This phase II trial tests the effectiveness of odronextamab given before chimeric antigen receptor T (CAR-T) cell therapy (bridging therapy) in patients with large B-cell lymphomas that have come back after a period of improvement (relapsed) or that have not responded to previous treatment (refractory). Odronextamab is a bispecific antibody that can bind to two different antigens at the same time. Odronextamab binds to CD3, a T-cell surface antigen, and CD20 (a tumor-associated antigen that is expressed on B-cells during most stages of B-cell development and is often overexpressed in B-cell cancers) and may interfere with the ability of cancer cells to grow and spread. Bridging therapy has been used to maintain disease control and to increase the chance of successful receipt of CAR-T cell therapy. However, bridging therapy is typically given after leukapheresis, which does not help prevent disease progression between the decision for CAR-T cell therapy and leukapheresis. Giving odronextamab as bridging therapy before leukapheresis may delay disease progression to allow leukapheresis and increase the likelihood of successful CAR-T cell therapy in patients with relapsed or refractory large B-cell lymphomas.

开始日期2025-10-15

申办/合作机构

University of Washington

[+1]

NCT07128641

/ Not yet recruiting临床2期IIT

A Phase II Study of Odronextamab in Treatment Naïve Patients With Low Tumor Volume Advanced Stage Follicular Lymphoma

The purpose of this study is to evaluate the safety and effectiveness of treating previously untreated Follicular Lymphoma (FL) with odronextamab.
The name of the study drug in this research study is:
-Odronextamab (a type of monoclonal antibody)

开始日期2025-10-01

申办/合作机构

Beth Israel Deaconess Medical Center, Inc.

[+1]

NCT06735664

/ 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]

100 项与奥德罗奈昔单抗相关的临床结果

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100 项与奥德罗奈昔单抗相关的转化医学

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100 项与奥德罗奈昔单抗相关的专利（医药）

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项与奥德罗奈昔单抗相关的文献（医药）

2025-12-31·mAbs

Antibodies to watch in 2025

Review

作者: Kapoor, Vaishali ; Kaplon, Hélène ; Crescioli, Silvia ; Visweswaraiah, Jyothsna ; Reichert, Janice M. ; Wang, Lin

The commercial development of antibody therapeutics is a global enterprise involving thousands of biopharmaceutical firms and supporting service organizations. To date, their combined efforts have resulted in over 200 marketed antibody therapeutics and a pipeline of nearly 1,400 investigational product candidates that are undergoing evaluation in clinical studies as treatments for a wide variety of diseases. Here, we discuss key events in antibody therapeutics development that occurred during 2024 and forecast key events related to the late-stage clinical pipeline that may occur in 2025. In particular, we report on 21 antibody therapeutics granted a first approval in at least one country or region during 2024, including bispecific antibodies tarlatamab (IMDELLTRA®), zanidatamab (Ziihera®), zenocutuzumab (BIZENGRI®), odronextamab (Ordspono®), ivonescimab (®), and antibody-drug conjugate (ADC) sacituzumab tirumotecan (®). We also discuss 30 investigational antibody therapeutics for which marketing applications were undergoing review by at least one regulatory agency, as of our last update on December 9, 2024, including ADCs datopotamab deruxtecan, telisotuzumab vedotin, patritumab deruxtecan, trastuzumab botidotin, becotatug vedotin, and trastuzumab rezetecan. Of 178 antibody therapeutics we include in the late-stage pipeline, we summarize key data for 18 for which marketing applications may be submitted by the end of 2025, such as bi- or multispecific antibodies denecimig, sonelokimab, erfonrilimab, and anbenitamab. Key trends in the development and approval of antibody formats such as bispecifics and ADCs, as well as clinical-phase transition and global approval success rates for these antibody formats, are reported.

2025-08-10·JOURNAL OF CLINICAL ONCOLOGY

Glofitamab Combined With Pola-R-CHP or R-CHOP as First Therapy in Younger Patients With High-Risk Large B-Cell Lymphoma: Results From the COALITION Study

Article

作者: Neeson, Paul ; Bennett, Rory ; Hunter, Sally M. ; Blombery, Piers ; Butler, Jason ; Hamad, Nada ; Harrop, Sean ; Minson, Adrian ; Yannakou, Costas K. ; Swain, Fiona ; Seymour, John F. ; Verner, Emma ; Janowski, Wojt ; Giri, Pratyush ; Ratnasingam, Sumita ; Herbert, Kirsten ; Lau, Lei Shong ; Wong, Shu Min ; Ku, Matthew ; Hertzberg, Mark ; Steiner, Thiago M. ; Dickinson, Michael J. ; Cheah, Chan Y. ; Saghebi, Javad ; Robertson, Molly ; Xie, Jing

PURPOSE:

Improved outcomes are needed for patients with high-risk (HR) large B-cell lymphoma (LBCL) who have <50% chance of cure with first-line (1L) R-CHOP chemotherapy. Patients with high burden or rapid progression are often excluded from 1L trials due to screening requirements. We report the investigator-initiated, phase II COALITION trial of the CD20xCD3 bispecific antibody glofitamab combined with R-CHOP or Pola-R-CHP in younger patients with HR features, designed to minimize time between diagnosis and treatment.

METHODS:

Patients age ≤65 years with LBCL and at least one HR feature (international prognostic index [IPI] ≥3, National Comprehensive Cancer Network-IPI ≥4, or rearrangements of MYC and BCL2 and/or BCL6 ) received one cycle of R-CHOP and were randomly assigned to five cycles of Glofit-Pola-R-CHP (n = 40) or Glofit-R-CHOP (n = 40), and two cycles of glofitamab consolidation. Enrollment occurred before or after a cycle of R-CHOP. The primary objective was safety and treatment deliverability. Secondary end points included response rates and survival.

