This phase II trial studies how well the addition of nemtabrutinib to lisocabtagene maraleucel in treating patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Nemtabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lisocabtagene maraleucel is a type of treatment called chimeric antigen receptor (CAR) T-cell therapy, in which a patient's T-cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T-cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T-cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T-cells are grown in the laboratory and given to the patient by infusion for treatment. Adding nemtabrutinib to lisocabtagene maraleucel may be an effective treatment for relapsed/refractory CLL/SLL.

开始日期2025-12-01

申办/合作机构

Fred Hutchinson Cancer Research Center

[+1]

NCT06863402

/ Recruiting临床2期IIT

Nemtabrutinib and Pembrolizumab in Patients With Richter Transformation: A Phase II Study

This phase II trial tests how well nemtabrutinib in combination with pembrolizumab works in treating patients with Richter transformation, diffuse large B-cell lymphoma subtype (RT-DLBCL). Nemtabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cells (a type of white blood cell) in cancers such as Richter transformation at abnormal levels. This may help keep cancer cells from growing and spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving nemtabrutinib in combination with pembrolizumab may kill more cancer cells in patients with RT-DLBCL.

开始日期2025-11-15

申办/合作机构

Roswell Park Comprehensive Cancer Center

NCT06572618

/ Recruiting临床2期IIT

A Phase 2 Study of BTK Inhibitor Nemtabrutinib in Combination With Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma

This phase II trial tests how well nemtabrutinib works with rituximab for the treatment of patients with mantle cell lymphoma. Nemtabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantel cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving nemtabrutinib with rituximab may kill more cancer cells in patients with mantle cell lymphoma.

开始日期2025-01-22

申办/合作机构

City of Hope National Medical Center

[+1]

100 项与 Nemtabrutinib 相关的临床结果

登录后查看更多信息

100 项与 Nemtabrutinib 相关的转化医学

登录后查看更多信息

100 项与 Nemtabrutinib 相关的专利（医药）

登录后查看更多信息

项与 Nemtabrutinib 相关的文献（医药）

2025-05-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design, synthesis, and biological evaluation of novel BTK-targeting proteolysis targeting chimeras (PROTACs) with enhanced pharmacokinetic properties

Article

作者: Su, Huahua ; Yu, Xufen ; Liu, Jing ; Cao, Tao ; Lin, Ying ; Tian, Xinjian ; Xiang, Jianpin ; Wang, Yonghui ; Xie, Qiong ; Wang, Jin

Bruton's tyrosine kinase (BTK) has been an attractive target in the B-cell malignancies. Significant progress has been achieved in developing effective BTK-targeting small-molecule inhibitors and proteolysis targeting chimeras (PROTACs). Based on noncovalent inhibitor ARQ-531, we previously developed two potent BTK PROTACs 6e and SC-3e, which exhibited poor pharmacokinetic property. Herein, we present our extensive structure-activity relationship (SAR) studies focused on BTK binder, linker and cereblon (CRBN) ligand of SC-3e, resulting in two novel BTK PROTACs FDU28 (compound 25) and FDU73 (compound 27). Compounds 25 and 27 selectively induced rapid and robust degradation of wild type (WT) and C481S mutant BTK in a concentration-, time- and ubiquitin-proteasome system (UPS)-dependent manner without affecting CRBN neo-substrates. Furthermore, compound 27 displayed excellent cell antiproliferative activities, metabolic stability in mouse liver microsomes and improved bioavailability in mice. Overall, 27 is a highly effective and selective BTK degrader that is suitable for in vivo efficacy investigations.

2025-04-11·ACS Pharmacology & Translational Science

Comprehensive Characterization of Bruton’s Tyrosine Kinase Inhibitor Specificity, Potency, and Biological Effects: Insights into Covalent and Noncovalent Mechanistic Signatures

Review

作者: Servant, Nicole B. ; King, Alastair J. ; Jahic, Mirza ; Darragh, Antonia C. ; Lipner, Justin H. ; Hanna, Andrew M.

Uncovering a drug's mechanism of action and possible adverse effects are critical components in drug discovery and development. Moreover, it provides evidence for why some drugs prove more effective than others and how to design better drugs altogether. Here, we demonstrate the utility of a high-throughput in vitro screening platform along with a comprehensive panel to aid in the characterization of 15 Bruton's tyrosine kinase (BTK) inhibitors that are either approved by the FDA or presently under clinical evaluation. To compare the potency of these drugs, we measured the binding affinity of each to wild-type BTK as well as a clinically relevant resistance mutant of BTK (BTK C481S). In doing so, we discovered a considerable difference in the selectivity and potency of these BTK inhibitors to the wild-type and mutant proteins. Some of this potentially contributes to the adverse effects experienced by patients undergoing therapy using these drugs. Overall, noncovalent BTK inhibitors showed stronger potency for both the wild-type and mutant BTK when compared with that of covalent inhibitors, with the majority demonstrating a higher specificity and less off-target modulation. Additionally, we compared biological outcomes for four of these inhibitors in human cell-based models. As expected, we found different phenotypic profiles for each inhibitor. However, the two noncovalent inhibitors had fewer off-target biological effects when compared with the two covalent inhibitors. This and similar in-depth preclinical characterization of drug candidates can provide critical insights into the efficacy and mechanism of action of a compound that may affect its safety in a clinical setting.

2024-11-01·CHEMICO-BIOLOGICAL INTERACTIONS

Discovery of new non-covalent reversible BTK inhibitors: Synthesis, in silico studies, and in vitro evaluations

Article

作者: Zeng, Shenxin ; Huang, Wenhai ; Xu, Xiangwei ; Wang, Wenyong ; Zhang, Chixiao ; Chi, Xinglong ; Wang, Zunyuan ; Pan, Youlu ; Kang, Youkun ; Wang, Shu

Bruton's Tyrosine Kinase (BTK) played a key role in the B cell antigen receptor (BCR) signaling pathway, and was considered a hotspot in the treatment of B cell malignant tumors and B cell immune diseases. There were 5 covalent irreversible inhibitors launched currently on the market, but C481S mutation was detected in most patients after administration. The approval of Pirtobrutinib (Jaypirca) by FDA in 2023 aroused great interest in the development of non-covalent and reversible BTK inhibitors. In order to solve the resistance of covalent irreversible inhibitors caused by C481S mutation, 11 reversible BTK inhibitors were designed based on screening in this article. The design, synthesis, in silico studies, and in vitro evaluations were performed for further verification. Among them, compound WS-11 showed best activity with IC₅₀ of 3.9 nM for wild type, 2.2 nM for C481S mutation BTK, which was comparable to the positive control Pirtobrutinib. Furthermore, WS-11 would have a good druglikeness properties predicted by pkCSM and SwissADME, which provided a promising lead for further optimization and development.

