A Randomized International Phase 3 Trial of Imatinib and Chemotherapy With or Without Blinatumomab in Patients With Newly-Diagnosed Philadelphia Chromosome-Positive or Philadelphia Chromosome-Like ABL-Class B-Cell Acute Lymphoblastic Leukemia

This phase III trial compares the effect of the combination of blinatumomab with dasatinib and standard chemotherapy versus dasatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (PH+) or Philadelphia chromosome-like (Ph-Like) ABL-class B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib in combination with standard chemotherapy may work better in treating patients with PH+ or Ph-Like ABL-class B-ALL compared to dasatinib and chemotherapy alone.

开始日期2025-05-29

申办/合作机构

National Cancer Institute

NCT06317662

/ Not yet recruiting临床2期IIT

A Phase 2 Study of Blinatumomab in Combination With Chemotherapy for Infants With Newly Diagnosed Acute Lymphoblastic Leukemia With Randomization of KMT2A-Rearranged Patients to Addition of Venetoclax

This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged [R]) or without a KMT2A gene rearrangement (KMT2A-germline [G]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.

开始日期2025-04-26

申办/合作机构

National Cancer Institute

NCT06836973

/ Not yet recruiting临床2/3期IIT

Efficacy and Safety of Blinatumomab for Treatment of Refractory Generalized Myasthenia Gravis.

The goal of this clinical trial is to evaluate the efficacy and safety of Blinatumomab in the treatment of refractory generalized myasthenia gravis, with the expectation of offering a new therapeutic option for refractory patients. The main questions it aims to answer are:
* Does Blinatumomab improve patients' clinical symptoms?
* Is Blinatumomab safe for the treatment of myasthenia gravis?
Participants will:
* Receive two cycles of intravenous Blinatumomab infusion, each lasting 5 days, with a 1-week interval between cycles.
* Visit the clinic once every 4 weeks for checkups and tests.
* Keep a diary of their symptoms and the types and dosages of medications.

开始日期2025-03-01

申办/合作机构-

100 项与贝林妥欧单抗相关的临床结果

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100 项与贝林妥欧单抗相关的转化医学

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100 项与贝林妥欧单抗相关的专利（医药）

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977

项与贝林妥欧单抗相关的文献（医药）

2025-12-31·Hematology

Blinatumomab added to conditioning regimen of allogeneic hematopoietic stem cell transplantation for adult MRD - positive acute lymphoblastic leukemia: a single-center case series

Article

作者: Zhang, Congxiao ; Zhao, Yanmin ; Shi, Jimin ; Liu, Meng ; Huang, He ; Yu, Jian ; Fu, Huarui ; Yang, Li ; Fu, Hui

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) remains the mainstay of treatment for adults with high-risk acute lymphoblastic leukemia (ALL). Due to the crucial role of measurable residual disease (MRD) before Allo-HSCT in predicting relapse and the promising anti-leukemia effect of blinatumomab, we documented a short-course, low-dose conditioning regimen incorporating blinatumomab for Allo-HSCT in three ALL patients with positive MRD. Following the administration of the blinatumomab-containing conditioning regimen, all patients attained complete remission (CR) with negative MRD status, and no severe adverse events were observed. After a 2-year follow-up, 2/3 of patients remained disease-free and attained long-term survival following transplantation. These cases indicated a short-term blinatumomab conditioning regimen may effectively prolong patient survival, improve prognosis, and offer a safe and cost-effective treatment for high-risk ALL patients with positive MRD. The addition of blinatumomab to the conditioning regimen of Allo-HSCT is feasible for high-risk ALL patients with positive MRD.

2025-03-01·JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY

Contributions of Pediatric Hematology/Oncology to the Diagnosis, Treatment, and Cure of Acute Lymphoblastic Leukemia—Part 2b (Numbers 16 to 20)

Article

作者: Miller, Denis R

This offering represents part 2b of a second set of 5 additional contributions of pediatric hematology/oncology to the diagnosis, treatment, and potential cure of precursor B-cell acute lymphoblastic leukemia. It contains numbers 16 to 20 and includes (16) allogeneic hematopoietic stem cell transplantation, newer immunotherapies including (17) blinatumomab, and (18) inotuzumab ozogamicin, (19) ploidy, and (20) creation of the “day hospital” to administer outpatient care to children with acute lymphoblastic leukemia and other cancers. These and the other reviewed contributions have had a significant role in improving the quality and duration of the lives of children, most of whom faced tragic and painful death back in the 1950s and 1960s. Most of our early optimistic goals were achieved and have benefitted substantially our patients, providing those of us who participated in many of these key clinical trials, a profound sense of accomplishment.