RESULTS:

Eighty evaluable patients with a median age of 58 years and total metabolic tumor volume of 842 cm 3 were included and began treatment a median of 14 days from diagnosis. Over 95% of patients completed all therapy and the median relative dose intensity was >94%. Cytokine release syndrome was observed in 21% of patients, all ≤grade 2 and manageable. Overall and complete response rates were 100% and 98%, respectively. At 20.7-month median follow-up, the estimated 2-year progression-free survival and overall survival were 86% and 92%, respectively.

CONCLUSION:

The combination of glofitamab with R-CHOP or Pola-R-CHP is deliverable and results in high rates of durable response in this population of younger patients with high-burden, HR LBCL, supporting its ongoing exploration as a 1L treatment.

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.

210

项与奥德罗奈昔单抗相关的新闻（医药）

2025-09-14

·药明康德

致敬时代丨从“不治之症”，到超90%患者癌细胞减少或几乎“全消失”，数十款新药为这类“血癌”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。今天（9月15日）是世界淋巴瘤宣传日。淋巴瘤是最常见的血液肿瘤。它起源于淋巴系统，主要分为霍奇金淋巴瘤（HL，约占10%）和非霍奇金淋巴瘤（NHL，约占90%）两大类，其中B细胞淋巴瘤又占NHL的85%以上。随着对淋巴瘤病理机制研究和疗法开发的持续推进，尤其是21世纪以来各类创新疗法取得突破，淋巴瘤目前已成为控制率、治愈率最高的恶性肿瘤之一。临床研究数据显示，在多种治疗方案的加持下，当前霍奇金淋巴瘤的治愈率（治愈通常指肿瘤消失且长期不复发）已经能达到75%~80%，早期患者甚至可达90%以上。针对最常见的B细胞淋巴瘤，标准一线治疗方案带来的临床治愈率也可达到70%以上。淋巴瘤的治疗是快速发展的创新技术与药物研发进步的缩影，也是上百年来癌症领域放化疗、靶向治疗、免疫治疗等治疗理念发展的缩影。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，很荣幸见证了包括淋巴瘤在内的各类癌症创新疗法从实验室到临床应用的突破历程，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淋巴瘤创新疗法的研发进程，造福病患。今天这篇文章将再次回望淋巴瘤创新疗法的攻坚历程，向那些以勇气、坚持与热爱迎难而上、为攻克淋巴瘤治疗做出贡献的英雄们致敬。图片来源：123RF 化疗革新时代：癌症治愈曙光乍现提到淋巴瘤，许多人会想到“霍奇金淋巴瘤”。这一名称源于英国病理学家托马斯·霍奇金（Thomas Hodgkin）。1832年，他首次描述了7例以淋巴结和脾脏肿大为特征的病例，并注意到该病可沿淋巴结组有序扩散。此后二十多年，更多学者观察到相似的病例，并确认了托马斯·霍奇金的贡献，以“霍奇金病”命名以示纪念。此后几十年内，学界对霍奇金病的病因进行了大量讨论，多数学者认为它与结核病有关。直到1900年前后，两位医生Carl Sternberg和Dorothy Reed分别详细描述了在显微镜下观察到的霍奇金病患者特有的巨型细胞（即现在所称的Reed-Sternberg细胞），明确将其与结核病区分开来，并确定了诊断霍奇金淋巴瘤的关键依据。相比之下，NHL的发现与分类历程更为复杂。由于其亚型繁多、临床表现复杂，NHL曾长期与白血病混淆不清。直至1956年，学界才基于细胞形态和滤泡结构等特征，建立起现代NHL分类系统。20世纪末期，随着对淋巴细胞生物学认识的深入以及分子病理学的发展，学者们整合形态、免疫表型及遗传学特征，提出了具里程碑意义的REAL分类，进一步推动了淋巴瘤的诊断与分型精准化，后经世界卫生组织（WHO）逐步迭代，形成了现在的淋巴瘤分类和诊断的“世界语言”体系。如今我们知道，大多数非霍奇金淋巴瘤源于B细胞，其余部分来源于T细胞。因为种类繁多，且不同类型的淋巴瘤具有不同的细胞特征、症状和临床进展过程，治疗也相对复杂，需根据不同类型制定不同的治疗方案。几种常见的非霍奇金淋巴瘤亚型，例如弥漫大B细胞淋巴瘤（DLBCL）是最常见类型，侵袭性强，进展快；滤泡性淋巴瘤（FL），是惰性淋巴瘤的代表，生长速度很慢但难以根治；套细胞淋巴瘤（MCL）兼具惰性和侵袭性特征，等等。淋巴瘤的治疗探索也历经百年。1902年，医学界用X射线治疗了第一例霍奇金淋巴瘤，放疗走进淋巴瘤治疗的历史舞台。20世纪40年代，科学家在对一名非霍奇金淋巴瘤患者使用氮芥之后，观察到了明显的肿瘤缩小，成为癌症化疗的开端。1949年，美国FDA批准氮芥气治疗霍奇金淋巴瘤，成为首个获批治疗癌症的化疗药物。此后，更多化疗药物出现，科学家们也基于此开发出多种联合化疗方案。其中尤其值得一提的是发表于1970年前后的MOPP（由4款化疗药组成）等一些联合方案，其使晚期霍奇金淋巴瘤患者的完全缓解率从接近零上升到80%，且约60%达到完全缓解的患者在随访的40年间未复发。这是癌症治疗史上的重要革新，霍奇金淋巴瘤被认为是“第一个通过化疗治愈成人主要器官系统晚期癌症的案例”。期间，研究人员也开发出其他用于治疗DLBCL等非霍奇金淋巴瘤的化疗方案，为控制患者癌症发展发挥了重要作用。