项与 Nemtabrutinib 相关的新闻（医药）

2025-10-09

·BiG生物创新社

诺华甩出自免“新王炸”

作者｜momo 诺华向来步履坚定，敢于在自免领域押注全新机制。10月1日，诺华旗下的高选择性口服BTK抑制剂Remibrutinib正式获得FDA批准上市，标志着BTK靶向治疗在自免领域迈入收获阶段。上一个被诺华成功推向巅峰的FIC药物司库奇尤单抗，已成为自免领域的现象级产品。如今，随着Remibrutinib的获批，诺华在慢性自发性荨麻疹（CSU）赛道筑起先发优势，下一个“司库奇尤单抗”，或许已在路上。 01 肿瘤明星靶点在肿瘤治疗领域，BTK已成为一个备受瞩目的明星靶点。BTK作为一种非受体酪氨酸激酶，广泛参与B细胞的发育与活化过程。在生理状态下，BTK介导B细胞受体信号传导，调控细胞的生存与增殖；然而，当B细胞发生癌变时，BTK会异常活化，持续传递促生长信号，驱动肿瘤细胞的增殖、迁移和存活，从而促进B细胞恶性肿瘤的发展，如慢性淋巴细胞白血病、套细胞淋巴瘤等。 BTK 抑制剂（BTKi）通过作用于 BCR 信号通路（图1），与 BTK 特异性结合而抑制 BTK 自身磷酸化，阻止 BTK 激活，从而阻断下游信号通路的激活，最终诱导肿瘤细胞凋亡。图1.BCR信号通路 2013年，首款BTKi伊布替尼获FDA批准上市，改变了边缘区淋巴瘤（MZL）、MCL、华氏巨球蛋白血症（WM）及CLL等血液瘤的治疗格局。然而其选择性差，还抑制EGFR、TEC等多个靶点，存在脱靶毒性，导致皮疹、房颤、腹泻、高血压等副作用。为克服第一代药物的局限性，第二代BTKi应运而生。阿可替尼、泽布替尼等药物通过优化分子结构，提高了对BTK的选择性，在保持疗效的同时显著降低了脱靶毒性。其中，泽布替尼凭借卓越的临床数据，成为全球首个且目前唯一在CLL/SLL“头对头”研究中在PFS与ORR上均取得优效性的新一代BTKi，力证自身BIC地位。然而，临床实践中仍存在约30%的患者因BTK C481S位点突变而对共价BTKi产生耐药，这一挑战催生了第三代BTKi的研发。2023年获批的吡托布鲁替尼作为首个上市的三代药物，采用可逆共价结合机制，能够有效克服C481S突变导致的耐药问题。表1.全球已上市 BTK 抑制剂礼来正通过多项头对头III期研究，探索吡托布鲁替尼在套细胞淋巴瘤和慢性淋巴细胞白血病中相较于现有疗法的优势。与此同时，默沙东开发的奈他布替尼也进入III期临床阶段，其II期研究在多种B细胞肿瘤中显示出颇具潜力的疗效，进一步丰富耐药患者的治疗选择。除了小分子抑制剂的迭代创新，蛋白质降解靶向嵌合体技术的应用为BTK靶点治疗开辟了新方向。BTK PROTAC通过募集E3泛素连接酶，诱导BTK蛋白泛素化降解，从而彻底清除靶蛋白，理论上能够更彻底地解决耐药问题。百济神州开发的BGB-16673已进入III期临床，其I期CaDAnCe-101研究数据显示，经过大量前期治疗的CLL患者ORR达到78%，在200mg剂量组更飙升至94%；华氏巨球蛋白血症（WM）患者ORR为90%，边缘区淋巴瘤（MZL）患者ORR更是达到100%。2025年5月，百济神州启动了BGB-16673与吡托布鲁替尼头对头CaDAnCe 304研究，将进一步验证PROTAC技术的治疗潜力。 02 开启自免新大陆自免疾病作为仅次于肿瘤的全球第二大药物市场，正成为药企竞相争夺的“黄金赛道”。近年来，BTKi作为一类具有多重作用机制的小分子靶向药物，正逐步向自免领域拓展，开辟出一片“新大陆”。然而，最初BTKi在自免领域的探索并非一帆风顺。默沙东的Evotrutinib、罗氏的Fenebrutinib、赛诺菲的Tolebrutinib等项目曾因疗效不足或肝毒性等问题在临床后期遭遇暂停（图2）。后续随着对BTK机制理解的深化，企业开始在特定适应症上实现突破。据不完全统计，目前全球针对自免疾病的在研BTKi已超过33款，高度聚焦于多发性硬化症、自发性荨麻疹、系统性红斑狼疮和类风湿性关节炎。图2.用于自免适应症的BTK抑制剂和降解剂结构诺华的Remibrutinib作为新一代共价BTKi，通过结合BTK的非活性构象，展现出高选择性。而全球首款BTKi伊布替尼虽在肿瘤治疗中表现优异，却因脱靶毒性在自免领域受限。其开发者艾伯维转而开发新型BTKi Elsubrutinib，并与JAK抑制剂乌帕替尼组成复方制剂ABBV-599，探索系统性红斑狼疮治疗新路径。赛诺菲通过收购Principia Biopharma，获得Rilzabrutinib和Tolebrutinib两款核心资产，成为BTK自免领域的领跑者。