This phase II trial tests the safety and side effects of glofitamab and obinutuzumab and how well they work in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory) after receiving CD19-directed chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a form of immunotherapy where the immune system cell, T-cell, is changed to attack cancer cells. Glofitamab is a bispecific antibody that can bind to two different antigens at the same time. Glofitamab binds to CD3, a protein found on T cells (a type of white blood cell), and CD20 a protein found on B cells (another type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving glofitamab and obinutuzumab may be safe, tolerable, and/or effective in treating patients with relapsed or refractory mantle cell lymphoma after receiving CD19-directed CAR T-cell therapy.

开始日期2025-10-31

申办/合作机构

National Cancer Institute

NCT06922604

/ Not yet recruiting临床1期IIT

A Phase 1b Study of Glofitamab in CNS Lymphoma

This phase Ib trial tests the safety and side effects of glofitamab after pre-treatment with obinutuzumab and how well they work in treating patients with central nervous system (CNS) lymphoma. Glofitamab is a bispecific antibody that can bind to two different antigens (substances that cause the body to make a specific immune response) at the same time. Glofitamab binds to CD20 on lymphoma cells, and CD3 on T-cells (a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Obinutuzumab can also be administered as a pre-treatment to make glofitamab safer and more tolerable. Giving glofitamab with obinutuzumab pre-treatment may be safe, tolerable, and/or effective in treating patients with CNS lymphoma.

开始日期2025-09-23

申办/合作机构

City of Hope National Medical Center

[+1]

NCT06994169

/ Not yet recruitingN/AIIT

Glofitamab in Real Life

To date, more than 300 patients have been treated with Glofitamab in the Expanded Access Programme (EAP) in France. In this study, it is proposed to perform a retrospective analysis of some of these patients. The aim is to describe the efficacy and safety of Glofitamab in the largest reported real-world cohort, with an expected median follow-up of more than 9 months. Particular focus will be given to the relapsed or refractory chimeric antigen receptors-T (CAR-T) population to confirm the response rates (CRR: 35-39%) of Glofitamab in this population and to assess the optimal timing of therapy initiation [8, 15].

开始日期2025-08-01

申办/合作机构

Le LYSARC

100 项与格菲妥单抗相关的临床结果

登录后查看更多信息

100 项与格菲妥单抗相关的转化医学

登录后查看更多信息

100 项与格菲妥单抗相关的专利（医药）

登录后查看更多信息

项与格菲妥单抗相关的文献（医药）

2025-12-31·JOURNAL OF MEDICAL ECONOMICS

Budget impact of introducing glofitamab for treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy in the United States

Article

作者: Li, Jia ; Mahmoudjafari, Zahra ; Masaquel, Anthony ; Parisé, Hélène ; Bercaw, Eric ; Bognar, Katalin ; Wang, Si-Tien

BACKGROUND:

Glofitamab is a T-cell engaging bispecific monoclonal antibody that was granted accelerated approval from the United States Food and Drug Administration for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, after ≥2 lines of systemic therapy (3L+).

METHODS:

A budget impact model was developed for a hypothetical blended commercial/Medicare health plan with 1,000,000 members. Comparators were axicabtagene ciloleucel (Axi-cel), lisocabtagene maraleucel (Liso-cel), tisagenlecleucel (Tisa-cel), loncastuximab tesirine, polatuzumab vedotin + bendamustine + rituximab, rituximab + gemcitabine + oxaliplatin, tafasitamab + lenalidomide, and epcoritamab (Epcor). Total costs included those for drugs, wastage, administration, grade ≥3 adverse reactions, and all-grade cytokine release syndrome) and routine care. Market shares were based on internal projections and expert opinions. Total and per-member per-month (PMPM) net budget impacts over 3 years were calculated.

RESULTS:

Approximately nine patients were projected to be eligible for 3L + DLBCL treatment in a health plan of 1,000,000 members. The introduction of glofitamab as a treatment option resulted in estimated total and PMPM cost savings of $728,697 and -$0.0202, respectively, over 3 years. Costs were reduced across all cost categories but particularly in drug costs. Among the newer therapies, total 3-year cost per treated patient was lowest for glofitamab: $226,658 versus Tisa-cel = $564,113; Axi-cel = $540,002; Liso-cel = $516,272; and Epcor = $335,293. Across all sensitivity analyses, the inclusion of glofitamab had minimal PMPM budget impact, ranging from -$0.0256 to -$0.0108.

CONCLUSIONS:

With the lowest 3-year total cost per treated patient among the newer therapies, glofitamab being an available option in the 3L + DLBCL market is estimated to save a hypothetical 1,000,000-member health plan $728,697 in cumulative total costs and $0.0202 in PMPM costs over 3 years.

2025-08-01·CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Recent development in bispecific antibody immunotherapy for hematological malignancies

Review

作者: Wang, Ke ; Guo, Xuejun ; Han, Lijie ; Yu, Jifeng ; Jiang, Zhongxing

While monoclonal antibody (mAb)-based therapies have revolutionized cancer treatment, challenges such as resistance mechanisms and tumor progression via alternative pathways underscore the need for novel therapeutic strategies. Bispecific antibodies (BsAbs), which target two distinct antigens simultaneously, represent a promising next-generation solution, improving therapeutic precision, efficacy, and safety. BsAbs also redirect cytotoxic effector cells to tumor sites, providing additional therapeutic mechanisms. Recent advancements in BsAb design, such as enhancements in pharmacokinetics and modular multi-specific formats, are expanding their use in hematological malignancies. Combining BsAbs with immune checkpoint inhibitors and other therapies may overcome resistance and improve clinical outcomes. Leading BsAbs, including mosunetuzumab, glofitamab, and blinatumomab, have demonstrated promising efficacy in clinical trials for leukemia and lymphoma subtypes. Despite remaining challenges, particularly in acute myeloid leukemia (AML), ongoing research into new targets and combination therapies is expected to enhance the efficacy of BsAbs in relapsed or refractory (R/R) disease. This review explores the structural and functional innovations of BsAbs, the challenges in current therapies, and their transformative potential in hematological malignancy immunotherapy.

2025-06-01·CTS-Clinical and Translational Science

CD20×CD3 Bispecific Antibodies in B‐NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research

Review

作者: Davis, John D. ; Welf, Erik ; Zhu, Min ; Guan, Xiaowen ; Ganguly, Samit

ABSTRACT:

Despite advancements in treatment for B‐cell non‐Hodgkin lymphoma (B‐NHL) in recent decades, many patients still relapse or are refractory to treatment, which represents a high unmet medical need. Novel CD20 × CD3 T‐cell–engaging bispecific antibodies (bsAbs) have created a new paradigm for the treatment of B‐NHL. Pivotal studies of four CD20 × CD3 bsAbs, mosunetuzumab, glofitamab, epcoritamab, and odronextamab, as monotherapy, have demonstrated robust responses with generally manageable safety profiles in patients with relapsed or refractory follicular lymphoma and diffuse large B‐cell lymphoma after ≥ 2 lines of systemic therapy. These agents have presented unique challenges (e.g., cytokine release syndrome [CRS]), which have required different strategies to overcome. This review provides a comprehensive overview of the clinical development of these four CD20 × CD3 bsAbs that have been investigated for the treatment of B‐NHL, with a specific focus on translational assessments to select starting doses in first‐in‐human studies, management of CRS, application of modeling and simulation approaches to aid dose escalation and optimization/selection, and strategies used in the design of phase I–III clinical trials. By highlighting learnings and experiences from these four bsAbs assessed, which have not been summarized collectively elsewhere, we aim to promote more efficient study design for novel bsAbs in B‐NHL in the future.

