclophosphamide, fludarabine, thalidomide, everolimus, pirtobrutinib, carfilzomib, lenalidomide, bendamustine, and venetoclax have all been shown to have activity in relapsed WM. Given WM's natural history, the reduction of therapy toxicity is an important part of treatment selection. Most patients succumb to causes unrelated to macroglobulinemia.

1,493

项与泽布替尼相关的新闻（医药）

2025-05-28

·靶点圈

一文带你了解BTK抑制剂的十年变革：从血液肿瘤到自身免疫病的跨界征途

01BTK的分子结构与作用机制BTK的分子结构BTK是一种由659个氨基酸组成的非受体酪氨酸激酶，分子量约76kDa，属于Tec激酶家族。其结构包含5个主要功能域，从N端到C端依次为：● PH结构域：结合磷脂酰肌醇三磷酸(PIP3)，介导细胞膜定位；● SH3结构域：结合富含脯氨酸的蛋白(如BCAP)，参与信号复合物组装，是BCR信号激活的前提；● SH2结构域：识别磷酸化酪氨酸残基，与活化的CD79a/b等分子结合，传递BCR信号；● SH1/TK结构域：包含关键的催化位点(Cys481、Tyr551)和ATP结合口袋；● C端尾部：含核定位信号(NLS)和核输出信号(NES)，调控BTK在胞质与细胞核间的穿梭，影响其功能多样性。这些结构域通过协同作用，实现BTK的膜定位、信号传导和底物磷酸化功能。图1 BTK的化学结构BTK的信号通路调控BTK通过BCR、TLR、CXCR4等受体激活，从而磷酸化下游分子(如PLC-γ)激活NF-κB和MAPK通路，参与免疫应答和炎症反应。图2 BTK在BCR、TLR、趋化因子受体和FcR信号转导通路中的作用BTK与其他激酶的协同作用与Lyn、Syk、PI3K等激酶形成信号网络。Lyn磷酸化CD79A/B的ITAM招募Syk，Syk激活BTK，共同维持BCR通路活化。PI3K通过生成PIP3激活Akt/mTOR通路，与BTK协同促进细胞生存代谢。图3 刺激B细胞中BTK活化的细胞表面受体02BTK的表达调控与生物学功能BTK的广泛表达BTK不仅表达于B细胞，还存在于髓系细胞(如单核细胞/巨噬细胞、树突状细胞、肥大细胞、中性粒细胞)中，参与多种免疫细胞的信号传导。BTK的功能及作用机制● 调控B细胞活化与自身抗体产生：1)B细胞发育与激活：BTK是B细胞受体(BCR)信号通路的关键激酶，调控B细胞的发育、活化与分化，促进B细胞增殖与抗体分泌。其异常激活与B细胞恶性肿瘤(如慢性淋巴细胞白血病CLL、套细胞淋巴瘤MCL)、自身免疫病密切相关。2)B细胞代谢调控：BTK抑制B细胞线粒体呼吸，影响其活化状态。在多发性硬化(MS)中，BTK通过调节B细胞代谢，增强其刺激T细胞分泌促炎因子(如IFN-γ、TNF-α)的能力。3)B细胞与T细胞的协同作用：BTK抑制B细胞表面共刺激分子(如CD80/CD86)的表达，减少其对T细胞的激活，抑制Th1/Th17型免疫反应。反之，BTK过度激活会增强B-T细胞相互作用，加剧自身免疫炎症。图4 NLC、LAM和恶性B细胞之间的相互作用和信号转导● 调控固有免疫细胞的炎症放大作用：1)巨噬细胞与树突状细胞(DCs)：BTK通过Toll样受体(TLR)信号通路激活巨噬细胞和DCs，促进M1型促炎表型，增加促炎因子(如IL-23、TNF-α)和趋化因子(如CXCL13)的分泌，参与银屑病、RA等炎症性疾病的发病。2)肥大细胞与嗜碱性粒细胞：在慢性自发性荨麻疹(CSU)中，BTK介导IgE-FcεRI信号，促进肥大细胞释放组胺和炎症介质，引发过敏反应和气道高反应性。3)中性粒细胞与破骨细胞：BTK调控中性粒细胞的氧化应激反应(如超氧化物生成)，参与银屑病皮损炎症；同时促进破骨细胞分化，加剧类风湿关节炎(RA)患者的骨侵蚀。图5 BTK在骨髓细胞中的作用BTK的结构异常与疾病关联● XLA(X连锁无丙种球蛋白血症)：BTK基因缺失或突变(如C481突变)导致B细胞发育停滞，表现为抗体缺乏和反复感染。● 自身免疫病：BTK过度激活或构象改变(如C端尾部磷酸化异常)可增强B细胞和固有免疫细胞的活化，促进自身抗体产生和炎症反应(如SLE、RA)。03BTK抑制剂的分类与耐药机制BTK抑制剂(BTKIs)的分类图6 BTK抑制剂的作用机制● 共价不可逆抑制剂：不可逆结合BTK的C481位点(如伊布替尼、阿卡替尼、泽布替尼)，阻断BCR信号，用于B细胞恶性肿瘤，显著改善患者生存。但长期使用易诱导C481S突变，导致耐药。● 共价可逆抑制剂：可逆结合C481位点(如瑞扎布替尼)，减少脱靶效应。但仍可能因C481S或L528W突变耐药。● 非共价可逆抑制剂：不结合C481，通过阻断ATP结合或降低激活标记物(如芬布替尼)，适用于C481突变(如C481S)的耐药患者。但可能因T474I、L528W等新突变导致耐药。