其中，Rilzabrutinib已于今年8月获FDA批准用于免疫性血小板减少症，成为该领域首个获批的BTKi，并已在国内提交新药申请。其适应症正拓展至自身免疫性溶血性贫血、特应性皮炎等。 Tolebrutinib在2022年由于多例跟药物相关的肝损伤事件，被FDA暂停部分MS和重症肌无力的III期研究，后续通过更新入组标准、定期肝功能监测等措施，得以继续临床研究。凭借其脑穿透性优势，精准靶向多发性硬化症的神经炎症机制，Tolebrutinib已向FDA提交针对nrSPMS的上市申请，有望成为该疾病首个BTKi。赛诺菲预测，这两款药物年销售额均有望达到20亿-50亿欧元，未来或成公司增长引擎。令人振奋的是，中国药企在这一赛道展现出强劲竞争力。其中，诺诚健华的奥布替尼在免疫性血小板减少症的Ⅲ期研究已完成患者入组，预计2026年提交上市申请，有望成为首个申报自身免疫适应症的国产BTKi；同时，其在多发性硬化、系统性红斑狼疮等疾病的全球多中心研究也同步推进。百济神州的泽布替尼则凭借2024年全球26.44亿美元的销售额跻身全球畅销药榜单，其自免适应症布局涵盖嗜血细胞性淋巴组织细胞增多症、免疫性血小板减少症、冷凝集素病等多个领域，其中部分适应症已在国内完成Ⅲ期试验。此外，BGB-16673也已在自免领域启动慢性自发性荨麻疹的Ⅰ期研究（图2）。 03 首款，自免“新王炸” 慢性自发性荨麻疹（CSU）是一种由免疫失调驱动的疾病，主要表现为肥大细胞和嗜碱性粒细胞的异常激活，进而通过免疫球蛋白E（IgE）或免疫球蛋白G（IgG）通路触发BTK信号级联反应。这一过程导致组胺和其他促炎介质的释放，引发患者反复出现瘙痒性风团、血管性水肿等症状，严重损害生活质量。尽管H1抗组胺药作为一线治疗被广泛使用，但约60%的患者在用药后症状仍无法充分控制，凸显了临床需求的未满足性。BTK作为组胺释放的核心酶，在CSU发病机制中扮演关键角色，因此靶向BTK成为突破治疗瓶颈的新方向。诺华开发的Remibrutinib作为首款高选择性、口服靶向BTK的第二代共价抑制剂，展现出“新王炸”的潜力。该药物通过精准抑制BTK的活性，阻断下游的免疫级联反应，从而有效阻止组胺释放，缓解瘙痒、荨麻疹和肿胀等核心症状，为CSU治疗提供新希望。 Remibrutinib针对慢性自发性荨麻疹的REMIX-1/2 两项III期临床试验结果显示：与安慰剂相比，Remibrutinib在治疗第12周时显著改善每周荨麻疹活动度评分（UAS7）（图3）、每周瘙痒严重程度评分（ISS7）和每周风团数量评分（HSS7），且这种疗效持续至第24周。更值得注意的是，药物起效迅速，治疗第1周即可观察到症状减轻；到第24周时，半数患者症状得到控制，约30%患者瘙痒和荨麻疹完全消失。图3.REMIX-1/2试验UAS7评分降幅对比安全性方面，Remibrutinib未出现转氨酶升高相关的肝损伤风险，最常见的不良事件（发生率≥3%）包括上呼吸道感染、瘀点、头痛等。且患者无需持续实验室监测，这为其长期使用提供了便利。基于上述临床试验的积极结果，Remibrutinib于2025年2月和3月先后在中国和美国递交上市申请，并于10月1日获得美国FDA批准，用于H1抗组胺药控制不佳的CSU成人患者，成为首个获FDA认可用于CSU的BTKi。同时，诺华已向欧盟、日本和中国等全球监管机构提交申请，并在中国获得优先审评资格。此外，诺华还在开发Remibrutinib用于治疗荨麻疹、多发性硬化、化脓性汗腺炎、重症肌无力等适应症。诺华预测其年销售额峰值有望超过 30 亿美元。结语 Remibrutinib的获批，是诺华在自免版图上插下的一面旗帜，诺华以BTK为支点，撬动整个自免治疗格局，从肿瘤战场到自免新域，BTK抑制剂的故事远未终结。参考资料 [1]https://www.nature.com/articles/s41375-020-01072-6 [2]https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-rhapsido-remibrutinib-only-oral-targeted-btki-treatment-chronic-spontaneous-urticaria-csu [3]https://www.nejm.org/doi/full/10.1056/NEJMoa2408792 [4]https://www.fiercepharma.com/pharma/standing-alone-novartis-bumps-its-growth-projection-through-end-decade [5]长江证券、财通证券研报共建Biomedical创新生态圈！如何加入BiG会员？