世纪之交：抗CD20单抗开启淋巴瘤免疫疗法时代尽管化疗在淋巴瘤治疗中取得了显著成效，但其副作用及复发患者预后不佳等问题，也使临床治疗面临新的挑战。在此背景下，科学家将目光转向人体自身的免疫系统——能否利用免疫系统产生的抗体来对抗癌细胞呢？然而，这一设想的实现需克服多重现实障碍。首先，必须获得足够量的特异性抗体。20世纪70年代，研究人员通过将小鼠淋巴细胞与骨髓瘤细胞融合，成功制备出杂交瘤细胞。该细胞既能在体外无限增殖，又可像B细胞一样大量分泌单克隆抗体。其次，必须找到一种特异性表达于癌细胞表面的抗原。最终，科学家在非霍奇金淋巴瘤B细胞表面发现了CD20抗原。该蛋白仅表达于健康成熟B细胞和癌变B细胞上，这意味着靶向CD20的治疗在清除这两类细胞的同时，人体仍能通过未成熟B细胞再生恢复B细胞功能。CD20因此成为理想的治疗靶点。基于该机制，当时一家名为IEDC的小型医药公司（后与渤健合并）开发出一种对CD20具高亲和力的单克隆抗体——IEDC-C2B8，即后来大名鼎鼎的利妥昔单抗，希望用它来治疗低级别或滤泡性淋巴瘤。1994年，在一次学术会议上，IEDC创始人与基因泰克（2009年被罗氏收购）公司的科学家结识，双方开始合作推进该药物的临床开发和商业化。当时，单克隆抗体在癌症治疗中的潜力尚未得到临床验证，大规模生产此类生物大分子也尚无先例。令人欣喜的是，IEDC-C2B8在临床试验中表现出卓越的疗效：近一半对化疗无应答的NHL患者，经利妥昔单抗治疗后达到完全或部分缓解，单药总缓解率达48%，且不良反应率显著低于传统化疗。1997年，Rituxan（利妥昔单抗，rituximab）获FDA批准上市，用于治疗复发或难治性低级别/滤泡性CD20阳性B细胞NHL，成为历史上首个获批抗癌单克隆抗体，也是NHL的首个靶向疗法。随着研究持续推进，利妥昔单抗与化疗联用也在非霍奇金淋巴瘤中显示出协同增效作用。直到今天，利妥昔单抗仍然具有强大的生命力，利妥昔单抗联合化疗仍然是B细胞淋巴瘤的治疗基础和标准方案，而且不同的用药方案以及新适应症都在持续探索中。利妥昔单抗之后，淋巴瘤治疗领域迎来了单抗药物大爆发。多款CD20单抗如Kesimpta（奥法妥木单抗，ofatumumab）、Gazyva（奥妥珠单抗，obinutuzumab）、安瑞昔（泽贝妥单抗，zuberitamab）、安平希（瑞帕妥单抗，ripertamab）陆续出现，适应症也拓展至弥漫大B细胞淋巴瘤、滤泡性淋巴瘤、套细胞淋巴瘤、慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）等多种B细胞非霍奇金淋巴瘤。它们在减少不良反应的同时，显示出更强的抗肿瘤活性。国际权威期刊《自然》子刊Nature Reviews Drug Discovery于2019年发表的一篇综述指出，在抗CD20靶向疗法作为一线治疗选择的情况下，大多数NHL亚型患者对一线疗法的缓解率在80%以上，三年无进展生存率达到70%左右。除了CD20靶点，一些以B细胞或T细胞表面其它抗原等为靶点的抗体新药在此后数年接连获批上市，治疗不同类型的淋巴瘤。如靶向CD52的Campath（阿仑珠单抗，alemtuzumab）、靶向CCR4的Poteligeo（莫格利珠单抗，mogamulizumab）、靶向CD19的Monjuvi（坦昔妥单抗，tafasitamab）等。同时放射性药物、抗体偶联药物（ADC）也陆续出现，比如靶向CD20的放射性药物Zevalin（替伊莫单抗，ibritumomab tiuxetan）、Bexxar（托西莫单抗，tositumomab）；以及多个靶向不同抗原的ADC，比如靶向CD30的Adcetris（维布妥昔单抗，brentuximab vedotin）、靶向CD79b的Polivy（维泊妥珠单抗，polatuzumab vedotin）、靶向CD19的Zynlonta（替朗妥昔单抗，loncastuximab tesirine）等。随着免疫疗法潜力持续释放，近10年来以抗PD-1抗体、双特异性T细胞衔接器、CAR-T细胞疗法等为代表的新型免疫疗法为淋巴瘤治疗带来新的希望。2016年5月，抗PD-1单抗疗法Opdivo（纳武利尤单抗，nivolumab）获FDA批准首个血液肿瘤领域适应症，用于治疗经典霍奇金淋巴瘤，也由此开启了淋巴瘤领域的免疫检查点抑制剂治疗时代。2017年，FDA批准首款CAR-T细胞疗法Kymriah（tisagenlecleucel），适应症为治疗某些类型的成人大B细胞淋巴瘤。目前，全球范围内已有数款PD-1/PD-L1抑制剂以及近10款CAR-T疗法获批淋巴瘤领域的适应症。 2022年，罗氏开发的“first-in-class”CD20/CD3 T细胞衔接双抗Lunsumio（莫妥珠单抗，mosunetuzumab）在欧盟获得首批，用于治疗复发/难治性滤泡性淋巴瘤成人患者。该产品代表着一种无化疗、现货型（off-the-shelf）的新免疫治疗选择。此后，多款CD20/CD3双抗如Columvi（格菲妥单抗，glofitamab）、Epkinly（艾可瑞妥单抗，epcoritamab）、Ordspono（奥德罗奈昔单抗，odronextamab），相继获监管机构批准上市，为滤泡性淋巴瘤、大B细胞淋巴瘤等B细胞淋巴瘤患者带来新的治疗选择。重磅BTK抑制剂诞生：改写血液肿瘤治疗格局在大分子单抗药物引领淋巴瘤治疗取得突破的同时，小分子靶向抗癌药也逐步兴起。20世纪90年代，研究发现一种名为BTK的酪氨酸激酶在B细胞受体（BCR）信号通路中起关键作用，使其成为B细胞恶性肿瘤领域备受关注的新靶点，一些企业随之布局BTK抑制剂的开发。但由于对共价药物脱靶毒性风险的疑虑，该类研发前景一度不被看好。转机出现在2006年，一家名为Pharmacyclics的公司收购了来自Celera Genomics公司的一个可共价结合BTK的化合物，并敏锐意识到其在B细胞肿瘤治疗中的潜力，开始推进其开发进程。2009年，该小分子化合物启动1期临床试验。2011年，Pharmacyclics报告了其在多种B细胞恶性肿瘤中积极的1b/2期数据。之后不久，强生旗下杨森制药（现强生创新制药）加入合作，共同推进该项目的研发。 2013年11月，该药物以Imbruvica（伊布替尼，ibrutinib）之名获FDA加速批准用于治疗套细胞淋巴瘤（MCL）。如今，伊布替尼已获FDA批准用于十余项适应症，成为多种血液肿瘤的一线标准治疗。因其卓越的临床疗效，伊布替尼一度被誉为“上帝的礼物”。