表1 BTK抑制剂分类由BTK基因突变引发的耐药● 激酶功能型突变：1)C481位点突变：如C481S/R/F/Y，占共价抑制剂耐药的60–90%。突变导致BTK与共价抑制剂(如伊布替尼)的共价结合失效，但保留激酶活性，维持BCR信号传导。2)T474I突变：位于激酶结构域，增强BTK自身磷酸化(Y223位点)，激活下游PLCγ2/NF-κB通路，常见于阿卡替尼治疗后。● 激酶失活型突变：1)L528W突变：导致BTK激酶活性丧失，但通过“支架功能”与HCK、ILK等激酶结合，维持下游信号传导，常见于泽布替尼治疗后的CLL。2)其他位点突变：如V416L、A428D、M437R等，通过改变BTK构象或与抑制剂结合口袋，导致非共价抑制剂(如吡托布鲁替尼)耐药。● 下游信号通路激活：1)PLCγ2突变：如S707F、R665W、E1139del，激活下游NF-κB通路，绕过BTK信号维持B细胞存活，常见于WM、CLL。图7 BTK和PLCγ2突变由其他因素引发的耐药● 肿瘤微环境(TME)：基质细胞通过CXCL12/CXCL13及整合素(如VLA-4)提供生存信号，激活PI3K/AKT通路增强肿瘤细胞黏附与存活，绕过BTK抑制的凋亡信号。● 表观遗传与转录因子：如TCF4过表达在ABC-DLBCL中替代BTK激活PLCγ2，导致伊布替尼耐药。如EP300、MLL2突变，通过表观遗传机制维持肿瘤细胞存活，与CLL耐药相关。04BTK抑制剂与降解剂BTK抑制剂的临床应用● 第一代BTKIs(如伊布替尼)：用于CLL、MCL、WM等，显著延长患者生存期。但存在脱靶效应(如抑制EGFR、TEC)导致出血、房颤等毒性，60%患者因C481S突变耐药。● 第二代BTKIs(如阿卡替尼、泽布替尼)：选择性更高，毒性更低，因安全性优势逐渐替代伊布替尼。阿卡替尼不抑制ITK和EGFR，房颤发生率低于伊布替尼，用于CLL/SLL和MCL。泽布替尼在CLL中ORR更高，但仍面临L528W等突变耐药。Tirabrutinib(日本获批用于PCNSL)、Orelabrutinib(中国获批用于R/RCLL/MCL)。● 第三代BTKIs(如吡托布鲁替尼)：可克服C481S突变耐药，对野生型和突变型BTK均有抑制作用。用于C481S突变的复发患者，但需警惕非C481突变(如L528W、T474I)导致交叉耐药。Fenebrutinib(用于RA、SLE)、Nemtabrutinib(针对C481S突变)处于II/III期试验。表2 已上市的BTKIs药物清单表3 目前正在进行临床试验的BTKIs药物清单BTK的靶向新策略：蛋白降解剂(PROTACs)● 作用机制及优势：通过双功能分子连接BTK配体与E3泛素连接酶，诱导BTK泛素化并经蛋白酶体降解，而非单纯酶抑制。可降解突变型BTK，且降解效率高，初步显示对耐药突变有效，但长期安全性尚需验证。图8 BTK降解剂作用机理● 代表药物与临床进展：1)NX-2127：降解BTK野生型及C481S、L528W突变体，同时降解IKZF1/3(增强T细胞功能)。I期试验显示，在复发CLL中缓解率33%，BTK降解率达86%。2)NX-5948：选择性降解BTK，血脑屏障穿透性强，用于中枢神经系统淋巴瘤，I期显示良好的耐受性和BTK降解效果。3)BGB-16673：I/II期数据显示在R/RCLL中可快速降低BTK水平，部分患者达部分缓解，但需警惕A428D突变导致的耐药。● 联合疗法：BTK降解剂与其他靶向药物(如BCL-2抑制剂)联用可能克服PLCγ2突变等非BTK依赖耐药机制。05BTK在不同疾病中的病理机制淋巴瘤● 原发性中枢神经系统淋巴瘤(PCNSL)PCNSL高频突变的MYD88和CD79B可异常激活BCR通路，使肿瘤细胞高度依赖BTK存活。BTKIs通过阻断PLCγ2，抑制肿瘤细胞增殖并诱导凋亡。此外，BTKIs还可调节肿瘤微环境，减少免疫逃逸，与免疫检查点抑制剂联用可增强抗肿瘤免疫应答。表4 用于PCNSL的BTKIs的临床试验● 慢性淋巴细胞白血病(CLL)BTK参与调节CLL细胞与肿瘤微环境的相互作用，影响疾病的进展。BTKIs可阻断BCR信号传导，诱导肿瘤细胞凋亡，同时调节免疫微环境，减少Treg细胞、增强CD8+T细胞功能并抑制巨噬细胞M2极化。图9 CLL细胞及其环境中的BTK抑制● 套细胞淋巴瘤(MCL)在MCL中，持续激活的BCR-BTK信号通路可促进MCL细胞的增殖和存活，影响肿瘤的发展。同时，BTK还与MCL细胞的黏附、迁移等过程相关，影响肿瘤细胞在体内的弥散。● 弥漫大B细胞淋巴瘤(DLBCL)在ABC型DLBCL中，BTK的持续激活可导致NF-κB通路的过度活化，驱动肿瘤细胞的生长和存活。然而在GCB型DLBCL中，BTK的依赖性相对较低。研究表明，部分DLBCL患者中存在BTK基因的扩增，与疾病的侵袭性和不良预后相关。伊布替尼单药治疗客观缓解率不高且无进展生存期短，目前多探索联合治疗方案。● 华氏巨球蛋白血症(WM)BTK的激活可促进WM细胞的存活、增殖以及免疫球蛋白的分泌。有研究显示，WM患者中常见的MYD88突变可增强BTK的活性，进一步促进肿瘤细胞的生长。伊布替尼、泽布替尼均获批用于WM治疗，客观缓解率较高。