上市批准临床3期临床2期临床结果蛋白降解靶向嵌合体

2025-09-08

·Firstwordpharma

Lilly touts Jaypirca's "striking" survival results in new front-line CLL study

Eli Lilly said Monday that its blood cancer drug Jaypirca (pirtobrutinib) extended progression-free survival (PFS) significantly longer than chemoimmunotherapy in newly diagnosed patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma (CLL/SLL).Results from the Phase III BRUIN CLL-313 study show "one of the most compelling effect sizes ever" seen for a single-agent BTK inhibitor in the front-line setting, according to the company.The randomised trial enrolled 282 untreated CLL/SLL patients without 17p deletions and found that Jaypirca produced a "highly statistically significant and clinically meaningful improvement" in PFS when compared to bendamustine plus rituximab, hitting the primary endpoint. Overall survival (OS) results were not yet mature at the interim analysis, but were "trending strongly" in Jaypirca's favour. A final OS readout is expected in 2026.Jacob Van Naarden, president of Lilly Oncology, called the findings "striking and provocative, across both PFS and OS endpoints… With this third positive Phase III study, we continue to build the clinical evidence supporting the possible role of [Jaypirca] in a variety of CLL/SLL treatment settings, including treatment-naïve, BTK inhibitor-naïve and BTK inhibitor exposed."The drug's safety profile mirrored earlier studies and was generally consistent across treatment settings. Detailed results will be presented at a medical congress and submitted to a peer-reviewed journal.Jaypirca — a highly selective, non-covalent BTK enzyme inhibitor — was granted accelerated approvals in 2023 for third-line CLL/SLL and mantle cell lymphoma after at least one other BTK inhibitor. Lilly is looking to move the drug, which brought in $337 million last year, earlier in the treatment algorithm.Monday's findings follow encouraging readouts from two other late-stage CLL trials. In BRUIN CLL-314, which included a cohort of treatment-naïve patients, Jaypirca showed non-inferior response rates against AbbVie and Johnson & Johnson's covalent BTK inhibitor Imbruvica (ibrutinib), with PFS trending positively (see – KOL Views Q&A: Front-line CLL data chip away at bias that Lilly's Jaypirca belongs behind covalent BTK inhibitors). Prior to that, BRUIN CLL-321 demonstrated that Jaypirca was superior to investigator's choice of treatment, cutting the risk of relapse, disease progression or death by 46% in patients previously treated with at least one covalent BTK inhibitor.Lilly says BRUIN CLL-313 and BRUIN CLL-314 will form the basis of its planned global submissions later this year.Meanwhile, Merck & Co. is advancing its own non-covalent BTK inhibitor, nemtabrutinib, though it trails Jaypirca in development. The drug is in several Phase III studies, including BELLWAVE-011, which pits it against Imbruvica and AstraZeneca's Calquence (acalabrutinib) in first-line CLL/SLL. That study is slated for completion in the second half of 2032, according to ClinicalTrials.gov.