以慢性淋巴细胞白血病/小淋巴细胞淋巴瘤为例，这类非霍奇金淋巴瘤亚型既往依赖化疗，但毒副作用显著。2016年3月，伊布替尼获FDA批准用于一线单药治疗CLL/SLL，成为该领域首个“无化疗”方案。研究显示，伊布替尼可显著延长患者无进展生存期（PFS）和总生存期（OS），5年PFS率达到80.0%。此后，Calquence（阿可替尼，acalabrutinib）、Brukinsa（泽布替尼，zanubrutinib）、Velexbru（tirabrutinib）、宜诺凯（奥布替尼，orelabrutinib）、Jaypirca（匹妥布替尼，pirtobrutinib）等更多BTK抑制剂陆续问世，持续造福套细胞淋巴瘤、CLL/SLL、边缘区淋巴瘤、中枢神经系统淋巴瘤、华氏巨球蛋白血症、滤泡性淋巴瘤等患者。它们在持续提升淋巴瘤治疗效果的同时，也在通过结构优化不断克服现有药物局限性。随着医药科技的不断发展，更多淋巴瘤治疗关键靶点被陆续发现，HDAC抑制剂、PI3K抑制剂、BCL-2抑制剂、JAK1抑制剂、EZH2抑制剂等小分子靶向药物相继涌现，持续推动这一领域治疗格局的革新。目前已获批上市的HDAC抑制剂包括Zolinza（伏林司他，vorinostat）、Beleodaq（贝林司他，belinostat）、爱谱沙（西达本胺，chidamide）等，它们为弥漫性大B细胞淋巴瘤以及多种T细胞淋巴瘤患者提供了新的治疗选择。 PI3K抑制剂也已有多款药物获批上市，包括Zydelig（艾代拉利司，idelalisib）、Copiktra（度恩西布，duvelisib）、Aliqopa（可泮利塞，copanlisib）、因他瑞（林普利塞，linperlisib）等，适应症覆盖了CLL/SLL和滤泡性淋巴瘤。此外，还有一款PI3K/HDAC小分子双靶点抑制剂贝特琳（伊吡诺司他，ifupinostat）已获批治疗弥漫性大B细胞淋巴瘤。在EZH2抑制剂方面，已获批药物包括Ezharmia（valemetostat tosilate）、Tazverik（他泽司他，tazemetostat）、艾瑞璟（泽美妥司他）等，适应症涵盖了滤泡性淋巴瘤、外周T细胞淋巴瘤（PTCL）等。 BCL-2抑制剂中，目前已有Venclexta（维奈克拉，venetoclax）、利生妥（利沙托克拉，lisaftoclax）获批上市，它为CLL/SLL、套细胞淋巴瘤患者带来新治疗选择。 JAK1则是近年来被证实可用于淋巴瘤治疗的全新靶点。JAK1抑制剂高瑞哲（戈利昔替尼，golidocitinib）在中国获批治疗复发或难治的PTCL成人患者。PTCL属于非霍奇金淋巴瘤中生存率最低的类型之一，复发或难治患者的生存预后极差。更多创新疗法涌现，未来可期当前，科学界仍在探索更多的治疗手段，旨在进一步提升患者的生存期和生活质量，向“治愈癌症”的终极目标迈进。数据显示，当下还有数百款在研新药处于临床研究阶段以探索治疗各类淋巴瘤的潜力。它们不仅涵盖CD38、CD22、CD47、ROR1、ITK等新靶点，还涵盖了更丰富的分子类型，如双靶点CAR-T、靶向蛋白降解剂、核酸药物等。与此同时，还有不少研究在探索不同的联合治疗方案，如BCL-2抑制剂+BTK抑制剂等靶向治疗组合、BTK抑制剂联合抗体、BTK抑制剂联合CAR-T，或双特异性抗体联合ADC，等等。正是因为这些丰富的临床治疗选择，目前越来越多的淋巴瘤亚型患者通过现有疗法实现高缓解率和持久疗效。以最常见且具侵袭性的B细胞淋巴瘤——DLBCL为例，近两年多项研究数据显示，BTK抑制剂联合R-CHOP方案（当前的DLBCL基础治疗方案）一线治疗具有良好疗效和安全性，患者客观缓解率（ORR）超过90%，意味着超九成患者肿瘤细胞数明显下降或几乎“全消失”。近期发表的一项针对未经治疗的非生发中心B细胞样型DLBCL的研究还显示，患者完成6周期治疗后的完全缓解率达100%，意味着所有患者的肿瘤细胞“完全消失”。一体化平台赋能淋巴瘤新药开发尽管恶性肿瘤令人望而生畏，但过去几十年，抗肿瘤治疗取得了大量令人振奋的里程碑进展，淋巴瘤治疗领域尤其如此。过去25年间，全球监管机构批准了几十款淋巴瘤创新疗法，其中不少新药还获批多个淋巴瘤适应症。作为创新的赋能者，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。长期以来，药明康德都在支持全球合作伙伴从药物研究发现（R）、开发（D）到商业化生产（M）各个阶段的需求，通过独特的一体化、端到端CRDMO模式，助力突破性疗法加速研发进程、早日惠及患者。在抗击淋巴瘤的漫长征程中，这些振奋人心的成就，既得益于科学家挑战传统的远见与勇气，也离不开转化医学领域中学界与产业界的紧密协作。在此，我们向所有在淋巴瘤治疗道路上孜孜以求、默默奉献的科研与医疗工作者，致以最崇高的敬意。药明康德也将继续与全球合作伙伴携手同行，助力加速创新疗法的开发与落地，为更多患者带来希望与曙光。参考资料： [1] Chaudhari et al. (2019). Non-Hodgkin lymphoma therapy landscape. Nature Reviews Drug Discovery, Retrieved April 16, 2019, from https://www.nature.com/articles/d41573-019-00051-6 [2]Eyre TA et al.(2025)ESMO Guidelines Committee. Lymphomas: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. doi: 10.1016/j.annonc.2025.07.014. [3] DeVita et al.(2008)A history of cancer chemotherapy. Cancer Res. doi: 10.1158/0008-5472.CAN-07-6611. [4] Aisenberg AC.（2000）Historical review of lymphomas. Br J Haematol. doi: 10.1046/j.1365-2141.2000.01988.x. [5]赵曙.（2025） B 细胞淋巴瘤药物治疗进展. 《肿瘤药学》DOI: 10.3969/j. issn. 2095-1264.2025.03.03. 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