429

项与格菲妥单抗相关的新闻（医药）

2025-06-12

·同写意

连环画：双特异性抗体

同写意年度巨献！！7月25-26日，邀您相聚金鸡湖畔，与5000人一起为中国医药创新“同写意”！1、双特异性或双靶点药物的崛起应和了如今药物研发的最大困境：小分子药和蛋白药的药物靶点不够用了。2006年时统计的已获批药物共针对324个药靶。2017年，已获批药物的药靶数量扩展到893个，其中667个是人蛋白。假设传统药物（不包括核酸药和细胞治疗）可开发的药靶共有1000个，所有生物技术和制药公司的共同竞争空间则受到极大的禁锢。但如果考虑双靶点药物的话，药靶空间（双药靶的随机组合数）增长了500倍。图片来源：参考资料132、双特异性抗体（这里简称双抗或bsAb）是最重要的一类双靶点药物，也是近些年来最热门的药物研发领域之一。它的研发历史已有几十年: 图中黄色的立柱代表和双抗有关的论文每年发表篇数（左轴），紫色的立柱代表每年进入临床试验的双抗数。到目前为止，已有三个双抗药获批，其中两个还在市场上（Amgen的Blincyto / Blinatumomab和Chugai的Hemlibra / Emicizumab），但有上百个双抗药分子正在临床试验中被评估。未来几年将是双抗药全面爆发的时代。3、双特异性抗体不等同于两种单克隆抗体的联合用药。和联合用药相比，双抗的优势包括单一的药代动力学特性（PK profile）和相对简单的申报流程：如果两种单抗在体内有不同的半衰期，在联合用药中需要平衡两者的给药时间表；联合用药在申报时需要准备两套CMC、毒理数据等。但双抗药最重要的优势是obligate effects，或全新功能。图片来源：参考资料144、如果一个双抗药的效果仅仅等同于（additive effects）或超过（synergistic effects）两种母单抗的联合用药产生的效果，它还不是最理想的双抗药。一个理想的双抗药可以产生全新的功能、全新的效果。如果这种新功能是两种母抗体不管如何联用也无法获得的，它就是obligate effects 。图片来源：参考资料185、双抗产生新功能主要有两个机理。第一个机理是通过空间重排产生新的药效（spatial obligate mechanisms）。在这种情况下，双抗同时结合两个药靶，把它们拉近，进而启动下一步行为。最常见的双抗——细胞桥接双抗——就是利用这个机理(a)。比如，T细胞导向双抗同时结合T细胞上的CD3和肿瘤细胞表面上的某种抗原（tumor associated antigen, TAA），桥接两种细胞，并激活T细胞，以杀死肿瘤细胞。还有的双抗，如b和c所示，同时结合同一细胞表面上的两种受体，或者导致细胞凋亡，或者促进细胞生长。这种效果只有在两种受体被交联时才会发生。Hemlibra则是d图描绘的双抗类型的一个例子：Hemlibra模仿FVIIIa因子，把FIXa和FX拉到一起，激活FX，引起血凝反应。图片来源：参考资料186、双抗产生新功能的第二个主要机理是在时间维度上完成的（temporal obligate mechanisms）。双抗分子先通过一个结合臂结合一个靶点，再因此被置换到新的空间（比如通过血脑屏障（图e），或被内吞入细胞（图f）），最后通过另一个结合臂结合第二个靶点，触发下游反应。如果第一个结合事件不发生，该双抗接触不到第二个靶点。从这个角度看，该双抗的第一个结合臂是第二个的递送装置。图片来源：参考资料147、图1中的499,500种双靶点组合只是可能的成药空间（双抗的成药空间比这要小的多）。理性设计只能找到寥寥不多的几种双抗。要从中找到更多的能产生新功能的组合需要一个高通量的筛选手段。对于双抗药来说，第一个难题是如何构建足够大的双抗分子库以供筛选。假设针对每个靶点有10种结合片段（binders）可供选择（覆盖不同的表位和亲和力），那么针对两个靶点就至少需要10 x 10 = 100种双抗分子。即使对大公司来说，制备、提纯100种蛋白分子也不是一件容易的事。这还只是在双靶点的成药空间中筛选。如果要从多靶点空间中寻找合适的双抗，制备的蛋白数量急剧增加。可以说，构建大规模的双抗分子库是双抗药研发的一个主要门槛。这里，我们以UCB的技术平台为代表来探讨一下制药公司是如何攻克这一难关的。在筛选阶段，UCB的所有结合片段都是以单臂Fab形式存在，这些Fab又分两种格式：Fab-Y和Fab-X。Fab-Y的C端带着一段多肽Y，而Fab-X的C端则带有可结合Y的scFv，两者混合后会形成一个临时的、可供筛选的Fab-KD-Fab双抗。Fab-KD-Fab技术的最大优势是节省了蛋白制备、纯化的成本。针对两种抗原A和B，UCB团队只需制备10种针对A的Fab-Y和10种针对B的Fab-X，一共20个蛋白，而不是100个蛋白。所有100种双抗都可以通过Fab-Y和Fab-X混合而生成。图片来源：参考资料148、UCB有一个项目是筛选抑制纤维化的双抗药物。人的肺（或肾）成纤维细胞与气管（或近端肾小管）上皮细胞混合培养，在培养液中加入不同的双抗分子，最后用免疫荧光方法比较各类蛋白纤维和细胞外基质的沉积程度。抑制纤维化可能的靶点有22个，双靶点的组合数就达到228种（理论上应该是231种可能：22 x 21 / 2）, 再考虑针对同一靶点有多种Fab，一共有2000个双抗需要被制备、筛选。而UCB采用Fab-KD-Fab技术，只需制备130种Fab分子作为起始原料就可以覆盖所有可能的双抗。图片来源：参考资料149、结果显示，一种双抗组合可以成功抑制细胞外基质的沉积或纤维化，而这种效果是两种单抗或其联合用药无法达到的。至此，UCB通过高通量筛选成功地找到一个抑制纤维化的候选双抗药物。其它公司也有自己的独特技术来构建大规模的双抗分子库，比如Genmab的DuoBody技术平台。10、一旦双靶点和双binder组合选定，下一步就要决定该双抗采取何种格式。双抗主要有三种格式：片段格式（左图），非对称的IgG类抗体格式（中图），和对称的IgG类抗体格式（右图）。每种格式里还有多种不同版本，图中给出的只是有代表性的例子。图片来源：Harpoontx.com/science/11、和IgG类双抗药相比，片段双抗主要有两个优势：由于其分子量小，它们可以更容易地渗透到肿瘤或靶向组织内，还可以结合到全长抗体不易接触的表位。但片段双抗的主要缺点是由于缺乏Fc，它们不能结合FcRn受体，因此体内半衰期短。比如Blincyto采取的是BiTE格式（左图），在体内的半衰期只有4个小时，其每个治疗周期需要连续28天静脉输液，给患者带来极大的不便，也增加了治疗费用。片段双抗可以通过改造而克服这一缺点。比如，Harpoon Therapeutics的TriTAC技术在片段双抗之间再加上能结合白蛋白（HSA）的抗体片段（右图）。片段双抗也可以和Fc融合而延长半衰期。图片来源：参考资料1812. 截至2019年6月份的数据表明，已进入或即将进入临床阶段的双抗药物中，非对称的IgG类双抗药占大部分——约60%。非对称IgG类双抗药的最大局限性是其生产过程中的效率问题。13、一个单克隆抗体是由两个相同的重链和两个相同的轻链构成。轻链与重链之间、重链与重链之间通过二硫键联结。在生产单抗蛋白时，先需要将两种质粒转染进同一个细胞（CHO或HEK293）里。一个质粒携带重链基因，另一个携带轻链基因。细胞同时表达重链蛋白和轻链蛋白，两种蛋白再自动组装成一个抗体分子，被细胞分泌到培养液里，不会有相似的副产物。但用细胞表达双抗分子时，事情就变得复杂一些。一个非对称IgG类双抗分子包含4个不同的蛋白链。宿主细胞需要被转染4种质粒，分泌出的抗体蛋白并不是100%想要的双抗。14、在细胞内，轻链与重链之间，重链与重链之间会随机配对。最后组装出的抗体分子会出现16种可能，10种蛋白分子。假设每种配对的概率都相同（实际上概率有些差异），我们所需要的双抗蛋白分子（红圈标出的）只占所有产物的1/8或12.5%。这不但导致了低效率的生产流程，而且还使提纯过程变得异常复杂：双抗很难从其它相似的抗体产物中分离出来。15、为了解决错配问题，工业界已经开发出很多创新技术。解决重链错配的常见技术有Genentech发明的Knobs-into-holes（KiH），Novimmune发明的Common Heavy Chain策略，和Regeneron发明的Fc双突变技术。KiH技术是在两种重链上引入不同的突变，使得同种重链无法配对，而异种重链则榫卯相扣。Common Heavy Chain策略则是使用同一个重链，对不同抗原的特异性主要由不同的轻链决定。Fc双突变技术与前两个技术不同。它不会导致单一配对，但便于选择性地提纯。一个重链还是野生型，另一个重链则引入两个突变（H435R和Y436F）。杂合重链双聚体与蛋白A的结合力比纯和突变重链双聚体高，但比纯和野生重链双聚体低。这样在蛋白提纯的过程中可以选择性地把含有杂合重链双聚体的双抗分子纯化出来。图片来源：参考资料1716、解决重轻链错配的常见技术有Common Light Chain策略，罗氏开发的CrossMab技术，Merck KGaA开发的CH1: CL界面改造技术，和药明生物、Invenra等公司开发的CH1: CL置换技术。Common Light Chain策略是使用同一个轻链，对不同抗原的特异性主要由不同的重链可变区决定。CrossMab技术（之一）是将一侧的轻重链的CH1和CL互相调换，这样野生的重链只能和野生的轻链配对，而含CL域的重链只能和含CH1的轻链配对。在CH1: CL界面改造技术中，一侧的CH1和CL各引入一系列突变，使得改造后的重、轻链依然能结合，但和野生型的轻、重链相排斥。药明生物的WuXiBody技术是通过将其中一对轻、重链的CH1/CL结构域置换为TCR Cα / Cβ而实现；与此相似，Invenra的B-body技术是将其中一对轻、重链的CH1/CL结构域置换为一对儿其它抗体结构域（未披露具体信息）。图片来源：参考资料13和1817、现在处于临床阶段的双抗候选药的85%是用来治疗肿瘤的，而抗肿瘤双抗药的大部分是T细胞导向双抗（T-cell redirecting bispecific antibodies, 简称TRBA），即有CD3结合臂的双抗。在剩下的篇幅中，让我们来重点讨论一下TRBA。图片来源：参考资料1118、T细胞表面的CD3和TCR组成CD3-TCR复合体，用来结合抗原呈递细胞（APC）表面的MHC-抗原片段。