临床3期临床结果加速审批临床2期

2025-08-30

·药明康德

致敬时代 | 近90%患者癌细胞减少或几乎“全消失”！无需再依赖化疗，多款新型抗癌药为这类患者点亮希望

编者按：2025年，药明康德迎来创立25周年的重要里程碑。值此契机，我们向所有与我们共同书写产业变革篇章的科学家、医药人和投资者致以衷心感谢与诚挚敬意，也特别推出“致敬时代”系列，回顾全球同仁如何借助科学与合作的力量，不断拓展治疗边界、改善患者命运。四分之一个世纪的坚守，只为加速每一款新药的诞生。下一个25年，我们将继续心怀感恩与敬畏，依托独特的CRDMO模式，与全球伙伴携手同行，共赴健康未来。白血病是威胁人类生命的常见恶性血液肿瘤之一。但有一种白血病偶尔被人们称为“最轻的白血病”，那就是慢性淋巴细胞白血病（简称慢淋，CLL）。这是一种成熟B淋巴细胞克隆增殖性肿瘤，表现为外周血淋巴细胞增多。慢淋常见于中老年患者，大致可分为两类，有一种生长非常缓慢，患者往往无明显症状，在很长一段时间里不需药物治疗，只需定期找医生随诊；另一种则生长更快、也更严重。尤其是出现耐药和复发的患者，将面临更差的预后。在欧美国家，慢淋是最常见的白血病类型，大约占白血病总体患者的25%～30%。虽然慢淋在亚洲人群里发生率相对较低，但检出率及诊断率也在逐步上升。到目前为止，慢淋唯一可根治的手段就是异基因造血干细胞移植，但不幸的是，很多患者因为年龄、身体状况、供者等各方面原因，没机会接受这样的治疗。因此对大多数慢淋患者来说，治疗的目标是带病生存，能够长期维持在一个比较好的生活状态。图片来源：123RF 直到20世纪中叶，各类白血病依然缺乏有效的治疗手段。20世纪40年代，科学家们发现氮芥对慢性白血病等血液肿瘤有积极作用，白血病自此进入化疗时代。50~70年代，苯丁酸氮芥和环磷酰胺等烷化剂类药物的研发，让慢淋患者获得了30%~40%的缓解率。80~90年代，氟达拉滨等嘌呤类似物成为慢淋的主要治疗手段，让缓解率提升至50%左右。但化疗带来的细胞毒性等问题，依然影响着患者的生活质量。进入21世纪后，慢淋治疗有了非常大的突破，从传统的化疗走向了以靶向治疗为主的时代，还有层出不穷的新型治疗方案正改变着慢淋治疗的版图。作为全球医药及生命科学行业值得信赖的合作伙伴和重要贡献者，药明康德在25年发展历程中，很荣幸见证了多款慢淋新疗法从实验室到临床的突破历程，更通过提供一体化、端到端的新药研发和生产服务，助力全球合作伙伴加速多款慢淋创新疗法的研发进程，造福病患。今天这篇文章将再次回望近25年来慢淋新疗法的攻坚历程，向那些以勇气、坚持与热爱迎难而上的人们致敬。单克隆抗体疗法：开启靶向时代世纪之交，单克隆抗体疗法率先打破了慢淋治疗主要依赖化疗的局面。其中一个重要靶点是CD20。这是一种B细胞分化抗原，在95%以上的B细胞性淋巴瘤中表达，而在造血干细胞、血浆细胞和其他正常组织中不表达。 1997年，基因泰克（现为罗氏旗下子公司）与渤健共同开发的靶向CD20的利妥昔单抗（rituximab，商品名：Rituxan）问世，随后在各类癌症治疗领域都发挥了重要作用，也包括慢淋。科学家发现，利妥昔单抗与氟达拉滨等化疗药物联用比先后单独使用两款药物效果更好。2010年，利妥昔单抗的新适应症获FDA批准，与氟达拉滨和环磷酰胺联合用于治疗初治和既往经治的CD20阳性慢淋患者。利妥昔单抗的成功，也启发产业不断迭代以CD20为目标的单抗药物，例如由Genmab公司与诺华联合开发的第二代CD20单抗代表药物奥法妥木单抗（ofatumumab）。它是一款全人源化单抗，其结合的表位也与利妥昔单抗不同，主要用于对其它治疗或其它单抗不再有应答的患者。2009年，奥法妥木单抗获FDA批准（商品名：Arzerra），用于对氟达拉滨和阿仑珠单抗耐药的慢淋患者。如今，这两款药物均已成为慢淋的主要治疗药物。由GlycArt Biotechnology、罗氏旗下基因泰克与渤健共同开发、2013年获FDA批准用于慢淋的奥妥珠单抗（obinutuzumab，商品名：Gazyva）属于第三代CD20抗体。与前两款药物相比，它杀死慢淋细胞更直接、作用更强，并且早期试验已证实了该药可快速将B细胞从外周血细胞中清除出去。它可与化疗药物或靶向药物伊布替尼一起作为慢淋初治疗法，也可单独治疗复发或对其它治疗无应答的慢淋。除了上述几种单抗，还有针对CD52抗原的单抗药物阿仑珠单抗（alemtuzumab，商品名：Lemtrada）。它由拜耳与赛诺菲共同开发，2001年获美国FDA批准用于治疗对烷化剂和氟达拉滨耐药的进展期慢淋。 BTK抑制剂：伊布替尼惊艳问世，同类靶向药多点开花说到近十多年慢淋靶向疗法的发展，就不得不提到布鲁顿氏酪氨酸激酶（BTK）抑制剂。其中一款重磅新药战绩尤其辉煌，让慢淋化疗成为了历史——它，就是伊布替尼（ibrutinib），一度被称为“慢淋领域的格列卫”。这款新药背后，有着跌宕起伏的研发历程。 20世纪90年代，一种后来被命名为BTK的酪氨酸激酶进入了科学家的视野。BTK被发现在B细胞受体（BCR）信号通路中起着关键作用；而在慢淋的癌细胞里，BTK蛋白水平会出现异常升高。 BTK自然成为了B细胞恶性肿瘤中富有吸引力的一个治疗靶点，很多公司开始针对BTK设计具有激酶选择性的抑制剂，其中也包括Celera Genomics公司。 21世纪初，Celera公司在探索中孕育了一款靶向BTK并与之共价结合的小分子。由于共价药物可与人体内蛋白非选择性、不可逆、永久结合，一旦脱靶结合到正常的人体蛋白上，可能引起严重的毒副作用，这种潜在风险使共价药物一度成为药物研发的禁忌。因此，Celera公司最初并没有把它作为候选药物，而只是当作“工具化合物”协助BTK抑制剂的筛选。 2006年，一家名为Pharmacyclics的公司收购了这款在Celera公司没能得到充分重视的小分子。Pharmacyclics当时的首席执行官、血液肿瘤专家理查德·米勒（Richard Miller）博士敏锐地意识到了它在B细胞癌症中的潜力。尽管他和团队在B细胞淋巴瘤动物模型中证实了这款药物的活性，但很多研发人员对这款共价结合机制的药物仍然持犹疑态度。然而，很多患者正在死亡的边缘。米勒博士不愿意因为对“共价机制”的风险担忧，而让这些患者无止境地等下去。 2009年，这款小分子的1期临床试验启动了。2011年，Pharmacyclics公司报告了它在1b/2期试验中用于一系列B细胞恶性肿瘤的积极数据，不久后，强生旗下杨森制药（现更名为强生创新制药）也宣布与Pharmacyclics进行合作，共同研发这款新药。 2013年11月，以“伊布替尼”之名，这款不负众望的新药获FDA加速批准上市（商品名：Imbruvica）用于套细胞淋巴瘤的治疗。同一时期，它在慢淋中也表现出惊人的疗效，并在2014年2月获得FDA批准用于既往至少接受过一种治疗的慢淋患者。后续发表于2015年的3年随访结果显示，伊布替尼单药治疗就让90%的慢淋既往经治患者和84%的初治患者获得缓解，达到完全缓解的患者分别占7%和23%，总缓解率为88%。也就是说，近90%的患者肿瘤细胞数明显下降或几乎“全消失”。这是一个激动人心的结果，意味着患者可以摆脱对化疗的依赖。图片来源：123RF 更长期的8年随访研究表明，在经治和初治的慢淋患者中，伊布替尼的总缓解率分别高达89%和87%，分别有10%和35%的患者获得完全缓解，中位无进展生存期分别长达52个月和尚未达到，7年总生存率分别达到55%和84%。 2015年，艾伯维以高达210亿美元的金额收购了拥有伊布替尼的Pharmacyclics，与强生共同继续伊布替尼的研究工作。2016年3月，FDA批准了伊布替尼的第5个适应症，单药用于慢淋患者的一线治疗。这是FDA批准的首个“无化疗”慢淋一线治疗方案，意味着伊布替尼可替代化疗作为慢淋的一线治疗选择，是一个重要的里程碑。在推动此次获批的3期临床试验中，与化疗组相比，接受伊布替尼单药治疗的初治慢淋患者总缓解率达到82.4%，是前者（35.3%）的2倍多，无进展生存期显著延长，疾病进展或死亡风险降低84%。如今，伊布替尼已获FDA批准治疗10余项适应症，并成为多种血液肿瘤的一线治疗选择。目前伊布替尼已在全球100多个国家和地区获批，惠及全球超30万患者。此后，更多BTK靶向药物接连问世，让包括慢淋在内的B细胞恶性肿瘤患者的生活迎来了巨大改善。已获FDA批准的BTK抑制剂还包括由百济神州研发的泽布替尼（zanubrutinib），由礼来、Redx Pharma与LOXO Oncology共同开发、可破解共价BTK抑制剂耐药困局的首个非共价（可逆）BTK抑制剂匹妥布替尼（pirtobrutinib），以及由阿斯利康与Acerta Pharma共同开发的阿可替尼（acalabrutinib）。在中国获批用于慢淋的BTK抑制剂还有由诺诚健华与渤健共同研发的奥布替尼。其它靶向抑制剂：瞄准更多靶点随着医药科技的进步，还有更多重要靶点被发现、更多新的重磅药物诞生。与BTK类似，PI3K蛋白在多种B细胞恶性肿瘤中也存在过度表达的现象，而抑制PI3K不仅会影响BCR信号通路，还会对炎症、细胞信号传导和血管生成产生抑制，从而影响与肿瘤增殖有关的微环境。由ICOS与吉利德共同开发的艾代拉利司（idelalisib，商品名：Zydelig）是第一代口服PI3K-delta抑制剂。它于2014年获FDA批准上市治疗复发/难治性慢淋。