免疫疗法

2025-09-05

·FierceBiotech

\'Several concerning observations\': FDA sheds more light on reasons it rejected drugs

The FDA’s correspondence includes the decision not to approve Zealand Pharma’s GLP-2 drug glepaglutide for short bowel syndrome.\n The FDA’s ongoing effort to establish a culture of “radical transparency” saw the agency publish another haul of complete response letters (CRLs) yesterday.The latest batch of 89 rejection letters was uploaded Sept. 4 along with a pledge by the agency to begin publicly releasing this type of communication at the same time the documents are issued to sponsoring companies. As with the initial mailbag of more than 200 CRLs that the FDA made available back in July, a dive into yesterday’s letters sheds further light on the agency\'s often-opaque drug review process.Among the letters are some high-profile decisions for the likes of Ultragenyx’s gene therapy for Sanfilippo syndrome type A, Capricor Therapeutics’ Duchenne muscular dystrophy cell therapy and Replimune’s melanoma drug RP1. The contents of the letters often map onto information already in the public domain, but there are still some fresh insights to be gleaned about the FDA’s decision-making process.‘Numerous unreported adverse events’ The FDA’s correspondence certainly sheds more light on the agency’s decision at the end of last year not to approve Zealand Pharma’s GLP-2 drug glepaglutide in short bowel syndrome. That application—which could have set up glepaglutide as a possible challenger to Takeda’s Gattex—was based on results from a single placebo-controlled phase 3 study dubbed EASE-1.The trial hit its primary endpoint, with twice-weekly doses of glepaglutide reducing weekly parenteral support (PS) volume—a measure of tube feeding—by a statistically significant 5.13 liters at 24 weeks compared to baseline. However, once-weekly doses of glepaglutide failed to yield statistically significant reductions in PS.When Zealand announced that it had received the CRL in December 2024, the company didn’t divulge much detail, only confirming that the agency had “concluded that Zealand Pharma’s application did not meet the full requirements for substantial evidence to establish the efficacy and safety of the to-be-marketed dose of glepaglutide.”The full letter from the FDA, which was uploaded yesterday, gives a more detailed insight into the agency\'s rationale. While acknowledging the twice-weekly dosing endpoint win, the FDA pointed to “numerous uncertainties that limit the interpretability and/or persuasiveness of the results.”These included “observed inconsistencies” in PS as a result of adjustments outside of the trial’s protocol, according to the FDA. The inconsistencies “raise concerns that the observed changes in PS volume may have been impacted by factors other than the drug’s efficacy and may not accurately represent PS volume requirements of the subject,” the FDA said in the letter. The agency also noted that “incomplete or missing documentations of urinary output in the 48 hours prior to study visits” were observed in up to 12% of patients in the EASE-1 trial, as well as in 68% of patients in the follow-on EASE-2 study.Meanwhile, an FDA inspection of one of the study’s clinical investigator sites identified “several concerning observations,” including “numerous unreported adverse events” among six of the nine patients enrolled there. Two of these unreported events were considered “serious” and involved patients being hospitalized due to acute kidney injury or hypomagnesemia, respectively.The FDA’s recommendation was for Zealand to conduct a further trial, and the Danish biotech is on track to kick off that study later this year. In the meantime, the company is awaiting an approval decision for glepaglutide from European regulators.Psychedelic uncertainties When it came to the rejection of Lykos Therapeutics’ application for its MDMA candidate midomafetamine to treat post-traumatic stress disorder, the potential objections had been out in the open for a while. Even before the agency sent the CRL in August 2024, the FDA had voiced concerns in briefing documents about whether a clinical trial for an MDMA treatment could ever be properly blinded, given that the drug “produces profound alterations in mood, sensation, suggestibility and cognition.”The agency’s Psychopharmacologic Drugs Advisory Committee had also been unconvinced of approval, in what was the first instance of an FDA committee reviewing a psychedelic treatment.Summarizing the contents of the CRL at the time, Lykos said the letter had “included concerns that Lykos\' clinical data were insufficient to demonstrate durability along with questions about expectancy bias stemming primarily from participants with prior MDMA use.” Reading the full letter reveals that the FDA also echoed specific prior concerns it had raised about the need to record “positive” effects of the treatment as adverse events for the purposes of the study.“As you were specifically advised, regardless of whether a participant, therapist or physician may find a drug experience to be neutral, positive or favorable, events that are relevant to the abuse potential of a drug or potential for impairment should have been captured and reported,” the FDA wrote in its letter.“Because such events were not captured and reported, the studies failed to adequately characterize the safety of midomafetamine, its acute effects, the duration of impairment, or signals of abuse potential within these studies,” the agency added.The last we heard from Lykos, it hadn’t let this setback get it down. As of January, the biotech had met with the FDA to “chart a path forward for an independent third-party review of prior phase 3 clinical data and an additional phase 3 trial.”A matter of timing Regeneron got off lightly when the FDA rejected its application for the T-cell engager odronextamab to treat patients with follicular lymphoma or diffuse large B-cell lymphoma. Announcing the CRL in March 2024, the pharma was keen to stress that the agency had not identified “any approvability issues.”Regeneron’s original plan had been to enroll patients in various confirmatory phase 3 lymphoma trials that formed part of the wide-ranging Olympia program while it sought accelerated approval. Enrollment in the dose-finding portion of these trials had already begun when the company filed its application, but Regeneron explained at the time of the rejection that the FDA decided “the confirmatory portions of these trials should be underway and that the timelines to completion be agreed prior to resubmission” of the application.A close read of the FDA’s letter suggests the agency was certainly skeptical of Regeneron’s proposed time frames.“The current conduct and projected completion date of any of these Olympia trials in follicular lymphoma do not provide sufficient assurance of timely completion of the trial(s),” the letter reads.When it came to resubmitting the application, the FDA said Regeneron would be wise to “demonstrate sufficient progress in the conduct of the confirmatory portion of the confirmatory trial(s) to provide sufficient assurance of timely completion of the trial(s).\"The pharma returned to the FDA with an updated application in February, but this resulted in another rejection a few weeks ago. This time, Regeneron blamed the decision on problems uncovered during an FDA inspection of an Indiana plant now owned by Regeneron’s manufacturing partner Novo Nordisk.Regeneron can at least take some comfort from the fact that despite these U.S. setbacks, odronextamab secured the green light from European regulators back in August 2024.