表5 已发表的针对CLL/SLL、MCL、WM、MZL的共价BTKIs表6 用于CLL/SLL、MCL、WM、MZL的非共价BTKIs和降解剂自身免疫性疾病● 自身免疫性水疱病BTK激活B细胞产生抗桥粒芯蛋白(如Desmoglein)的IgG抗体，破坏皮肤细胞间黏附，导致水疱形成；同时激活固有免疫细胞(如中性粒细胞、肥大细胞)，释放蛋白酶和炎症介质，加重表皮损伤。Rrilzabrutinib在II期试验中快速控制病情，减少糖皮质激素用量，尤其适用于抗桥粒芯蛋白抗体介导的自身免疫性水疱病。表7 自身免疫性水疱病临床前和临床试验中测试的BTKIs● 系统性红斑狼疮(SLE)BTK促进B细胞过度产生抗核抗体，形成免疫复合物沉积于肾脏、皮肤等组织，激活补体系统并诱发组织损伤；同时调控T细胞极化，促进Th1/Th17型免疫反应。在小鼠模型中，BTKIs可减少抗核小体抗体和组蛋白抗体，抑制DC和巨噬细胞过度活化，改善狼疮肾炎，但对抗dsDNA抗体影响有限，在人类II期试验中(如Fenebrutinib、Evobrutinib)疗效也有限。表8 系统性红斑狼疮临床前和临床试验中测试的BTKIs● 类风湿关节炎(RA)BTK在滑膜巨噬细胞和破骨细胞中激活，促进IL-6、MMPs等因子分泌，导致关节炎症、软骨破坏和骨侵蚀。B细胞通过BCR信号分泌类风湿因子(RF)和抗瓜氨酸化蛋白抗体(ACPA)，加剧自身免疫反应。BTKIs可抑制B细胞活化和抗体产生，减少滑膜炎症。临床前模型显示，CGI1746、GDC-0834等可减轻关节损伤，但部分II期临床试验(如BMS-986142)未达主要终点。表9 类风湿性关节炎临床前和临床试验中测试的BTKIs● 干燥综合征(SS)BTK驱动B细胞异常增殖和自身抗体(如抗SSA/Ro、抗SSB/La)分泌，导致唾液腺和泪腺的炎症及功能障碍。固有免疫细胞(如DCs)通过TLR-BTK通路分泌趋化因子，招募免疫细胞至外分泌腺体。Remibrutinib和Tirabrutinib在早期试验中尝试调节B细胞和唾液腺炎症，但疗效尚未突破。表10 干燥综合征临床前和临床试验中测试的BTKIs● 多发性硬化(MS)BTK通过调控B细胞和髓系细胞参与神经炎症和脱髓鞘过程，此外，BTK可能通过调节B细胞代谢(如线粒体呼吸)影响其与T细胞的交互作用。BTKIs穿透血脑屏障，抑制中枢神经系统内B细胞和髓系细胞的BTK信号，减少促炎因子释放和自身抗体产生，从而减轻炎症和神经损伤。Evobrutinib、Tolebrutinib在II期试验中减少MRI病灶，改善神经功能。表11 在多发性硬化症和重症肌无力的临床前和临床试验中测试的BTKIs炎症性疾病● 慢性自发性荨麻疹(CSU)BTK通过FcεRI信号激活肥大细胞和嗜碱性粒细胞，促进IgE介导的组胺释放和炎症细胞浸润，导致风团和瘙痒。● 银屑病BTK调控中性粒细胞的BTK通路，维持氧化应激和炎症状态；同时激活γδT细胞分泌IL-17A，促进角质形成细胞过度增殖。● 哮喘BTK参与IgE-FcεRI介导的气道炎症，促进Th2型细胞因子(如IL-4、IL-13)分泌和嗜酸性粒细胞浸润，导致气道重塑和高反应性。表12 在银屑病、慢性自发性荨麻疹、特应性皮炎和哮喘的的BTKIs06BTK抑制剂的不良反应与安全性常见副作用● 出血：与BTK/TEC抑制导致血小板功能障碍相关(如伊布替尼引起瘀斑、鼻衄)。● 心血管事件：房颤(与CSK或PI3K信号抑制有关)，第二代抑制剂(如泽布替尼)风险较低。● 感染：抑制中性粒细胞和巨噬细胞的抗菌功能，增加曲霉、肺孢子菌等机会性感染风险，尤其在CLL患者中。● 皮肤毒性：出现皮疹(EGFR脱靶效应)、指甲改变(如伊布替尼)。表13 BTKIs的不良事件当前挑战● 毒性管理：需监测血小板功能、心电图及肝功能，权衡疗效与感染风险，尤其是长期用药患者。● 耐药监测：实时检测BTK突变选择合适的抑制剂类型以便及时地调整治疗方案。未来方向● 新型抑制剂开发：高选择性非共价抑制剂(如Vecabrutinib)、双功能降解剂(如LP-168)，覆盖耐药突变，减少脱靶毒性。● 联合疗法：BTKIs+免疫检查点抑制剂、CAR-T细胞疗法、JAK抑制剂或补体抑制剂联用，增强抗肿瘤免疫。● 早期干预与预防：探索BTKIs在癌前病变或高风险人群中的应用。抗体发现服务 & 产品01羊驼免疫&骆驼免疫—自建现代化养殖农场02万亿级天然抗体库产品—轻松DIY科研抗体03配套产品—助您轻松搭建基因工程抗体平台关于仁域生物成都仁域生物成立于2019年1月，是一家专注基因工程抗体技术和天然抗体库开发的公司，拥有优化的噬菌体展示抗体库技术和现代化的骆驼/羊驼养殖免疫基地。可为客户提供14天、100%成功率的先导抗体分子发现服务，彻底解决传统抗体定制的周期长、失败率高、成本高三大难题。目前已经成功完成300+靶点抗体筛选项目！