它临床活性显著，可诱导细胞凋亡、抑制恶性B细胞系/原发肿瘤细胞系增殖，还能阻断多种信号通路，降低肿瘤细胞的生存能力。由Infinity Pharmaceuticals和Verastem共同开发的度恩西布（duvelisib，商品名：Copiktra）则是一款口服PI3K-delta和PI3K-gamma双重抑制剂。它于2018年获FDA批准用于治疗此前至少使用两种其它疗法的成人复发/难治性慢淋。其对PI3K-delta的抑制导致恶性肿瘤细胞凋亡，而对PI3K-gamma的抑制则减少了肿瘤微环境中支持细胞的分化和转移。 B细胞淋巴瘤因子-2（BCL-2）也是一个重要靶点。BCL-2可阻止细胞凋亡，并在某些类型癌症中过度表达，与耐药性的形成相关。比如由艾伯维与罗氏旗下基因泰克共同开发的维奈克拉（venetoclax，商品名：Venclexta），就是一种口服、选择性BCL-2抑制剂，通过选择性抑制BCL-2的功能，恢复细胞的通讯系统，让癌细胞自我毁灭，达到治疗肿瘤的目的。2016~2019年，维奈克拉先后获FDA批准了多项慢淋相关适应症。今年还有一款在中国获批慢淋适应症的BCL-2抑制剂——由亚盛医药研发的利沙托克拉。探索仍在继续过去25年间，美国FDA共批准了至少14款治疗慢淋的新疗法，除上述药物之外，还有2008年获批的化疗药物苯达莫司汀（bendamustine，商品名Treanda），以及2024年获批的靶向CD19的CAR-T细胞疗法lisocabtagene maraleucel（liso-cel，商品名Breyanzi）。药明康德很高兴能为其中多款疗法提供赋能、助力合作伙伴的这些创新疗法来到全球患者身边。为更好地提高慢淋患者的生活质量、解决药物长期使用带来的耐药等问题，产业圈仍在携手努力。当下还有近200款针对慢淋的新疗法正处于积极的临床研究中，有望在未来造福更多患者。其中多款药物已进入3期临床阶段，涵盖小分子靶向药和靶向蛋白降解剂等多种类型。比如由默沙东与ArQule共同研发的nemtabrutinib，近期研究证实其对BTK抑制剂耐药（包括携带BTK C481S突变）的复发或难治性慢淋患者有效，且在TP53异常亚组中仍有疗效，安全性可控。目前科学家正在进行一项3期试验，以评估这款新药对比维奈克拉+利妥昔单抗联合疗法的疗效。在抗击慢淋的漫漫旅途中，这些令人兴奋的成就源于科学家敢于挑战传统的洞见和勇气，也离不开转化医学中来自学术界和产业界的携手努力。最后，让我们再次向那些在慢淋治疗领域不懈探索的英雄们致以崇高的敬意。药明康德也期待与业界同仁继续同行，助力让更多创新疗法来到患者身边。参考资料： [1] Ponader, S., & Burger, J. A. (2014). Bruton's tyrosine kinase: from X-linked agammaglobulinemia toward targeted therapy for B-cell malignancies. Journal of clinical oncology, 32(17), 1830-1839. https://doi.org/10.1200/JCO.2013.53.1046 [2] The Wild Story Behind A Promising Experimental Cancer Drug. Retrieved Aug 27, 2025, from https://www.forbes.com/sites/davidshaywitz/2013/04/05/the-wild-story-behind-a-promising-experimental-cancer-drug/ [3] 打造一“键”封喉的共价抗癌药——专访北大深圳研究生院潘峥婴博士. Retrieved Aug 27, 2025, from https://www.wuximediaglobal.com [4] Pharmacyclics. Retrieved Aug 27, 2025 from https://www.pharmacyclics.com/home/who-we-are/history [5] Byrd, J. C., Furman, R. R., Coutre, S. E., Flinn, I. W., Burger, J. A., Blum, K. A., ... & O'Brien, S. (2013). Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. New England Journal of Medicine, 369(1), 32-42. DOI: 10.1056/NEJMoa1215637 [6] Johnson & Johnson, Pharmacyclics, Inc. Breakthrough Drug Wins FDA Approval. Retrieved Aug 27, 2025, from https://www.biospace.com/article/releases/johnson-and-johnson-pharmacyclics-inc-breakthrough-drug-wins-fda-approval-/ [7] The drug that may make chemo a thing of the past. Retrieved Aug 27, 2025, from https://www.mdanderson.org/publications/conquest/spring-2014/the-drug-that-may-make-chemo-a-thing-of-the-past.html [8] New Drug Application (NDA): 205552. Retrieved Aug 27, 2025 from https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=205552 [9] 西安杨森. Retrieved Aug 27, 2025 from https://www.xian-janssen.com.cn/ [10]上海合全药业2018年度报告. Retrieved Aug 27, 2025 from http://pdf.dfcfw.com/pdf/H2_AN201903221308711829_1.pdf [11] AbbVie Completes Acquisition of Pharmacyclics. Retrieved Aug 27, 2025 from https://investors.abbvie.com/news-releases/news-release-details/abbvie-completes-acquisition-pharmacyclics [12] Ozcan, M., Lavie, D., Chaudhry, A., Zhou, X., Paydar, I., Farooqui, M. Z., & Ghia, P. (2024). BELLWAVE-010: A phase 3 study of nemtabrutinib plus venetoclax versus venetoclax plus rituximab (VR) in previously treated patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).https://doi.org/10.1200/JCO.2024.42.16_suppl.TPS7089 [13] Thomas, X. (2013). First contributors in the history of leukemia. World Journal of Hematology, 2(3), 62-70. doi: 10.5315 / wjh.v2.i3.62 [14] Mehranfar, S., Zeinali, S., Hosseini, R., Akbarzadeh, A., Mohammadian, M., & Feizi, A. H. P. (2017). History of leukemia: diagnosis and treatment from beginning to now. Galen Medical Journal, 6(1), e702-e702. DOI: https://doi.org/10.31661/gmj.v6i1.702 [15] Innovation of CLL Treatments: Chemotherapy Era - HealthTree for Chronic Lymphocytic Leukemia. Retrieved Aug 27, 2025 from https://healthtree.org/cll/community/articles/innovation-cll-treatment-chemotherapy-era [16] Rai, K. R., & Jain, P. (2016). C hronic lymphocytic leukemia (CLL)—Then and now. American journal of hematology, 