TRBA则绕开了MHC的限制，激活T细胞，把T细胞的火力引向了肿瘤细胞。TRBA的一个结合臂靶向肿瘤细胞表面的抗原（TAA），另一个结合臂结合T细胞表面的CD3ε，起到CD3ε激动剂的作用。TAA-TRBA-CD3-TCR形成了类似于MHC-peptide-TCR-CD3的免疫突触（IS），T细胞被激活，释放颗粒酶、穿孔素等蛋白，从而引起肿瘤细胞的裂解。图片来源：参考资料2419、正如前文所言，处于临床阶段的TRBA候选药物有很多种。Genentech的Mosunetuzumab就是其中之一。Mosunetuzumab是一个靶向B细胞表面的CD20的非对称全长双抗。它的Fc部分引进了一个突变（N297G）, 去除了ADCC作用，以避免误伤T细胞。图片来源：www.biooncology.com/pipeline-molecules/cd20-tcb.html; 参考资料920、罗氏正在开发的Glofitamab（CD20-TCB或RG6026）是另一个TRBA例子。Glofitamab的独特之处在于它与CD20的结合是二价的，与CD3是单价的。这种格式增强了它杀死肿瘤细胞的能力。另外，它的Fc部分只保留了FcRn结合位点，但不会引起免疫效应，从而既保留了长的生物半衰期又不会误伤T细胞。从Glofitamab的结构示意图（右上角）可以看出，为了避免错配，这个分子的设计至少采用了三个技术：KiH，CrossMab和CH1:CL电荷界面。图片来源：参考资料2421、 T细胞导向双抗经常被拿来和另一种合成免疫（synthetic immunity）治疗手段——CAR-T作比较。作为第二代TRBA的代表，Mosunetuzumab、CD20TCB和Regeneron的REGN1979在一期临床试验中显示了对B淋巴瘤的良好疗效，不亚于已上市的CAR-T疗法。有两点需要说明的是，Kymriah（Tisagenlecleucel）和Yescarta （Axicabtagene Ciloleucel）的靶向抗原是CD19，而这三个TRBA靶向CD20。另外，TRBA和CAR-T之间还从没做有过头对头的临床试验比较。根据表中的数据作横向比较还需谨慎。ORR为客观应答率，CR为完全缓解率。图片来源：参考资料2422、CAR-T最常见的副作用是细胞因子风暴（CRS）和神经毒性。和已上市的CAR-T疗法相比，三个TRBA的这两项副作用的发生频率和严重程度都有降低。图片来源：参考资料1223、尽管如此，TRBA在药效和安全性上还有很大的提高空间。提高药效大致可以从7个方面下手：（A）T细胞结合臂靶向的受体不仅仅局限于CD3（由黄色的椭圆代表），还可以从CD28，CD2和αβTCR中选择；（B）T细胞结合臂可以靶向CD3的不同表位；（C）TRBA可以采取多种格式，包括片段双抗和类IgG双抗；（D）癌细胞表面上的TAA密度也影响TRBA的效果；（E）形成的TAA-TRBA-CD3-TCR的空间尺度对癌细胞的杀伤力也有影响，而这是由TRBA的格式、TAA的大小、TAA上的结合表位与癌细胞膜之间的距离等因素决定的；（F）增加TRBA与TAA的亲和力会增加对癌细胞的杀伤力；（G）调整TRBA与CD3的亲和力可改变TRBA的药效和毒性。（G）比较复杂。一般来说，TRBA与CD3的亲和力（affinity）或总亲和力（avidity）不能太高，否则将导致TRBA和循环中的T细胞率先结合，不能有效渗入肿瘤，也产生很多副作用。图片来源：参考资料624、让我们先看一个通过（A）来提高对肿瘤细胞杀伤力的例子。激活T细胞并使之持续增殖、保持对肿瘤细胞的杀伤力需要两个信号：第一个信号是由CD3-TCR复合体介导的，引起细胞因子的分泌；第二个信号是由CD28介导的，抑制T细胞凋亡。设计TRBA时一般只考虑了第一个信号，因此TRBA经常引起T细胞无能化（anergy）而限制了T细胞的持久杀伤作用。但双信号这个概念已经被应用在第二代、第三代CAR-T的设计中：CAR的膜内部分既包括CD3ζ（信号1），又包括CD28的膜内激活域（信号2）。图片来源：参考资料2025、Sanofi设计的三特异性抗体就同时靶向这两个信号通路。这个三抗的一个结合臂靶向骨髓瘤细胞表面上的CD38，另一个结合臂同时靶向CD3和CD28。为了降低引起CRS的风险，这个分子被设计成与CD3ε的亲和力相对不高（KD ~ 20 nM，而anti-CD28和anti-CD38与各自靶点的KD分别为2 nM和4 nM）。在细胞和动物实验中，CD38 / CD3 x CD28三抗显示了对肿瘤细胞的持久杀伤力。图片来源：参考资料2426、TRBA的主要副作用是CRS。有没有可能只保留TRBA对肿瘤细胞的裂解能力，但又剔除其引起CRS的风险？研究表明，细胞杀伤力和CRS都依赖于TCR刺激，但是它们需要不同强度的CD3结合水平。细胞毒性T细胞（CTL）有两种不同的激活阈值，引起细胞因子释放的CD3结合率阈值要比细胞裂解阈值高得多，至少相差百倍。因此，可以通过减弱其对T细胞的亲和力或增加其TAA / CD3结合价比例来设计更安全的TRBA。IGM Biosceinces设计的IGM2323就是这样一个例子。它由靶向CD20的IgM五聚体和一个靶向CD3的scFv构成。也就是说，IGM-2323对CD20和CD3的结合价之比为10：1。图片来源：参考资料2327、在细胞实验中，IgM版本的双抗比IgG版本显示了对肿瘤细胞的更强的杀伤力。图片来源：参考资料2328. 而同时在细胞和动物（包括猴子）实验中，和IgG版本双抗相比，IGM-2323几乎不引起细胞因子的释放。IGM-2323正在一期临床试验中被评估。图片来源：参考资料1729、增加TRBA安全性的另一个办法是，让它只在肿瘤微环境（TME）中才被激活，才能招募T细胞。Maverick Therapeutics的COBRA技术平台就是建立在这一机理上。MVC-101是通过COBRA推出的一个三抗候选药。它可以结合EGFR和HSA（延长生物半衰期），但只能有条件地结合CD3。在其它组织中，它结合CD3的VH和VL分别被VLi和VHi所屏蔽，不能结合CD3。肿瘤及其周边中富含MMP2和MMP9等基质金属蛋白酶。在MMP的作用下，分子内的衔接链被剪断，含VLi、VHi和anti-HSA的一半蛋白分子被释放。剩下的半个分子两两配对，形成了可四价结合EGFR、两价结合CD3的双聚体双抗。在取得了良好的细胞和动物数据后，MVC-101即将进入临床试验。图片来源：www.affimed.com/rock-platform/innate-cell-engagers/; 参考资料2630、招募T细胞不是桥接双抗的唯一策略。Affimed公司通过ROCK技术推出了一系列招募NK细胞的候选双抗药。ROCK双抗既可以结合肿瘤细胞表面的TAA，又可结合NK细胞表面的CD16A（即FcγRIIIa），通过激活先天免疫系统和ADCC来裂解肿瘤细胞。这种双抗既保留了杀伤肿瘤的药效，又降低了TRBA的CRS风险。Affimed的管线领头项目AFM13靶向CD30和T细胞淋巴瘤，目前正在二期临床试验中被评估。31、未来10年将是多特异性抗体药的爆发期。双抗药发展到今天，是几十年来学术界和工业界在概念上、技术上不断产生突破日积月累的结果。几十家生物技术和制药公司都做出了重要贡献。我在这里仅列出文中涉及的公司。在不久的未来，双抗药将被广泛用来治愈顽疾，拯救生命。到那时，我们不应忘记，它们的背后是一系列的创新和众多的开拓者。参考资料：（上下滑动查看更多）1. Overington, J. P., Al-Lazikani, B. & Hopkins, A. L. (2006) How many drug targets are there?, Nature reviews Drug discovery. 5, 993-6.2. Krah, S., Kolmar, H., Becker, S. & Zielonka, S. (2018) Engineering IgG-Like Bispecific Antibodies-An Overview, Antibodies (Basel). 7.3. Santos, R., Ursu, O., Gaulton, A., Bento, A. P., Donadi, R. S., Bologa, C. G., Karlsson, A., Al-Lazikani, B., Hersey, A., Oprea, T. I. & Overington, J. P. (2017) A comprehensive map of molecular drug targets, Nature reviews Drug discovery. 16, 19-34.4. Tustian, A. D., Endicott, C., Adams, B., Mattila, J. & Bak, H. (2016) Development of purification processes for fully human bispecific antibodies based upon modification of protein A binding avidity, MAbs. 8, 828-38.5. Klein, C., Schaefer, W., Regula, J. T., Dumontet, C., Brinkmann, U., Bacac, M. & Umana, P. (2019) Engineering therapeutic bispecific antibodies using CrossMab technology, Methods. 154, 21-31.6. Weinkove, R., George, P., Dasyam, N. & McLellan, A. D. (2019) Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations, Clin Transl Immunology. 