$\'Several concerning observations\': FDA sheds more light on reasons it rejected drugs$

临床3期

2025-09-04

·EndPoints

In a first, FDA publishes complete response letters for ongoing drug applications

On Thursday, the FDA finally did what several prior agency commissioners only promised to do: publish redacted complete response letters for drugs that are still under consideration by the agency despite the initial rejection. The 89 letters include some recent high-profile — and sometimes contentious — rejections of drugs from Replimune, Capricor Therapeutics, Stealth BioTherapeutics and many others. And while the letters will add insight into why the FDA turned down the drugs, the action is almost certain to be controversial, or challenged legally, if some companies object to the release of what has long been thought of as proprietary and confidential information. “This definitely seems like a historic first in ensuring transparency,” Reshma Ramachandran, a Yale physician and chair of the Doctors for America FDA Task Force, told Endpoints News . “It’ll be interesting to see if moving forward, FDA will provide actual real-time access to these letters.” The move marks a significant step forward from the agency’s action in July, when it released more than 200 CRLs, but only for products that later won approval . Until now, it’s been up to companies to decide what to share about the CRLs they receive, often raising some doubts about whether they’re being fully transparent with investors and patients. For example, a 2015 study in the BMJ from FDA authors found major discordance between what CRLs said and what companies described in their press releases. Endpoints reviewed many of the CRLs released Thursday and found that they generally aligned with companies’ public disclosures about them. Ramachandran said the release of the CRLs, and talk by the FDA of making more releases, could put pressure on companies to be more transparent and honest in their own communications. Aaron Kesselheim, lawyer and professor at Harvard Medical School, told Endpoints that regulatory science experts have been discussing the possibility of the FDA releasing CRLs for over 15 years. “Why hasn’t the FDA done this before?” Kesselheim asked. “I think it’s a combination of concern about getting sued over inadvertent release of proprietary information and an overly permissive interpretation of trade secrets in which the FDA tends to reflexively agree with manufacturers about certain information being confidential even if it has extremely high public health value and lacks actual commercial value.” Companies that spoke with Endpoints were generally neutral or supportive about the FDA’s action. A Regeneron spokesperson said that the release of its CRL earlier this year for its cancer drug odronextamab doesn’t impact the company’s resubmission “in any way – these disclosures have already been shared in the dedicated and earnings press releases.” Stealth received a CRL in May for its potential treatment for the ultra-rare Barth syndrome, and CEO Reenie McCarthy told Endpoints that the company released the letter in full last month. “We applaud the FDA’s ongoing commitment to transparency and hope this step will facilitate engagement with other rare disease patient groups and expedite needed therapies,” McCarthy said in a statement. Replimune said that the release of its July CRL for its potential advanced melanoma treatment didn’t come as a surprise, with a spokesperson saying the action “is in line with the agency’s commitment.” Analysts at BMO Capital Markets said Thursday that the Replimune CRL was explained well by the company, but further confirmed their concerns regarding a path forward. “While we continue to believe that Replimune likely has an active drug in RP1, the tone of the commentary in the CRL paints a bleak picture for a potential accelerated approval,” an investor note from BMO said. “It is unclear to us what may change the FDA’s opinion in the company’s confirmed type A meeting (given the same leadership remains in place).” Capricor’s potential Duchenne muscular dystrophy drug deramiocel also received a CRL in July , with the agency citing a lack of clinical data showing the effectiveness of the cell therapy. “We were not made aware that the FDA was going to publish the CRL in advance,” Capricor’s CEO Linda Marbán told Endpoints via email. “Based on our internal review and regulatory correspondence, we remain confident in the integrity and completeness of the information we publicly disclosed.” Moving forward, the agency said in a statement that it will “promptly release newly issued CRLs, and when approving applications will release all CRLs associated with that application.” The FDA also said it will publish prior CRLs for withdrawn or abandoned applications, though it will remove confidential commercial information, trade secrets and personal information. Lei Lei Wu and Max Gelman contributed reporting.