91(3), 330-340. https://doi.org/10.1002/ajh.24282 [17] Perez-Carretero, C., Gonzalez-Gascon-y-Marin, I., Rodriguez-Vicente, A. E., Quijada-Alamo, M., Hernandez-Rivas, J. A., Hernandez-Sanchez, M., & Hernandez-Rivas, J. M. (2021). The evolving landscape of chronic lymphocytic leukemia on diagnosis, prognosis and treatment. Diagnostics, 11(5), 853. doi: 10.3390/diagnostics11050853 [18] 慢性淋巴细胞白血病/小淋巴细胞淋巴瘤诊疗指南（2022年版）. Retrieved Aug 27, 2025 from https://www.nhc.gov.cn/yzygj/c100068/202204/0c1f7d3aca0545abbeb02030ce255930/files/1732863055385_61833.pdf [19] Troubled Infinity licenses cancer drug to Verastem | BioPharma Dive）. Retrieved Aug 27, 2025 from https://www.biopharmadive.com/news/Infinity-duvelisib-verastem-license/429724/ [20] 中国抗癌协会血液肿瘤专业委员会,中华医学会血液学分会,中国慢性淋巴细胞白血病工作组,(2025). 中国慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的诊断与治疗指南（2025年版）. 中华血液学杂志,46(02)：105-112.DOI:10.3760/cma.j.cn121090-20241209-00551 [21]IMBRUVICA® (ibrutinib) Pooled Outcomes Data from Three Phase 3 Studies Suggest Potential Clinical Efficacy in Patients with High-Risk Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) . Retrieved Aug 27, 2025 from https://www.prnewswire.com/news-releases/imbruvica-ibrutinib-pooled-outcomes-data-from-three-phase-3-studies-suggest-potential-clinical-efficacy-in-patients-with-high-risk-chronic-lymphocytic-leukemiasmall-lymphocytic-lymphoma-cllsll-300457242.html [22]de Claro, R. A., McGinn, K. M., Verdun, N., Lee, S. L., Chiu, H. J., Saber, H., ... & Pazdur, R. (2015). FDA approval: ibrutinib for patients with previously treated mantle cell lymphoma and previously treated chronic lymphocytic leukemia. Clinical Cancer Research, 21(16), 3586-3590. [23] Byrd, J. C., Furman, R. R., Coutre, S. E., Burger, J. A., Blum, K. A., Coleman, M., ... & O'Brien, S. (2015). Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood, The Journal of the American Society of Hematology, 125(16), 2497-2506. https://doi.org/10.1182/blood-2014-10-606038 [24] Byrd, J. C., Furman, R. R., Coutre, S. E., Flinn, I. W., Burger, J. A., Blum, K., ... & O'Brien, S. (2020). Ibrutinib treatment for first-line and relapsed/refractory chronic lymphocytic leukemia: final analysis of the pivotal phase Ib/II PCYC-1102 study. Clinical Cancer Research, 26(15), 3918-3927. https://doi.org/10.1158/1078-0432.CCR-19-2856 [25] IMBRUVICA® (ibrutinib) Approved by U.S. FDA for the First-line Treatment of Chronic Lymphocytic Leukemia. Retrieved Aug 27, 2025 from https://news.abbvie.com/2016-03-04-IMBRUVICA-ibrutinib-Approved-by-U-S-FDA-for-the-First-line-Treatment-of-Chronic-Lymphocytic-Leukemia [26] The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy | PNAS. Retrieved Aug 27, 2025 from https://www.pnas.org/doi/10.1073/pnas.1004594107 [27] Byrd, J. C., Blum, K. A., Burger, J. A., Coutre, S. E., Sharman, J. P., Furman, R. R., ... & O'Brien, S. M. (2011). Activity and tolerability of the Bruton's tyrosine kinase (Btk) inhibitor PCI-32765 in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Interim results of a phase Ib/II study. Journal of Clinical Oncology, 29(15_suppl), 6508-6508. [28] Phase Ib/II Study of the Activity and Tolerability of the Bruton’s Tyrosine Kinase Inhibitor PCI-32765 in CLL/SLL | Research To Practice. Retrieved Aug 27, 2025 from https://www.researchtopractice.com/index.php?q=5MJCASCO2011/CLL/1 [29] Pharmacyclics Forms Pact to Develop and Commercialize PCI-32765 for Hematologic Cancers with Janssen Biotech, Inc. (prnewswire.com) . Retrieved Aug 27, 2025 from https://www.prnewswire.com/news-releases/pharmacyclics-forms-pact-to-develop-and-commercialize-pci-32765-for-hematologic-cancers-with-janssen-biotech-inc-135271818.html [30] Advani, R. H., Buggy, J. J., Sharman, J. P., Smith, S. M., Boyd, T. E., Grant, B., ... & Fowler, N. H. (2012). Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. Journal of Clinical Oncology, 31(1), 88-94. doi: 10.1200/JCO.2012.42.7906 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床研究