8, e1049.7. De Nardis, C., Hendriks, L. J. A., Poirier, E., Arvinte, T., Gros, P., Bakker, A. B. H. & de Kruif, J. (2017) A new approach for generating bispecific antibodies based on a common light chain format and the stable architecture of human immunoglobulin G1, J Biol Chem. 292, 14706-14717.8. Fischer, N., Elson, G., Magistrelli, G., Dheilly, E., Fouque, N., Laurendon, A., Gueneau, F., Ravn, U., Depoisier, J. F., Moine, V., Raimondi, S., Malinge, P., Di Grazia, L., Rousseau, F., Poitevin, Y., Calloud, S., Cayatte, P. A., Alcoz, M., Pontini, G., Fagete, S., Broyer, L., Corbier, M., Schrag, D., Didelot, G., Bosson, N., Costes, N., Cons, L., Buatois, V., Johnson, Z., Ferlin, W., Masternak, K. & Kosco-Vilbois, M. (2015) Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG, Nat Commun. 6, 6113.9. Bacac, M., Colombetti, S., Herter, S., Sam, J., Perro, M., Chen, S., Bianchi, R., Richard, M., Schoenle, A., Nicolini, V., Diggelmann, S., Limani, F., Schlenker, R., Husser, T., Richter, W., Bray-French, K., Hinton, H., Giusti, A. M., Freimoser-Grundschober, A., Lariviere, L., Neumann, C., Klein, C. & Umana, P. (2018) CD20-TCB with Obinutuzumab Pretreatment as Next-Generation Treatment of Hematologic Malignancies, Clin Cancer Res. 24, 4785-4797.10. Strohl, W. R. & Naso, M. (2019) Bispecific T-Cell Redirection versus Chimeric Antigen Receptor (CAR)-T Cells as Approaches to Kill Cancer Cells, Antibodies (Basel). 8.11. Zhukovsky, E. A., Morse, R. J. & Maus, M. V. (2016) Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection, Curr Opin Immunol. 40, 24-35.12. Ellerman, D. (2019) Bispecific T-cell engagers: Towards understanding variables influencing the in vitro potency and tumor selectivity and their modulation to enhance their efficacy and safety, Methods. 154, 102-117.13. Labrijn, A. F. (2019) Bispecific Antibodies: New Strategies and Case Studies in Antibody Engineering & Therapeutics 2019 San Diego, CA.14. Finney, H. M. (2019) Bispecific Target Discovery by Screenign a Large "Select, Mix & Assay" Combinatorial Library in Antibody Engineering & Therapeutics 2019 San Diego, CA.15. Joshi, K. (2019) Toward a Deeper Understanding of Bispecific Antibodies in Antibody Engineering & Therapeutics 2019 San Diego, CA.16. Wang, Q., Chen, Y., Park, J., Liu, X., Hu, Y., Wang, T., McFarland, K. & Betenbaugh, M. J. (2019) Design and Production of Bispecific Antibodies, Antibodies (Basel). 8.17. Zhu, Y., Shen, R., Hao, R., Wang, S. & Ho, M. (2020) Highlights of Antibody Engineering & Therapeutics 2019 in San Diego, USA: Bispecific Antibody Design and Clinical Applications, Antibody Therapeutics.18. Labrijn, A. F., Janmaat, M. L., Reichert, J. M. & Parren, P. (2019) Bispecific antibodies: a mechanistic review of the pipeline, Nature reviews Drug discovery. 18, 585-608.19. Bonisch, M., Sellmann, C., Maresch, D., Halbig, C., Becker, S., Toleikis, L., Hock, B. & Ruker, F. (2017) Novel CH1:CL interfaces that enhance correct light chain pairing in heterodimeric bispecific antibodies, Protein Eng Des Sel. 30, 685-696.20. Garfall, A. L. & June, C. H. (2019) Trispecific antibodies offer a third way forward for anticancer immunotherapy, Nature. 575, 450-451.21. Wu, L., Seung, E., Xu, L., Rao, E., Lord, D. M., Wei, R. R., Cortez-Retamozo, V., Ospina, B., Posternak, V., Ulinski, G., Piepenhagen, P., Francesconi, E., El-Murr, N., Beil, C., Kirby, P., Li, A., Fretland, J., Vicente, R., Deng, G., Dabdoubi, T., Cameron, B., Bertrand, T., Ferrari, P., Pouzieux, S., Lemoine, C., Prades, C., Park, A., Qiu, H., Song, Z., Zhang, B., Sun, F., Chiron, M., Rao, S., Radošević, K., Yang, Z.-y. & Nabel, G. J. (2020) Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation, Nature Cancer. 1, 86-98.22. Nabel, G. (2019) Trispecific Antibodies for Treating Cancer and AIDS in Antibody Engineering & Therapeutics 2019 San Diego, CA.23. Chen, D. S. (2019) Defining the Light at the End of the Tunnel: Biologic Problems and Engineering Solutions in Cancer Immunotherapy in Antibody Engineering & Therapeutics 2019 San Diego, CA.24. Budde, E. (2019) Clinical Use of Bispecific Antibodies in Treating B Cell Lymphoma in Antibody Engineering & Therapeutics 2019 San Diego, CA.25. Tesar, M. (2019) CD16A, NK Cell Targeting in Antibody Engineering & Therapeutics 2019 San Diego, CA.26. Haneke, T., Rajkovic, E., Treder, M., Tesar, M. & Koch, J. (2019) Redirected Optimized Cell Killing (ROCK®): A novel multispecific antibody platform for innate immune cell engagement to fight cancer in NK2019 Luxembourg.