2025-03-01·AMERICAN JOURNAL OF HEMATOLOGY

Hyper‐CVAD and Sequential Blinatumomab Without and With Inotuzumab in Young Adults With Newly Diagnosed Philadelphia Chromosome‐Negative B‐Cell Acute Lymphoblastic Leukemia

Article

作者: Alvarado, Yesid ; Kantarjian, Hagop ; Haddad, Fadi G. ; Ravandi, Farhad ; Yilmaz, Musa ; Kadia, Tapan ; Ferrajoli, Alessandra ; Sasaki, Koji ; Short, Nicholas J. ; Garris, Rebecca ; Pemmaraju, Naveen ; Senapati, Jayastu ; Jabbour, Elias ; Jain, Nitin

ABSTRACT:

Adding inotuzumab ozogamicin (InO) to hyper‐CVAD and blinatumomab may improve outcomes in newly diagnosed Philadelphia chromosome (Ph)‐negative B‐cell acute lymphoblastic leukemia (B‐ALL). Patients with newly diagnosed B‐ALL received up to four cycles of hyper‐CVAD followed by four cycles of blinatumomab. Beginning with patient #39, InO 0.3 mg/m2 was added on Days 1 and 8 to two cycles of high‐dose methotrexate and cytarabine, and two cycles of blinatumomab. The primary endpoint was the relapse‐free survival (RFS) rate. Seventy‐five patients were treated (median age of 33 years; range, 18–59), of whom 37 (49%) received hyper‐CVAD with blinatumomab and InO (cohort 2). Measurable residual disease (MRD) negativity by next‐generation sequencing (sensitivity: 1 × 10−6) was achieved in 79% of patients in cohort 2. The median follow‐up was 44 months (range, 13–90) overall, and 26 months (range, 8–39) in cohort 2. For the entire cohort, the estimated 3‐year RFS rate was 82% and the 3‐year overall survival rate was 90%. These rates were 90% versus 74% (p = 0.06) and 100% versus 82% (p = 0.01) in patients who did or did not receive InO, respectively. No sinusoidal obstruction syndrome was observed. In summary, hyper‐CVAD with blinatumomab and InO improved the outcomes of patients with newly diagnosed B‐ALL.