100 项与 Nemtabrutinib 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
B细胞淋巴瘤	临床3期	美国	Merck Sharp & Dohme LLC	2023-08-08
B细胞淋巴瘤	临床3期	阿根廷	Merck Sharp & Dohme LLC	2023-08-08
B细胞淋巴瘤	临床3期	澳大利亚	Merck Sharp & Dohme LLC	2023-08-08
B细胞淋巴瘤	临床3期	比利时	Merck Sharp & Dohme LLC	2023-08-08
B细胞淋巴瘤	临床3期	巴西	Merck Sharp & Dohme LLC	2023-08-08
B细胞淋巴瘤	临床3期	加拿大	Merck Sharp & Dohme LLC	2023-08-08
B细胞淋巴瘤	临床3期	智利	Merck Sharp & Dohme LLC	2023-08-08
B细胞淋巴瘤	临床3期	哥伦比亚	Merck Sharp & Dohme LLC	2023-08-08
B细胞淋巴瘤	临床3期	法国	Merck Sharp & Dohme LLC	2023-08-08
B细胞淋巴瘤	临床3期	德国	Merck Sharp & Dohme LLC	2023-08-08

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04728893 (BELLWAVE-003, EHA2025)	临床2期	难治性滤泡性淋巴瘤	49	Nemtabrutinib 65 mg PO QD	窪顧壓艱衊鏇網窪膚膚(觸窪鏇範餘鹹選獵願憲) = Any-grade adverse events (AEs) occurred in 45 participants (92%) 鑰衊繭製鹽鏇襯鑰築獵 (觸壓鹹憲衊衊鬱壓鹽齋 ) 更多	积极	2025-05-14
NCT04728893 (BELLWAVE-003, EHA2025)	临床2期	难治性边缘区淋巴瘤	-	Nemtabrutinib 65 mg QD	壓範衊構遞顧構襯鑰鏇(繭艱齋築壓鬱鏇簾糧憲) = 20 pts (91%) experienced any grade adverse events (AEs) 憲鏇襯願壓衊夢襯餘鹽 (選構觸壓獵選憲觸遞顧 ) 更多	积极	2025-05-14
NCT04728893 (BELLWAVE-003, ASH2024) 人工标引	临床2期	边缘区B细胞淋巴瘤	12	Nemtabrutinib 65 mg	憲製繭廠範築壓壓齋壓(網廠獵憲構齋壓壓製繭) = 鹽積壓壓膚淵壓觸衊鑰築餘繭鏇選蓋糧糧襯網 (壓顧範鹽壓蓋壓繭蓋壓, 31 ~ 89) 更多	积极	2024-12-08
ASH2024	N/A	滤泡性淋巴瘤	-	Nemtabrutinib 65 mg once daily	鹽積鹽範獵襯願選鹽齋(獵願簾蓋醖遞鏇鹽膚壓) = Any-grade adverse events (AEs) occurred in 31 (86%) pts, most commonly neutropenia in 10 (28%) pts, decreased platelet count (8 [22%], and anemia (7 [19%]) 範襯遞衊構觸壓齋觸蓋 (壓夢鏇觸醖觸壓醖鑰簾 ) 更多	-	2024-12-07
NCT03162536 (MK-1026-001, Pubmed) 人工标引	临床1期	慢性淋巴细胞白血病 \| B细胞淋巴瘤三线 C481S mutant BTK	47	nemtabrutinib 65 mg	鏇衊糧廠淵餘簾鏇範廠(願築構淵憲網獵構築淵) = 範鑰壓窪鑰艱糧顧夢蓋繭簾獵夢壓鏇鑰鬱壓襯 (製衊簾鬱積壓淵獵餘製 ) 更多	积极	2024-01-12
NCT03162536 (BELLWAVE-001, ICML2023)	临床1/2期	B细胞淋巴瘤 C481S-mutant BTK	112	Nemtabrutinib 65 mg	鑰製構廠蓋網鬱網鬱鏇(壓選襯廠網顧選選憲鏇) = 願製窪鏇繭廠艱襯憲蓋糧齋築餘衊觸築鏇壓選 (糧窪壓齋夢鬱蓋窪構淵, 42 ~ 69) 更多	积极	2023-06-09
NCT04728893 (MK-1026-003 \| 1026-003 \| BELLWAVE-003, ASCO2023)	临床2期	血液肿瘤	450	Nemtabrutinib 80 mg QD	獵壓繭網艱獵網壓遞鏇(鹽膚廠壓醖簾衊憲遞願) = 膚鹽鑰觸餘築醖鏇積繭鹽糧憲製願鹹窪廠構艱 (糧鏇鹽選遞網齋窪窪鹹 )	-	2023-05-31
	临床2期	血液肿瘤	450	Nemtabrutinib 65 mg QD	獵壓繭網艱獵網壓遞鏇(鹽膚廠壓醖簾衊憲遞願) = 膚製鬱鬱鹽齋簾觸齋膚鹽糧憲製願鹹窪廠構艱 (糧鏇鹽選遞網齋窪窪鹹 )	-	2023-05-31
NCT03162536 (1026-001 \| ARQ 531-101 \| Bellwave-001 \| MK-1026-001, ASH 12022 \| ASH 22022) 人工标引	临床1/2期	慢性淋巴细胞白血病三线	57	Nemtabrutinib (CLL/SLL)	獵範膚鹹衊憲夢淵廠鹽(鹹艱糧壓簾獵願築簾製) = 艱積構遞獵繭網簾製餘積窪膚廠鏇選鑰鹽觸鹽 (願衊窪繭顧製鹹範鑰襯, 42 ~ 69) 更多	积极	2022-11-15
	临床1/2期	慢性淋巴细胞白血病三线	57	Nemtabrutinib (overall)	願憲餘淵築鑰蓋鏇蓋願(壓齋獵鹹繭顧繭構鹽鑰) = 糧構簾選衊選繭鏇構簾積蓋餘艱壓壓鏇夢觸簾 (積願製窪窪觸蓋艱選觸 ) 更多	积极	2022-11-15
NCT03162536 (1026-001 \| ARQ 531-101 \| BELLWAVE-001 \| MK-1026-001, EHA2022)	临床2期	慢性淋巴细胞白血病	118	Nemtabrutinib	蓋艱艱蓋壓築淵襯餘淵(衊鑰鹽鹹鬱淵觸糧膚糧) = 網襯鹹齋鏇積製網遞築築壓獵襯醖鏇鏇齋淵夢 (餘選選選觸選膚糧構範 )	-	2022-05-12
NCT03162536 (1026-001 \| ARQ 531-101 \| MK-1026-001, AACR2018)	临床1期	慢性淋巴细胞白血病	-	ARQ 531	齋餘遞觸齋觸醖獵壓醖(醖繭觸鏇鑰蓋網鑰夢鹽) = 製網遞憲鏇廠鏇廠構蓋艱鏇衊簾構網淵願壓願 (鹹蓋憲蓋廠網衊網簾襯 )	-	2018-07-01