细胞疗法

2025-06-12

·ioncology

2025 ACML丨王三斌&许景艳教授：从突破到精准，免疫治疗前移趋势引领亚太淋巴瘤诊疗新生态

点击蓝字关注我们前言：2025年5月31日至6月1日，由罗氏制药主办的首届亚太地区恶性淋巴瘤会议（APAC congress on malignant lymphoma，ACML）在上海市隆重召开。本次会议聚焦于淋巴瘤领域的前沿进展及热点话题，致力于推动亚太地区在淋巴瘤研究与治疗方面的学术协作与交流，为提升区域淋巴瘤诊疗水平搭建了重要平台。会议期间，中国人民解放军联勤保障部队第920医院王三斌教授、南京鼓楼医院许景艳教授，与基因泰克转化医学部杰出科学家Yanwen Jiang博士及罗氏制药中国血液领域负责人洪晓女士，围绕淋巴瘤诊疗热点议题分享了极具价值的临床洞见。《肿瘤瞭望-血液时讯》特提炼核心内容，以飨读者。挑战尚存疗效天花板亟待打破，特殊人群需求远未满足ACML指南针“提升治愈率、优化治疗耐受性及长期生存获益已成为当下淋巴瘤研究领域的重要方向。”迄今为止，尽管全球淋巴瘤诊疗技术已取得长足进步，但临床实践中的多重桎梏仍制约着患者生存获益的进一步提升。本次ACML会议深度聚焦该领域前沿进展，系统性地提出了治疗策略的革新方向与临床实践的优化路径。会议期间，王三斌教授与许景艳教授通过多维度剖析，揭示了当前治疗格局中亟待突破的两大痛点——疗效“天花板”亟待打破，特殊人群需求远未满足。许景艳教授结合南京鼓楼医院诊疗数据指出：“在原发性中枢神经系统淋巴瘤（PCNSL）患者中，传统甲氨蝶呤为基础的化疗方案五年生存率不尽如人意，且高龄（特别是≥80岁）、肾功能不全等特殊患者，常因药物毒性问题丧失标准治疗机会”。这种治疗可行性与疗效保障的双重缺失，体现了领域治疗范式革新之迫切。王三斌教授进一步强调：“尽管经典R-CHOP方案（利妥昔单抗+环磷酰胺+长春新碱+多柔比星+泼尼松）在淋巴瘤治疗中具有里程碑意义，但临床上仍有众多患者面临难治及复发困境。此外，老年侵袭性淋巴瘤患者常因器官功能储备不足或合并基础疾病，难以耐受标准剂量化疗。针对复发难治性淋巴瘤患者，尤其是中枢神经系统受累者，疗效与生存亟待改善。这些未解难题，共同构成了制约当前淋巴瘤治疗领域整体生存率提升的关键障碍，故而提升治愈率、优化治疗耐受性及长期生存获益已成为当下研究的重要方向”。因此，在分子生物学机制解析不断深入的背景下，凭借精准诊疗技术优化疗效，同时构建覆盖特殊人群的个体化治疗体系，将成为淋巴瘤从"可控制疾病"迈向"可治愈疾病"的核心突破口。破局之策Pola-R-CHP实现生存突破，CD20/CD3双特异性抗体疗效优异ACML指南针“Pola-R-CHP方案显著提升了DLBCL患者的五年无进展生存率，具有持续生存获益优势，为初治患者带来了实质性的疗效改善。”“格菲妥单抗可在透过血脑屏障后，凭借免疫激活功能，有效活化和招募T细胞，发挥精准抗肿瘤效应，有望进一步提升颅内病灶控制率。”“莫妥珠单抗4年长期随访数据显示，滤泡性淋巴瘤患者的ORR接近80%，彰显了其持久、深度缓解的优异疗效。”近年来，众多突破性创新免疫药物的出现为破解领域困局注入了强劲动力。首先，王三斌教授高度评价了抗体药物偶联物（ADC）维泊妥珠单抗（Polatuzumab，Pola）的价值：“作为二十年来首个经全球III期POLARIX研究证实1，疗效优于R-CHOP的创新药物，维泊妥珠单抗实现了弥漫大B细胞淋巴瘤（DLBCL）一线治疗的里程碑式飞跃。”许景艳教授进一步补充了该研究五年随访数据——在DLBCL总体意向性治疗（ITT）人群中，相较于经典R-CHOP方案，Pola-R-CHP方案显著提升了五年无进展生存率（64.2% vs. 59.1%，HR=0.77）2，证实其持续生存获益优势，为初治患者带来了实质性的疗效改善。在复发难治领域及特殊亚型中，双特异性抗体则展现出强大的应用潜力与前景。王三斌教授强调：“侵袭性淋巴瘤领域治疗模式已从传统化疗主导逐步转向靶免治疗协同应用。尽管化疗仍是当前治疗框架的基石，但以格菲妥单抗（Glofitamab）为代表的双抗药物和维泊妥珠单抗已广泛渗透至临床实践，显著改善了患者预后。同时，联合CD20/CD3双特异性抗体的策略正逐步在中枢神经系统淋巴瘤中展现增效潜力。研究显示格菲妥单抗可在透过血脑屏障后，凭借免疫激活功能，有效活化和招募T细胞，发挥精准抗肿瘤效应3，有望进一步提升颅内病灶控制率。”许景艳教授特别指出：“以格菲妥单抗为核心的新型方案，为高龄及不耐受传统化疗的患者提供了全新的治疗希望。未来，临床实践需进一步探索其在联用方案中的最佳模式及精准用药策略，以期实现个体化治疗效益最大化。”同时，针对惰性淋巴瘤领域，许景艳教授分享了CD20/CD3双抗莫妥珠单抗（Mosunetuzumab）GO29781研究的4年长期随访数据——总体滤泡性淋巴瘤患者的客观缓解率（ORR）接近80%4，彰显了其持久、深度缓解的优异疗效。目前，莫妥珠单抗已获批单药用于治疗既往接受过至少两线系统性治疗的复发或难治性滤泡性淋巴瘤成人患者，其高应答率和固定治疗时间模式不仅可能改变领域格局，更为其向一线治疗前移及联合方案探索奠定了循证基础。进无止境格菲妥单抗获批二线，莫妥珠单抗一线研究备受期待ACML指南针“基于格菲妥单抗、莫妥珠单抗等新型免疫治疗药物的卓越疗效，各界正加速推动其适应症‘前移’——从后线走向一/二线治疗。”随着免疫治疗的突破性进展与优质药物的相继出现，淋巴瘤治疗策略趋势逐渐转向免疫治疗线序前移与新型联合方案的系统性探索。