protocol 获取 / 产品咨询邮箱｜find@renyubio.com电话｜19136178673地址｜成都市经开区科技产业孵化园关注我们，小编将持续更新相关内容～参考文献Liu X, Lin Y, Zhuang Q, Deng H, Liu A, Sun J. BTK inhibitors resistance in B cell malignancies: Mechanisms and potential therapeutic strategies. Blood Rev. 2025 May;71:101273. Kim HO. BTK inhibitors and next-generation BTK-targeted therapeutics for B-cell malignancies. Arch Pharm Res. 2025 May 8. Grainger BT, Cheah CY. "The End of the Golden Weather": therapeutic strategies for mantle cell lymphoma relapsed or refractory to covalent BTK inhibitors. Haematologica. 2025 Mar 1;110(3):576-587. Gupta S, Sharma A, Shukla A, Mishra A, Singh A. From development to clinical success: the journey of established and next-generation BTK inhibitors. Invest New Drugs. 2025 Apr;43(2):377-393. Tian G, Chen Z, Wang B, Chen G, Xie L. Small-molecule BTK inhibitors: From discovery to clinical application. Bioorg Chem. 2025 Apr;157:108242. Salvaris RT, Brennan J, Lewis KL. BTK Is the Target That Keeps on Giving: A Review of BTK-Degrader Drug Development, Clinical Data, and Future Directions in CLL. Cancers (Basel). 2025 Feb 6;17(3):557. Xing Y, Zhao K, Zhang Y, Wang Y. BTK inhibition in primary central nervous system lymphoma: mechanisms, clinical efficacy, and future perspectives. Front Oncol. 2024 Dec 24;14:1463505.Bravo-Gonzalez A, Alasfour M, Soong D, Noy J, Pongas G. Advances in Targeted Therapy: Addressing Resistance to BTK Inhibition in B-Cell Lymphoid Malignancies. Cancers (Basel). 2024 Oct 10;16(20):3434. Jiang Q, Peng Y, Herling CD, Herling M. The Immunomodulatory Mechanisms of BTK Inhibition in CLL and Beyond. Cancers (Basel). 2024 Oct 23;16(21):3574. Tavakoli GM, Yazdanpanah N, Rezaei N. Targeting Bruton's tyrosine kinase (BTK) as a signaling pathway in immune-mediated diseases: from molecular mechanisms to leading treatments. Adv Rheumatol. 2024 Aug 21;64(1):61. Cool A, Nong T, Montoya S, Taylor J. BTK inhibitors: past, present, and future. Trends Pharmacol Sci. 2024 Aug;45(8):691-707.Mehra S, Nicholls M, Taylor J. The Evolving Role of Bruton's Tyrosine Kinase Inhibitors in B Cell Lymphomas. Int J Mol Sci. 2024 Jul 9;25(14):7516.Schaff L, Nayak L, Grommes C. Bruton's tyrosine kinase (BTK) inhibitors for the treatment of primary central nervous system lymphoma (PCNSL): current progress and latest advances. Leuk Lymphoma. 2024 Jul;65(7):882-894.Nawaratne V, Sondhi AK, Abdel-Wahab O, Taylor J. New Means and Challenges in the Targeting of BTK. Clin Cancer Res. 2024 Jun 3;30(11):2333-2341.