加速审批细胞疗法

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外链

KEGG	Wiki	ATC	Drug Bank
D11534	-	-	-

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
复发性弥漫性大B细胞淋巴瘤	欧盟	Regeneron Ireland DAC	2024-08-22
复发性弥漫性大B细胞淋巴瘤	冰岛	Regeneron Ireland DAC	2024-08-22
复发性弥漫性大B细胞淋巴瘤	列支敦士登	Regeneron Ireland DAC	2024-08-22
复发性弥漫性大B细胞淋巴瘤	挪威	Regeneron Ireland DAC	2024-08-22
难治性弥漫性大 B 细胞淋巴瘤	欧盟	Regeneron Ireland DAC	2024-08-22
难治性弥漫性大 B 细胞淋巴瘤	冰岛	Regeneron Ireland DAC	2024-08-22
难治性弥漫性大 B 细胞淋巴瘤	列支敦士登	Regeneron Ireland DAC	2024-08-22
难治性弥漫性大 B 细胞淋巴瘤	挪威	Regeneron Ireland DAC	2024-08-22
复发性滤泡性淋巴瘤	欧盟	Regeneron Ireland DAC	2024-08-22
复发性滤泡性淋巴瘤	冰岛	Regeneron Ireland DAC	2024-08-22
复发性滤泡性淋巴瘤	列支敦士登	Regeneron Ireland DAC	2024-08-22
复发性滤泡性淋巴瘤	挪威	Regeneron Ireland DAC	2024-08-22
难治性滤泡性淋巴瘤	欧盟	Regeneron Ireland DAC	2024-08-22
难治性滤泡性淋巴瘤	冰岛	Regeneron Ireland DAC	2024-08-22
难治性滤泡性淋巴瘤	列支敦士登	Regeneron Ireland DAC	2024-08-22
难治性滤泡性淋巴瘤	挪威	Regeneron Ireland DAC	2024-08-22

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
侵袭性 B 细胞非霍奇金淋巴瘤	临床3期	阿根廷	Regeneron Pharmaceuticals, Inc.	2024-02-15
侵袭性 B 细胞非霍奇金淋巴瘤	临床3期	澳大利亚	Regeneron Pharmaceuticals, Inc.	2024-02-15
侵袭性 B 细胞非霍奇金淋巴瘤	临床3期	巴西	Regeneron Pharmaceuticals, Inc.	2024-02-15
侵袭性 B 细胞非霍奇金淋巴瘤	临床3期	智利	Regeneron Pharmaceuticals, Inc.	2024-02-15
侵袭性 B 细胞非霍奇金淋巴瘤	临床3期	意大利	Regeneron Pharmaceuticals, Inc.	2024-02-15
侵袭性 B 细胞非霍奇金淋巴瘤	临床3期	马来西亚	Regeneron Pharmaceuticals, Inc.	2024-02-15
侵袭性 B 细胞非霍奇金淋巴瘤	临床3期	荷兰	Regeneron Pharmaceuticals, Inc.	2024-02-15
侵袭性 B 细胞非霍奇金淋巴瘤	临床3期	罗马尼亚	Regeneron Pharmaceuticals, Inc.	2024-02-15
侵袭性 B 细胞非霍奇金淋巴瘤	临床3期	新加坡	Regeneron Pharmaceuticals, Inc.	2024-02-15
侵袭性 B 细胞非霍奇金淋巴瘤	临床3期	韩国	Regeneron Pharmaceuticals, Inc.	2024-02-15

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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