许景艳教授清晰阐述了这一演化方向：“基于格菲妥单抗、莫妥珠单抗等新型免疫治疗药物的卓越疗效，各界正加速推动其适应症‘前移’——从后线走向一/二线治疗。”这一趋势在滤泡性淋巴瘤等惰性亚型中尤为显著，特别是莫妥珠单抗的一线研究备受期待；在侵袭性淋巴瘤领域，格菲妥单抗近期凭借明确的生存获益数据，已在国内获批用于复发或难治性弥漫大B细胞淋巴瘤患者的二线治疗，并有望继续向一线治疗适应症拓展。在治疗选择丰富化的背景下，精准风险分层与个体化方案优化同样成为提升临床获益的关键。王三斌教授强调：“未来，突破需聚焦给药方案优化、生物标志物驱动的精准分层及创新联合策略探索。”许景艳教授则在分享中国经验时提及，南京鼓楼医院在胃黏膜相关淋巴组织（MALT）淋巴瘤中，已形成涵盖抗幽门螺杆菌（HP）治疗的标准路径；而对于非胃边缘区淋巴瘤等高肿瘤负荷的惰性淋巴瘤患者，院内正积极探索奥妥珠单抗联合方案等创新策略。针对老年、脆弱及合并脏器功能障碍的患者，“靶免药物的免化疗（chemo-free）方案的开发及与传统疗法的协同应用，正成为提供有效且耐受性更佳疾病控制的重要策略。”综上，免疫治疗线序前移与创新联合方案的探索趋势，有望推动淋巴瘤临床实践向"更有效、更安全、更个体化"的方向持续演进。共赢未来创新免疫药物疗效优势明确，助力优化亚太人群治疗方案ACML指南针“2025 EHA即将公布的POLARIX研究亚组数据，或将为维泊妥珠单抗的广泛应用提供依据，特别是在亚洲人群中可能展现出更显著的生存获益趋势，将为制定符合亚太患者特征的全程管理策略提供重要参照。”“维泊妥珠单抗等创新药物展现的明确疗效优势，可成为构建兼具临床价值与可及性解决方案的突破口。若亚太人群数据进一步验证其治疗优势，将极大推动该药物的标准化应用。"亚太地区淋巴瘤诊疗面临着独特的临床挑战，其人群遗传异质性、疾病谱系特征及医疗资源配置差异，要求构建契合区域特点的解决方案。两位专家在交流中均强调，基于亚洲人群的真实世界数据是优化治疗策略的核心基础。许景艳教授透露，2025欧洲血液学协会年会（EHA）即将公布的POLARIX研究亚组数据，或将为维泊妥珠单抗的广泛应用提供依据，特别是在亚洲人群中可能展现出更显著的生存获益趋势，将为制定符合亚太患者特征的全程管理策略提供重要参照。本次ACML期间汇报的韩国研究数据，亦从多维度验证了该药物的实践价值，凸显其在亚太临床场景中的广泛适用性。王三斌教授从区域协作视角提出战略构想，强调需建立"亚太特色"的诊疗创新生态：“在医疗资源分布不均衡及支付能力存在一定差异的现实背景下，维泊妥珠单抗等创新药物展现的明确疗效优势，可成为构建兼具临床价值与可及性解决方案的突破口。若亚太人群数据进一步验证其治疗优势，将极大推动该药物的标准化应用。"面向淋巴瘤诊疗的未来发展，深化创新药物应用推进个体化方案优化成为关键路径。两位教授一致肯定ACML在促进学术交流与转化研究中的平台价值。许景艳教授期待"依托格菲妥单抗、莫妥珠单抗等新型‘武器’取得的临床突破，开发针对亚太高发亚型及特殊人群的精准治疗路径。"王三斌教授则建议"未来，ACML应定位于前沿成果首发阵地与多中心协作网络枢纽，通过促进跨国药企、临床机构及基础研究团队的深度协同，聚焦未满足临床需求开展联合攻关，最终形成覆盖疾病全周期的精准诊疗体系。"两位专家的期许旨在推动科研成果高效转化为临床实践，为亚太乃至全球患者提供兼具可及性与效价比优势的创新治疗方案，最终实现患者生存预后与生活质量的同步改善。END参考文献：（上下滑动查看更多）1.Gilles Salles, et al; Five-Year Analysis of the POLARIX Study: Prolonged Follow-up Confirms Positive Impact of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) on Outcomes.2.Song Y, Tilly H, Rai S, et al. Polatuzumab vedotin in previously untreated DLBCL: an Asia subpopulation analysis from the phase 3 POLARIX trial. Blood. 2023 Apr 20;141(16):1971-1981.3.Dickinson MJ, et al. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma [J]. N Engl J Med, 2022, 387(24): 2220-31.4.Mazyar shadman E A. Mosunetuzumab Continues to Demonstrate Clinically Meaningful Outcomes in Patients with Relapsed and/or Refractory Follicular Lymphoma after ≥2 Prior Therapies Including Those with a History of POD24: 4-Year Follow-up of a Pivotal Phase II Study [J]. 2024ASH, 2024, 4407.（来源：《肿瘤瞭望–血液时讯》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床结果免疫疗法临床研究