临床1期细胞疗法引进/卖出

2025-05-27

·Business Wire

BeOne Medicines Launches Following Redomiciliation to Switzerland, Marking a New Chapter in Global Oncology

SAN CARLOS, Calif. & BASEL, Switzerland--(BUSINESS WIRE)--BeOne Medicines Ltd. (NASDAQ: ONC; HKEX: 06160; SSE: 688235), a global oncology company formerly known as BeiGene, Ltd., today announced its new name and redomiciliation to Switzerland are officially in effect, marking a significant milestone in the Company’s evolution. “BeOne represents more than a name change—it’s not only a reflection of who we are today as a leading global oncology company, but also our ambition to redefine what’s possible in oncology as we unite patients, families, scientists, physicians, governments, and other oncology public health stakeholders around the world in our shared mission against cancer,” said John V. Oyler, Co-Founder, Chairman and CEO at BeOne. “While I know that our work is not done, I am extremely proud of the progress we have made with the explosive growth of BRUKINSA as the backbone of our hematology franchise, the expansion of our PD-1 inhibitor, TEVIMBRA, and our potentially transformative oncology pipeline of more than 50 investigational assets, one of the most prolific in the industry. After 15 years of relentless innovation and strategic investment to boost our internal global capabilities, we are just getting started, and I look forward to working together as BeOne.” The new name and redomiciliation to Switzerland from the Cayman Islands were approved by shareholders on April 28. The transition to the BeOne name across the Company’s worldwide operations on six continents will happen in phases. The redomiciliation to Switzerland strengthens BeOne’s presence and deepens its roots in a global biopharmaceutical hub, further enabling its growth strategy of bringing innovative medicines to patients around the world. Industry-Leading Innovation and Global Scale BeOne has built a differentiated and sustainable advantage through strategic investments to bolster its internal research, clinical development, and manufacturing capabilities. This unique model harnesses time and cost efficiencies to improve patient access, enables close oversight to enforce high standards across R&D and manufacturing, and safeguards our operational resilience for long-term growth. BRUKINSA has the broadest label in its treatment class and leads in new patient starts across all of its approved indications in the U.S. It also is the cornerstone of BeOne’s hematology franchise as a foundational treatment alongside late-stage BCL2 inhibitor sonrotoclax and potential first-in-class BTK protein degrader, BGB-16673, which was developed from the Company’s proprietary CDAC platform. BeOne also is focused on building future solid tumor franchises in breast, lung, and gastrointestinal cancers. By leveraging its platforms in multi-specific antibodies, protein degraders and antibody-drug conjugates, the Company is positioned to transform the future of oncology treatment. BeOne’s entrepreneurial research team, comprising more than 1,100 colleagues, advanced 13 new molecular entities into the clinic in 2024 alone, outpacing even the largest pharmaceutical companies. Further, its nearly 3,700-strong clinical development team has active or planned trials across more than 45 countries and regions, accelerating early-stage innovation through its “Fast to Proof-of-Concept” approach. To date, the Company has enrolled more than 25,000 patients in more than 170 trials, delivering speed and cost advantages that set it apart from industry peers. In addition, BeOne continues to expand its global manufacturing network with its $800 million flagship clinical R&D and manufacturing facility at the Princeton West Innovation Campus in Hopewell, N.J. This state-of-the-art site enables scalable production capacity to support the Company’s rapidly growing pipeline, operational resilience, and global ambitions. About BeOne BeOne Medicines, formerly known as BeiGene, is a global oncology company domiciled in Switzerland that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a portfolio spanning hematology and solid tumors, BeOne is expediting development of its diverse pipeline of novel therapeutics through its internal capabilities and collaborations. With a growing global team of more than 11,000 colleagues spanning six continents, the Company is committed to radically improving access to medicines for far more patients who need them. To learn more about BeOne, please visit www.beonemedicines.com and follow us on LinkedIn, X, Facebook and Instagram. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding BeOne’s ability to deliver transformative treatments to patients worldwide; the potential and future success of BeOne’s oncology pipeline; BeOne’s presence in Switzerland and its ability to enable further growth; the sustainable advantage of BeOne’s strategic investments and its ability to improve patient access; the future long-term growth of the Company; BeOne’s ability to transform the future of oncology treatment; and BeOne’s plans, commitments, aspirations and goals under the caption “About BeOne”. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeOne’s ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeOne’s ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeOne’s ability to obtain and maintain protection of intellectual property for its medicines and technology; BeOne’s reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeOne’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products; BeOne’s ability to obtain additional funding for operations and to complete the development of its drug candidates and maintain profitability; and those risks more fully discussed in the section entitled “Risk Factors” in BeOne’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeOne’s subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeOne undertakes no duty to update such information unless required by law. To access BeOne media resources, please visit our Newsroom.