ASCO2025	N/A	非霍奇金淋巴瘤 CD20 \| CD3	386	Odronextamab	鹽選廠顧範艱齋衊鬱艱(夢範窪蓋鹽願築鑰膚築) = 41% 憲鏇願鹽築獵糧壓蓋醖 (選積憲網鏇鏇鏇積簾廠 ) 更多	积极	2025-05-30
NCT03888105 (ELM-2, EHA2025)	临床2期	难治性滤泡性淋巴瘤维持 CD20 \| CD3	157	Odronextamab	襯築鏇製艱膚淵憲蓋獵(廠淵蓋鏇遞願淵襯艱淵) = 糧選壓鹽網獵獵窪艱簾膚觸選餘鹹夢遞積網繭 (繭鑰繭鏇糧醖齋淵繭衊 ) 更多	积极	2025-05-22
NCT03888105 (ELM-2, EHA2025)	临床2期	滤泡性淋巴瘤 IFN-γ \| IL-6 \| PD1 ... 更多	-	ODRONEXTAMAB (Marginal Zone Lymphoma (MZL))	製鹽憲鹽鬱顧艱構餘壓(積艱夢簾淵製窪鬱窪鹽) = 淵餘鬱鏇醖鬱獵蓋壓獵鑰築艱鏇遞積憲製繭積 (鏇願簾夢鬱膚壓獵窪糧 ) 更多	-	2025-05-14
NCT03888105 (ELM-2, EHA2025)	临床2期	滤泡性淋巴瘤 IFN-γ \| IL-6 \| PD1 ... 更多	-	ODRONEXTAMAB (Follicular Lymphoma (FL))	製鹽憲鹽鬱顧艱構餘壓(積艱夢簾淵製窪鬱窪鹽) = 醖鹹製鑰選蓋構膚築鑰鑰築艱鏇遞積憲製繭積 (鏇願簾夢鬱膚壓獵窪糧 ) 更多	-	2025-05-14
NCT03888105 (ELM-2, EHA2025)	临床2期	复发性滤泡性淋巴瘤 \| 难治性滤泡性淋巴瘤 CD20 \| BAFF	121	Odronextamab	製衊遞觸鏇膚醖夢顧鏇(廠簾憲築範糧壓艱構鬱) = 68% and 65% 鹽壓鬱艱築糧齋製廠遞 (選繭顧遞餘積選夢夢觸 )	-	2025-05-14
NCT03888105 (ELM-2, Pubmed \| Nat Cancer)	临床2期	弥漫性大B细胞淋巴瘤 CD20 \| CD3	127	Odronextamab	窪餘繭製糧憲齋繭廠襯(鹽願遞鬱築憲築壓餘構) = 獵糧糧鑰夢鬱襯獵願膚鹹糧選製鏇壓夢構構醖 (範獵鏇廠蓋鬱廠製構蓋 ) 更多	积极	2025-03-17
NCT03888105 \| NCT02290951 (ASH2024)	N/A	弥漫性大B细胞淋巴瘤末线 \| 二线 \| 三线	187	奥德罗奈昔单抗	製鑰鏇膚衊膚鏇選蓋遞(衊製蓋構齋醖蓋繭範壓) = 選窪築齋範壓簾壓網蓋製遞膚獵餘餘製鑰廠糧 (簾築窪窪齋簾製獵鹽鏇 ) 更多	积极	2024-12-08
NCT03888105 \| NCT02290951 (ASH2024)	N/A	弥漫性大B细胞淋巴瘤末线 \| 二线 \| 三线	187	奥德罗奈昔单抗 (With the optimized 0.7/4/20 mg step-up regimen)	-	积极	2024-12-08
NCT02290951 (ELM-1, EHA 12024 \| EHA 22024) 人工标引	临床1期	弥漫性大B细胞淋巴瘤	44	Odronextamab	鹹淵蓋夢顧糧選選觸願(衊糧製齋鏇鬱積遞網鏇) = 鹽網窪構淵齋襯製鑰壓網糧襯積繭壓糧鹹齋壓 (製艱鹽獵簾壓廠糧觸願 ) 更多	积极	2024-05-14
NCT03888105 (ELM-2, EHA 12024 \| EHA 22024) 人工标引	临床2期	滤泡性淋巴瘤 CD20 \| CD3	128	Odronextamab	鹽願餘鑰顧鬱繭餘繭選(艱憲鹹夢蓋範簾廠顧衊) = 顧願蓋窪鹹壓窪憲範淵繭夢憲願築築鏇遞膚選 (淵簾繭製網餘顧願簾壓 ) 更多	积极	2024-05-14
NCT03888105 \| NCT02290951 (ELM-2, EHA2024) 人工标引	临床1/2期	滤泡性淋巴瘤 \| 弥漫性大B细胞淋巴瘤 CD20 \| CD3 \| cytokines	507	Odronextamab 80 mg QW	積獵網憲構廠積構糧蓋(餘糧選餘憲廠壓壓網積) = 艱簾膚鬱鬱觸簾築艱鏇膚膚簾襯窪壓襯壓壓壓 (願鹽構簾鏇範獵願簾糧 )	积极	2024-05-14
NCT03888105 \| NCT02290951 (ELM-2, EHA2024) 人工标引	临床1/2期	滤泡性淋巴瘤 \| 弥漫性大B细胞淋巴瘤 CD20 \| CD3 \| cytokines	507	Odronextamab 160 mg QW	積獵網憲構廠積構糧蓋(餘糧選餘憲廠壓壓網積) = 壓衊範積鏇顧廠網製遞膚膚簾襯窪壓襯壓壓壓 (願鹽構簾鏇範獵願簾糧 )	积极	2024-05-14
NCT03888105 (ELM-2, EHA2024)	临床2期	滤泡性淋巴瘤 \| 难治性滤泡性淋巴瘤 \| 弥漫性大B细胞淋巴瘤 ... ctDNA \| MRD \| MYC/BCL2/BCL6 rearrangement ... 更多	-	Odronextamab 80 mg (FL)/160 mg (DLBCL) weekly in C2-4, then 160 mg (FL)/320 mg (DLBCL) every 2 weeks	蓋窪構鬱淵網窪範網醖(鑰襯襯壓齋願淵積選膚) = 顧網鹽選製廠襯憲鑰願網積遞淵壓廠鏇廠艱醖 (衊衊鑰醖蓋餘選糧選網 )	积极	2024-05-14
NCT03888105 (ELM-2, EHA2024)	临床2期		-	Placebo	蓋窪構鬱淵網窪範網醖(鑰襯襯壓齋願淵積選膚) = 齋築鏇簾鹽範夢淵遞壓網積遞淵壓廠鏇廠艱醖 (衊衊鑰醖蓋餘選糧選網 )	积极	2024-05-14