2025-06-12

·sobi.com

Sobi share new clinical data across multiple hematologic diseases at EHA 2025

Sobi® (STO: SOBI) will present data at the 30th EHA (European Haematology Association) hybrid congress, in Milan, Italy (12-15 June). The congress will feature the latest advances in the treatment of diffuse large B-cell lymphoma (DLBCL), immune thrombocytopenia (ITP), myelofibrosis, paroxysmal nocturnal haemoglobinuria (PNH), and primary hemophagocytic lymphohistiocytosis (pHLH). An extensive programme of poster presentations will showcase Sobi’s commitment to helping patients with rare diseases by advancing treatment options. In addition, Sobi will host several scientific symposiums at the congress including: 1.Advancing Therapeutic Knowledge in Paroxysmal Nocturnal Haemoglobinuria: Reshaping disease management to unlock new norms, Thursday, 12 June, 10:00am - 11:30am CEST, at Amber Hall 3 & 4. 2. Boosting Platelets: Expert Approaches to Adult Immune Thrombocytopenia (ITP), Saturday 14 June, 8.00 am - 9.30 am CEST, at Amber Hall 7 & 8. 3. Dissecting Treatment Sequencing in relapsed/refractory DLBCL, from laboratory to real life. Saturday, 14 June, 8:00 am – 9:30 am, CEST at Coral Hall 1. “The breadth of data that we share at this year’s EHA congress demonstrates Sobi’s comprehensive approach to addressing rare conditions in haematology. We are proud to contribute to advancing the science in several indications from early clinical phases in diffuse large B-cell lymphoma to clinical and real-world evidence in myelofibrosis, primary hemophagocytic lymphohistiocytosis, immune thrombocytopenia and paroxysmal nocturnal haemoglobinuria,” said Lydia Abad-Franch, MD, Head of R&D and Medical Affairs, and Chief Medical Officer at Sobi. Key data to be presented at EHA 2025 DLBCL PS1911: Initial Results From LOTIS-7: A Phase 1b Study of Loncastuximab Tesirine Plus Glofitamab in Patients With Relapsed/Refractory (R/R) Diffuse Large BCell Lymphoma (DLBCL) Presenting Author: Juan Pablo Alderuccio Poster presentation Session title: Poster Session 2Session date: Saturday, 14 June Session time: 18:30-19:30 CEST Location: Poster Hall PS1957: Updated Safety Run-in Results from LOTIS-5: A Phase 3, Randomized Trial of Loncastuximab Tesirine with Rituximab Versus Immunochemotherapy in Patients With R/R DLBCL Presenting Author: Carmelo Carlo-Stella Immune Thrombocytopenia (ITP) PF1236: Platelet Response to Avatrombopag Among Patients with Primary Immune Thrombocytopenia Who Switched from Eltrombopag or Romiplostim: the REAL-AVA 2.0 Real-World Study Presenting Author: Shruti Chaturvedi Poster presentation Session title: Poster Session 1Session date: Friday, 13 June Session time: 18:30 - 19:30 CEST Location: Poster Hall PF1239: Durability of Response to Avatrombopag Among Patients with Primary Immune Thrombocytopenia: The REAL-AVA 2.0 Real-World Study Presenting Author: Srikanth Nagalla PF1251: Clinically Meaningful Response to Avatrombopag: A Phase 3B Trial for Treatment of Children with ITP Presenting Author: Rachael F. Grace PS2231: Effectiveness and safety of avatrombopag for the treatment of adults with newly diagnosed, persistent, or chronic immune thrombocytopenia: Interim results from the phase 4 ADOPT study Presenting Author: Waleed Ghanima Poster presentation Session title: Poster Session 2Session date: Saturday, 14 June Session time: 18:30 - 19:30 CEST Location: Poster Hall PS2234: Efficacy and safety of avatrombopag for the treatment of pediatric immune thrombocytopenia in the open-label extension of a phase 3, randomized, double-blind, placebo-controlled trial Presenting Author: Rachael F. Grace PS2239: Real-World Treatment Patterns & Clinical Outcomes in Thrombopoietin Receptor Agonist Naive Patients with Immune Thrombocytopenia Treated with Avatrombopag: Interim Results from the REAL-AVA 3.0 Study Presenting Author: Sandhya Panch PS2242: Effectiveness and safety of avatrombopag for treatment of immune thrombocytopenia in older patients and those with comorbidities or prior TPO-RA exposure: Interim results from the phase 4 ADOPT study Presenting Author: María Eva Mingot-Castellano PS2244: Response to Avatrombopag Among Patients with Chronic and Persistent Primary Immune Thrombocytopenia: the REAL-AVA 2.0 Real-World Study Presenting Author: M Y Levy PS2250: Evaluation of Efficacy and Safety of Avatrombopag in Children with Immune Thrombocytopenia based on Disease Duration: Results from the Avatrombopag Phase 3-b Pediatric Trial Presenting Author: Rachael F. Grace PB3676: Baseline Correlates with Durability of Avatrombopag Response: A Phase 3B Trial for Treatment of Children with ITP Publication Only Published on May 14 at 15:30 CEST PB3684: Consistent Response to Avatrombopag across Various Baseline Characteristics: Results from the Phase 3-b Trial for the Treatment of Children with Immune Thrombocytopenia Myelofibrosis PF849: Hematologic improvement experienced by pacritinib-treated patients with myelofibrosis in real-world clinical settings Presenting Author: Michael Marrone Poster presentation Session title: Poster Session 1Session date: Friday, 13 June Session time: 18:30 - 19:30 CEST Location: Poster Hall PF1242: Efficacy of pacritinib vs momelotinib in patients with thrombocytopenic MF: a matched adjusted indicated treatment comparison Presenting Author: Koo Wilson PF1306: Transfusion-related cost and time burden offsets in patients with myelofibrosis treated with pacritinib compared to best available therapy based on PERSIST-2 trial Presenting Author: Abiola Oladapo PS1827: Real-world effectiveness of pacritinib in patients with myelofibrosis who have concurrent thrombocytopenia and anemia Presenting Author: Raajit Rampal Poster presentation Session title: Poster Session 2 Session date: Saturday, 14 June Session time: 18:30-19:30 CEST Location: Poster Hall PS1842: Real-World Treatment Patterns and Clinical Outcomes in Patients with Myelofibrosis Treated with Pacritinib (PAC) with platelets ≥50 x109/L at PAC initiation: Interim results from the MY-PAC Study Presenting Author: Doug Tremblay PS2295: Economic Burden of Cytopenia in Patients with Myelofibrosis: Analysis of a US National Administrative Claims Database Presenting Author: Lucia Marasova PB3079: Cytopenia is associated with real-world disease progression and diminished survival in patients with myelofibrosis: Analysis of a US national administrative claims database Publication Only Published on May 14 at 15:30 CEST Paroxysmal Nocturnal Hemoglobinuria PF672: Early response in complement inhibitor naïve patients with paroxysmal nocturnal hemoglobinuria treated with pegcetacoplan in the Phase 3 PRINCE trial Presenting Author: Austin Kulasekararaj Poster presentation Session title: Poster Session 1Session date: Friday, 13 June Session time: 18:30 - 19:30 CEST Location: Poster Hall PF676: Interim analysis of the ongoing COMPLETE study on the real-world effectiveness of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria (PNH) Presenting Author: Regis Peffault de Latour PS1662: A benefit assessment of pegcetacoplan dose increase in the Phase 3 PEGASUS trial of PNH patients with difficult-to-control disease Presenting Author: Morag Griffin Poster presentation Session title: Poster Session 2Session date: Saturday, 14 June Session time: 18:30 - 19:30 CEST Location: Poster Hall PS1665: Benefit of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria irrespective of baseline transfusion status Presenting Author: Britta Höchsmann Primary Hemophagocytic Lymphohistiocytosis (pHLH) PF1036: Emapalumab in patients with primary hemophagocytic lymphohistiocytosis: Efficacy and safety outcomes from a multinational, open-label, single-arm study Presenting Author: Franco Locatelli Poster presentation Session title: Poster Session 1Session date: Friday, 13 June Session time: 18:30 - 19:30 CEST Location: Poster Hall About pegcetacoplan in rare diseases Pegcetacoplan is a targeted C3 therapy designed to regulate excessive activation of the complement cascade, a part of the body’s immune system, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is under investigation for rare diseases across haematology and nephrology. Pegcetacoplan is approved for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) as EMPAVELI®/Aspaveli® in the United States, European Union, and other countries globally About Doptelet® (avatrombopag) Doptelet® (avatrombopag) is indicated for the treatment of primary chronic immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments, and a treatment of severe thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo an invasive procedure. About Zynlonta® (loncastuximab tesirine)Zynlonta® (loncastuximab tesirine) is a CD19-directed antibody drug conjugate (ADC). Zynlonta as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy. About Sobi® Sobi is a global biopharma company unlocking the potential of breakthrough innovations, transforming everyday life for people living with rare diseases. Sobi has approximately 1,900 employees across Europe, North America, the Middle East, Asia and Australia. In 2024, revenue amounted to SEK 26 billion. Sobi’s share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com and LinkedIn. Contacts For details on how to contact the Sobi Investor Relations Team, please click here. For Sobi Media contacts, click here. We provide access to innovative treatments that transform life for people. Our therapies are concentrated within the areas of Haematology, Immunology and Specialty Care. We contribute to societies by improving access to treatment of rare diseases. Every day, we work actively to find better ways to understand and meet patient needs. Find out more about our business and financial performance. Here we present current and past media releases, images and videos.