2025-05-26

·药事纵横

特朗普“药品最惠国”价格标准落地，谁在欢呼，谁在颤抖？

5月20日，美国卫生与公众服务部（HHS）宣布正式实施特朗普总统的“药品最惠国”价格标准。政策要求制药企业将美国市场的药品定价与经合组织（OECD）中人均GDP至少为美国60%的国家的最低价格对齐，目标是让美国患者支付的药价“不再高于其他经济对等国家的患者”。根据HHS公布的细则，所谓“最惠国价格”并非简单对标全球最低价，而是设置了两道关键门槛：其一，参考国家限定为经合组织（OECD）成员国中人均GDP不低于美国60%的经济体，这直接排除了众多发展中国家；其二，仅针对尚无仿制药或生物类似药竞争的品牌原研药，这意味着大量专利到期药物被剔除在降价范围之外。举个例子，如果瑞士某抗癌药卖5000美元，法国卖3000美元，土耳其卖1000美元，但土耳其人均GDP不达标，那美国就盯着法国那个3000美元定价。要是药企敢在美国卖得比这高？政府直接出手砍价，甚至允许从加拿大、墨西哥等“低价区”进口药品来平抑价格。既避免了与印度、巴西等低价市场的直接比价，又保留了仿制药市场对原研药的价格制衡机制。从特朗普政府的政策逻辑来讲，美国长期承担全球最高药价，而同一款药物在其他发达国家的价格可能仅为美国的1/3至1/5。比如说治疗糖尿病的利拉鲁肽注射液在美国售价高达1000美元，而欧洲国家普遍在200-300美元区间。这种价差被特朗普称为“美国患者的不公平负担”，而“最惠国定价”则是要将美国药价直接拉平至全球最低水平，终结“美国补贴全球”的现状。政策一出，制药行业的反对声音立刻高涨。在价格标准还未出来之前，也就是特朗普刚提出这个计划时，就遭到了大量的质疑和反对。美国药品研究与制造商协会（PhRMA）首席执行官乌布尔直指这是“对创新的宣战”，他算了一笔账：若新规全面实施，行业未来十年收入将缩水1.2万亿美元，相当于抹去整个生物制药领域过去五年的研发投入。价格标杆一旦确立，商业保险支付方必将跟进压价，届时降价潮将从政府医保蔓延至整个市场,如果美国市场利润骤减，药企可能被迫削减研发预算，转向低风险的仿制药或“微创新”药物，最终导致重大疾病领域的突破性疗法减少。有反对也有支持，对于需要长期服用抗癌药的晚期患者而言，若价格从每月1.2万美元直降至4000美元，无异于生命延续的希望。另外，也不乏有人认为药企拿阻碍创新药研发说事存在夸大之嫌，美国很多企业的大量利润通过海外子公司避税，并未充分反哺本土研发。此外，HHS强调新政策“通过确保美国患者负担不高于他国来维护创新”，暗示药企需压缩营销和中间环节成本，如药品福利管理者PBM的回扣体系，而非单纯挤压研发。虽然确定了价格标准，但能否真正具体实施，或者说能否长久有效实施还得另说。2020年特朗普曾推出类似政策，但因越权干预市场被法院驳回。此次政策虽细化了对OECD国家的参考标准，但仍面临制药行业发起的宪法诉讼，总统是否有权绕过国会强制定价？若政策最终被判定违宪，那么川普再次让大家看了一场精彩的作秀。特朗普政策的全球性外溢效应，对中国医药行业，短期来看，有一定的负面影响。近年来，中国创新药“出海”势头迅猛，君实生物的PD-1单抗、和黄医药的呋喹替尼等产品在美定价高达国内的24-33倍，价差主要源于海外市场对研发成本的覆盖及支付能力差异。若美国强制药企降低本土售价，可能倒逼其通过提高其他市场售价维持利润。中国创新药若想进入欧美市场，或面临更严苛的定价谈判，甚至被要求同步降价，挤压中国药企的溢价空间。特朗普的“美国优先”政策可能进一步收紧对华生物技术出口限制，阻碍中国获取基因编辑、精准医疗等前沿技术。同时，美国《生物安全法案》若落地，将限制联邦资金流向与中国有关联的医药研发机构，影响CXO企业的海外订单。药明生物等头部企业虽已启动“去地缘化”布局，但短期内的合规成本上升与客户流失风险难以避免。长期而言，是机会也是动力。外部技术封锁与市场准入壁垒，可能迫使中国药企摆脱“仿制依赖”，加大对First-in-class药物的研发投入。2023年，中国创新药License-out数量已达License-in的两倍，头部企业如百济神州的泽布替尼、传奇生物的CAR-T疗法已通过国际合作打开全球市场。政策压力下，自主创新、全球授权的模式或成为主流，推动中国从“原料药大国”向“创新药强国”转型。再者，若美国压低药价导致国际定价体系重构，中国或加速完善以价值为导向的医保谈判机制，平衡创新激励与可及性。面对美国市场的不确定性，中国药企可加大对“一带一路”新兴市场的开拓。比如东南亚、中东等地区人口基数大、医疗需求增长快，且监管环境相对宽松，适合中国疫苗、仿制药等优势产品落地。欧洲市场虽准入标准高，但其对成本控制的需求与中国供应链优势形成互补，可通过本土合作实现突破。特朗普的“最惠国定价”政策，表面是解决美国国内药价高企的民生问题，实则是通过行政手段重塑全球药品定价权。对中国而言，短期阵痛难免，但长期来看，唯有坚持创新自立、市场多元与规则共建，方能在全球医药产业变局中占据主动。信息来源：[1]https://www.phirda.com/artilce_38919.html?module=trackingCodeGenerator[2]http://vip.stock.finance.sina.com.cn/q/go.php/vReport_Show/kind/latest/rptid/800706329855/index.phtml[3]https://finance.eastmoney.com/a/202505123402382621.html药事纵横投稿须知：稿费已上调，欢迎投稿

专利到期生物类似药突破性疗法

100 项与泽布替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11422	泽布替尼	L01XE	DB15035

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
浆母细胞淋巴瘤	日本	BeiGene Ltd.	2024-12-27
滤泡性淋巴瘤	泰国	BeiGene Ltd.	2024-02-07
华氏巨球蛋白血症难治	泰国	BeiGene Ltd.	2024-02-07
复发性滤泡性淋巴瘤	欧盟	BeiGene Ireland Ltd.	2023-11-17
复发性滤泡性淋巴瘤	冰岛	BeiGene Ireland Ltd.	2023-11-17
复发性滤泡性淋巴瘤	列支敦士登	BeiGene Ireland Ltd.	2023-11-17
复发性滤泡性淋巴瘤	挪威	BeiGene Ireland Ltd.	2023-11-17
复发性边缘区淋巴瘤	美国	BeiGene Ltd.	2023-01-19
难治性边缘区淋巴瘤	巴西	BeiGene Ltd.	2022-11-10
难治性滤泡性淋巴瘤	英国	BeiGene Ltd.	2021-12-06
边缘区B细胞淋巴瘤	乌拉圭	BeiGene Ltd.	2021-04-28
巨球蛋白血症	加拿大	BeiGene Ltd.	2021-03-30
慢性淋巴细胞白血病	中国	百济神州（苏州）生物科技有限公司	2020-06-03
小淋巴细胞淋巴瘤	中国	百济神州（苏州）生物科技有限公司	2020-06-02
套细胞淋巴瘤	美国	BeiGene Ltd.	2019-11-14

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
膜性肾小球肾炎	临床3期	美国	百济神州（苏州）生物科技有限公司	2023-04-17
膜性肾小球肾炎	临床3期	中国	百济神州（苏州）生物科技有限公司	2023-04-17
膜性肾小球肾炎	临床3期	阿根廷	百济神州（苏州）生物科技有限公司	2023-04-17
膜性肾小球肾炎	临床3期	巴西	百济神州（苏州）生物科技有限公司	2023-04-17
膜性肾小球肾炎	临床3期	加拿大	百济神州（苏州）生物科技有限公司	2023-04-17
膜性肾小球肾炎	临床3期	捷克	百济神州（苏州）生物科技有限公司	2023-04-17
膜性肾小球肾炎	临床3期	意大利	百济神州（苏州）生物科技有限公司	2023-04-17
膜性肾小球肾炎	临床3期	波兰	百济神州（苏州）生物科技有限公司	2023-04-17
膜性肾小球肾炎	临床3期	土耳其	百济神州（苏州）生物科技有限公司	2023-04-17
膜性肾小球肾炎	临床3期	英国	百济神州（苏州）生物科技有限公司	2023-04-17