临床3期免疫疗法临床结果上市批准临床1期

100 项与格菲妥单抗相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D11833	-	-	DB16371

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
复发性弥漫性大B细胞淋巴瘤	加拿大	Hoffmann-La Roche Ltd.	2023-03-25
难治性弥漫性大 B 细胞淋巴瘤	加拿大	Hoffmann-La Roche Ltd.	2023-03-25
弥漫性大B细胞淋巴瘤	加拿大	Hoffmann-La Roche Ltd.	2023-03-24
滤泡性淋巴瘤	加拿大	Hoffmann-La Roche Ltd.	2023-03-24
高级别B细胞淋巴瘤	加拿大	Hoffmann-La Roche Ltd.	2023-03-24
纵隔大b细胞淋巴瘤	加拿大	Hoffmann-La Roche Ltd.	2023-03-24

未上市

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
套细胞淋巴瘤	临床3期	韩国	罗氏（中国）投资有限公司	2023-10-09
套细胞淋巴瘤	临床3期	韩国	Genentech, Inc.	2023-10-09
套细胞淋巴瘤	临床3期	韩国	F. Hoffmann-La Roche Ltd.	2023-10-09
CD20阳性大B细胞淋巴瘤	临床3期	美国	Roche Holding AG	2023-09-18
CD20阳性大B细胞淋巴瘤	临床3期	中国	Roche Holding AG	2023-09-18
CD20阳性大B细胞淋巴瘤	临床3期	日本	Roche Holding AG	2023-09-18
CD20阳性大B细胞淋巴瘤	临床3期	阿根廷	Roche Holding AG	2023-09-18
CD20阳性大B细胞淋巴瘤	临床3期	澳大利亚	Roche Holding AG	2023-09-18
CD20阳性大B细胞淋巴瘤	临床3期	比利时	Roche Holding AG	2023-09-18
CD20阳性大B细胞淋巴瘤	临床3期	巴西	Roche Holding AG	2023-09-18

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


NCT04408638 (STARGLO, ASCO2025)	临床3期	弥漫性大B细胞淋巴瘤 CD20 \| CD3	274	Glofitamab (Glofit-GemOx)	鏇醖餘遞廠糧網膚醖醖(願願糧築構簾築壓鹽鹹) = 顧鬱製鬱鏇繭鹽衊壓膚淵壓遞壓廠齋鏇鹽齋糧 (選顧簾構艱齋顧膚膚鬱 ) 更多	积极	2025-05-30
				Glofitamab (R-GemOx)	鏇醖餘遞廠糧網膚醖醖(願願糧築構簾築壓鹽鹹) = 構觸餘鏇齋顧壓構壓餘淵壓遞壓廠齋鏇鹽齋糧 (選顧簾構艱齋顧膚膚鬱 ) 更多
NCT04408638 (STARGLO, BusinessWire) 人工标引	临床3期	弥漫性大B细胞淋巴瘤	-	Columvi plus gemcitabine and oxaliplatin (GemOx)	網範積膚鹽網襯獵構壓(選構獵積淵構構衊醖鹽) = 醖鬱鏇淵網範餘製夢艱憲築壓觸夢繭簾遞鏇鏇 (遞憲蓋壓窪襯窪獵鹹繭 ) 达到	积极	2025-05-20
				Rituxan plus gemcitabine and oxaliplatin (GemOx)	網範積膚鹽網襯獵構壓(選構獵積淵構構衊醖鹽) = 齋襯糧糧廠鹹衊顧築鏇憲築壓觸夢繭簾遞鏇鏇 (遞憲蓋壓窪襯窪獵鹹繭 ) 达到
NCT04970901 (LOTIS-7, PipelineReview) 人工标引	临床1期	弥漫性大B细胞淋巴瘤二线 \| 三线	29	ZYNLONTA + glofitamab (2L+ DLBCL)	築衊鬱蓋築獵壓築齋餘(廠獵蓋鬱製鬱淵窪簾壓) = 鏇壓積襯構糧廠構鹹齋遞獵網構壓襯構醖築淵 (製遞鏇鹹簾簾簾網範繭 ) 更多	积极	2024-12-11
				ZYNLONTA (3L+ DLBCL)	築衊鬱蓋築獵壓築齋餘(廠獵蓋鬱製鬱淵窪簾壓) = 鏇遞齋襯膚簾齋築積獵遞獵網構壓襯構醖築淵 (製遞鏇鹹簾簾簾網範繭 ) 更多
NCT03075696 (ASH2024) 人工标引	临床2期	大B细胞淋巴瘤三线	155	Glofitamab	遞簾壓夢壓窪鬱衊糧網(獵醖鑰積餘壓襯遞襯齋) = two new Grade ≥3 AEs (neutropenia [Grade 3] and adenocarcinoma pancreas [Grade 4]) were reported. 遞顧鏇獵繭獵衊觸夢製 (鬱醖遞鹹淵鹽醖夢製製 )	积极	2024-12-09
NCT05364424 (GO43693, ASH2024) 人工标引	临床1期	弥漫性大B细胞淋巴瘤	41	Glofitamab inIfosfamideon CarboplatinEtoposide	糧醖鹹鬱廠窪積顧醖糧(淵積網範顧觸鹽鹽觸觸) = 獵鏇繭網窪構顧構獵夢獵積製壓願獵遞淵夢鹹 (醖構範廠鑰鹽淵衊繭憲, 60.0 ~ 90.7) 更多	积极	2024-12-09
ASH2024	N/A	难治性高级别 B 细胞淋巴瘤	-	Glofitamab+Polatuzumab Vedotin	襯膚艱遞網鏇積淵襯糧(築築壓鑰淵餘壓廠獵憲) = The most common adverse event (AE) was CRS (43%), which was mostly Grade (Gr) 1-2 (Gr 1 27%, Gr 2 15% per ASTCT criteria); one pt had Gr 3 CRS and one had fatal Gr 5 CRS (occurred in the context of unresolved infection; pt declined further CRS management at Gr 3). CRS events were managed with tocilizumab (34%), fluids (23%), low flow oxygen (20%), or corticosteroids (14%) and 3 pts (5.4%) were admitted to intensive care. 廠獵齋顧積糧鹽憲襯網 (膚構衊壓艱艱繭糧構網 ) 更多	-	2024-12-09
ASH2024	N/A	弥漫性大B细胞淋巴瘤	-	Glofit-GemOx	築繭觸築鹹選鹽廠淵廠(憲觸蓋廠鹽鏇構鹹顧齋) = 繭衊齋夢膚網鹹鹽襯鏇壓膚醖襯艱夢鏇顧壓築 (製衊網鏇窪艱簾鹹鹽艱 ) 更多	-	2024-12-09
				R-GemOx	築繭觸築鹹選鹽廠淵廠(憲觸蓋廠鹽鏇構鹹顧齋) = 蓋築襯餘鑰選餘遞蓋醖壓膚醖襯艱夢鏇顧壓築 (製衊網鏇窪艱簾鹹鹽艱 ) 更多
ASH2024	N/A	复发性弥漫性大B细胞淋巴瘤	-	Glofitamab Monotherapy	壓憲選積範襯鏇醖衊淵(鹽鏇蓋鹽憲顧窪襯淵範) = 憲壓構積膚糧艱鏇構鑰簾獵醖網範鹽構淵顧壓 (襯積鹹窪壓鹽觸蓋鬱鹹 ) 更多	-	2024-12-09
ASH2024	N/A	弥漫性大B细胞淋巴瘤	-	Glofitamab with Gemcitabine and Oxaliplatin	廠獵壓遞襯鑰醖鏇醖選(願衊選鬱簾夢鏇鹹鏇膚) = 選鹽淵築鹹襯選糧鬱鹽願遞簾觸製鏇鏇簾衊觸 (選顧觸網壓鹹鬱簾遞顧, NA) 更多	-	2024-12-09
				Rituximab with Gemcitabine and Oxaliplatin	廠獵壓遞襯鑰醖鏇醖選(願衊選鬱簾夢鏇鹹鏇膚) = 艱襯糧淵壓製繭築構築願遞簾觸製鏇鏇簾衊觸 (選顧觸網壓鹹鬱簾遞顧, NA) 更多
ASH2024	N/A	-	-	Vehicle control	獵夢衊鑰觸淵衊窪鏇網(醖積顧製餘膚選廠鏇遞) = 衊衊淵製淵膚簾膚膚窪餘鹹襯廠鑰窪繭鬱壓齋 (齋選積觸觸淵窪蓋構積 )	-	2024-12-08