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AACR2025	N/A	B细胞淋巴瘤 BTK V416L	-	Zanubrutinib	淵簾膚獵壓齋窪範築簾(願餘膚蓋膚鹹構壓夢願) = 齋選積鑰鹹鏇餘窪鏇製製廠夢遞鏇艱築鹹觸顧 (繭鏇醖鏇廠襯築廠獵淵 )	积极	2025-04-30
				Acalabrutinib	淵簾膚獵壓齋窪範築簾(願餘膚蓋膚鹹構壓夢願) = 遞膚廠築簾鬱鏇憲積鹽製廠夢遞鏇艱築鹹觸顧 (繭鏇醖鏇廠襯築廠獵淵 )
NCT06375733 (Company_Website) 人工标引	临床2期	弥漫性大B细胞淋巴瘤	9	SLS009 (tambiciclib) in combination with Zanubrutinib	壓鹹壓製鏇網繭醖鹹選(鑰觸製鏇餘艱製蓋鏇選) = 蓋廠餘築繭壓艱網獵構醖選醖襯窪鑰襯蓋壓簾 (鏇壓廠糧襯醖製鹽簾築 ) 更多	积极	2025-02-20
				SLS009 (tambiciclib) in combination with Zanubrutinib (Difficult-to-Treat Non-GCB)	蓋鹽衊願繭壓觸觸齋顧(艱構鑰壓鑰衊鏇蓋衊壓) = 鑰範構齋範糧範淵鑰願艱網糧構襯憲鏇糧鬱艱 (簾衊遞壓構願獵淵觸糧 )
NCT03734016 (ALPINE, Pubmed \| Blood)	临床3期	慢性淋巴细胞白血病 del(17p) \| TP53 mutation	652	Zanubrutinib	蓋鹹築蓋構衊糧願構夢(築夢窪壓網窪醖廠鬱壓) = no cardiac deaths were reported with zanubrutinib vs 6 cardiac deaths with ibrutinib 選顧糧壓鹹繭簾繭簾築 (蓋鏇餘願範鹽壓觸鏇構 ) 更多	积极	2024-12-26
				Ibrutinib
NCT04116437 (BGB-3111-215, ASH2024) 人工标引	临床2期	套细胞淋巴瘤 \| 慢性淋巴细胞白血病 \| 巨球蛋白血症 ... 更多	35	Zanubrutinib	鏇構鹽蓋餘鹽網夢鬱鹽(壓遞製遞積鑰餘範鏇憲) = 網鬱膚壓願鏇餘鬱築顧廠淵鹽構憲簾艱淵膚蓋 (襯蓋醖衊鹽壓繭鬱醖襯 ) 更多	积极	2024-12-09
ASH2024 人工标引	临床1期	弥漫性大B细胞淋巴瘤	22	Polatuzumab Vedotin+Zanubrutinib+Rituximab+Lenalidomide	鏇製製壓願構鬱構製獵(鏇繭鬱鑰鏇範淵膚蓋願) = 繭鹹鏇艱製艱觸鑰選網餘艱齋鑰鹽糧蓋遞願鑰 (繭糧齋糧簾醖願廠淵繭 ) 更多	积极	2024-12-09
NCT04277637 (BGB-11417-101, ASH2024) 人工标引	临床1期	慢性淋巴细胞白血病	112	zanubrutinib + Sonrotoclax 160 mg	窪鬱鬱餘齋築衊獵糧繭(簾鏇鹽壓製簾衊醖簾鏇) = neutropenia (41%), contusion (38%), COVID-19 (30%), and diarrhea (29%; 78% had grade 1 events). Neutropenia was the most common grade ≥3 TEAE (n=29, 26%). 範範遞齋廠廠顧構遞選 (鹽觸鏇觸遞範壓夢範網 )	积极	2024-12-09
				zanubrutinib + Sonrotoclax 320 mg
ASH2024	N/A	慢性淋巴细胞白血病	-	Zanubrutinib 160 mg	願憲衊獵鹹憲鹹醖觸獵(繭鏇築願衊夢襯觸艱鬱) = 繭願鹹繭簾範糧膚餘醖築蓋簾窪餘淵鹹餘憲願 (蓋製鏇範積窪鏇夢鹽簾 ) 更多	-	2024-12-09
ChiCTR2100054552 (ASH2024)	临床4期	弥漫性大B细胞淋巴瘤	-	ZR-CHOP	鹽夢衊壓願簾夢襯廠鬱(鏇遞壓廠構鹽糧餘衊鑰) = 92.9% of patients experienced any-grade treatment emergent adverse events (TEAEs), with the majority being hematological toxicities 繭壓範遞艱膚窪窪築餘 (壓鬱網鹽鹽網壓簾窪鹽 ) 更多	-	2024-12-09
ASH2024	N/A	弥漫性大B细胞淋巴瘤	-	Zanubrutinib 160 mg	糧襯製築餘簾艱繭齋選(積夢獵製鹽壓壓齋遞顧) = Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 74% of patients; the most common TEAEs were neutrophil count decreased (58%), white blood cell count decreased (29%), and lymphocyte count decreased (20%). TEAEs led to treatment discontinuation in 7 patients (11%) and death in 2 patients (3%; cardiopulmonary failure, n=1; pneumonia, n=1; neither considered related to study treatment) 齋衊簾築範襯襯獵衊構 (願襯鏇艱糧鏇窪憲簾襯 )	-	2024-12-09
				Lenalidomide 25 mg
ASH2024	N/A	滤泡性淋巴瘤	-	Zanubrutinib plus Obinutuzumab	構憲醖蓋繭築夢製網淵(範齋膚顧選憲糧願膚顧) = 選廠糧繭觸憲鏇齋齋壓淵鏇繭醖醖夢獵築獵鑰 (襯夢壓糧齋壓齋獵壓繭, 16.1 ~ NE)	-	2024-12-08
				Obinutuzumab alone	構憲醖蓋繭築夢製網淵(範齋膚顧選憲糧願膚顧) = 憲觸夢艱壓鹽製選襯淵淵鏇繭醖醖夢獵築獵鑰 (襯夢壓糧齋壓齋獵壓繭, 6.5 ~ 13.8)