421

项与贝林妥欧单抗相关的新闻（医药）

2025-02-26

·BiG生物创新社

方兴未艾的双抗市场：国产20亿人民币，全球130亿美元

作者｜小麦近些年来，随着技术的进步，双抗药物得到快速发展。2024年，全球双抗药物市场规模达到约130亿美元。其中罗氏的用于治疗血友病的Hemlibra全球销量最高，2024年销售额达到45.03亿瑞士法郎（约53.61亿美元）。其次是罗氏的眼科药物Vabysmo增长迅速，2024年销售额为38.64亿瑞士法郎（约46.0亿美元），加上Columvi和Lunsumio，罗氏双抗规模已超百亿美元，占有绝对领先地位（图1）。在我国，康方生物的两款双抗药物（开坦尼和依达方）表现突出，2024年合计销售额预计超过3亿美元。这表明中国药企在全球双抗市场中已占据重要地位。图1. 获批上市的双抗药物信息 01 新颖双抗结构和技术早在1960年，纽约罗斯威尔公园纪念研究所的Nisonoff及其合作者在Science发表的论文中首次提出了双特异性抗体的概念。但是直到 2009年4月，首个双抗Catumaxomab卡妥索单抗被欧洲药品管理局（EMA）批准上市。截止目前，全球已获批17款双抗药物（图1）。从获批的双抗药物结构中，我们可以看到双抗技术得到了快速发展，双抗的设计和生产逐渐迎来了革新。早期的双特异性抗体主要通过化学偶联或杂交杂交瘤技术制备，但存在制备复杂、稳定性差等问题。后来随着基因工程、杂交瘤技术、生物大分子重组等技术的飞速发展，双抗的技术和类型都得到很大的改善，新的双抗技术脱颖而出，包括BiTEs、DART和TandAb等。 BiTE免疫疗法（Bispecific T-cell Engager，双特异性T细胞衔接器）是一种创新的免疫治疗技术，即以T细胞作为效应细胞的双特异性单链抗体，它是采用单链抗体技术，将两个不同抗体的重链及轻链可变区连接在一条多肽链上。 BiTEs具有两个抗原结合部位，可以同时和T细胞及癌细胞表面的抗原分子结合，从而有效地激活效应T细胞来达到杀伤病变细胞的目的（图2）[1]。图2. BiTE和DART示意图 BiTEs具有以下优点： 1.高效性，能够显著增强T细胞对肿瘤细胞的杀伤作用，即使是在T细胞数量较少的情况下。 2.特异性，通过靶向肿瘤特异性抗原，BiTE疗法能够精准地攻击肿瘤细胞，减少对正常细胞的损伤。 3.广泛适用性，BiTE疗法可以针对多种肿瘤特异性抗原进行设计，具有广泛的应用潜力。 DART技术（Dual-Affinity Re-Targeting）是由MacroGenics公司和Servier公司联合开发的一种双特异性抗体构建技术。与BiTEs相比，DART具有更有利的结构和生物学特性，包括更大的稳定性和将T细胞毒性靶向恶性细胞的最佳重定向。基于DART技术开发的双抗分子是由两条多肽链结合形成的异源二聚体抗体。其构建原理是将一个抗体可变区的VH和VL序列分别与另一个抗体可变区的VL和VH序列连接，并在两条多肽链的C末端引入半胱氨酸，通过半胱氨酸形成链间二硫键，增强了抗体的稳定性和抗原结合能力（图3）[2]。图3. BiTEs、DART和TandAb结构图 TandAb是一种四价双特异性抗体，由两条多肽链反向配对形成同源二聚体分子，其结构为Fv1-Fv2-Fv2-Fv1，包含4个单链可变片段（scFv），能够同时结合两种抗原，且每种抗原有两个结合位点，这种结构显著增强了抗体的结合能力和效力（图3）。 TandAb可以通过多种方法生成，包括重组DNA技术、化学交联和融合蛋白方法。其中，重组DNA技术是主要的生成方式，通过将两个不同的Fv片段串联，形成四价双特异性分子。 TandAb技术凭借其独特的结构设计和高效的功能，在双特异性抗体领域展现出强大的应用前景，为癌症治疗提供了新的策略。 02 代表性双抗药物 2.1 Hemlibra（艾美赛珠单抗） Hemlibra是日本中外制药株式会社（Chugai Pharmaceutical）发现，并由中外制药和罗氏共同开发由罗氏研发的一种双特异性因子IXa和因子X定向抗体，可桥接活化的 IX 因子和 X 因子以替换缺失的活化因子 VIII 的功能，恢复A型血友病患者的凝血过程（图4）[3]。图4. Hemlibra作用机制 Hemlibra于2017年11月首次被FDA批准上市并于2018年被FDA扩增新适应症，适用于成人和儿童血友病A患者，无论是否伴有因子VIII抑制剂，用于预防或减少出血事件的发生。 Hemlibra是近20年来FDA批准的首个用于治疗A型血友病的创新药物，凭借其便捷的给药方式和良好的疗效，在血友病A治疗领域占据重要地位。 2018年11月，Hemlibra在中国获批，成为国内首款上市的双特异性抗体药物。截至2024年，Hemlibra已在全球100多个国家获批用于治疗体内存在凝血因子VIII抑制物的A型血友病患者，并在80多个国家获批用于体内不存在凝血因子VIII抑制物的患者。 Hemlibra的研发是迄今为止最大的A型血友病临床研究项目之一，包括多个关键性III期HAVEN研究（HAVEN-1、HAVEN-2、HAVEN-3、HAVEN-4）。这些研究验证了Hemlibra在不同患者群体中的安全性和有效性，包括存在或不存在凝血因子VIII抑制物的患者。 Hemlibra自2017年上市后销售额逐年上升，并于2020年成功突破20亿美元销售额大关，成为重磅品种。2021年，Hemlibra全球销售额为30.88亿瑞士法郎（约34.34亿美元，按当下1瑞士法郎约等于1.112美元，下同），同比增长41%；2022年Hemlibra销售额为38.23亿瑞士法郎（约42.51亿美元），同比增加27%，2023年销售额达到41.47亿瑞士法郎（约49.3亿美元），2024年Hemlibra销售额达到45.03亿瑞士法郎，同比增长12%（图5）[4]。图5. Hemlibra的销售额 2.2 Vabysmo（Faricimab） Vabysmo （Faricimab）是由罗氏开发的第一个获批用于眼部疾病的双特异性抗体，作用于血管生成素-2（Ang-2）和血管内皮生长因子-A（VEGF-A），Ang-2和VEGF-A通过破坏血管稳定、导致新的渗漏血管形成和增加炎症，从而导致视力丧失。通过阻断涉及 Ang-2 和 VEGF-A 的通路，Vabysmo 可以抑制许多威胁视力的视网膜疾病相关的两条信号通路（图6）。图6. Vabysmo结构与作用机制 Vabysmo 在全球100多个国家获得批准，包括美国、日本、英国和欧盟等，用于治疗新生血管性或“湿性”年龄相关性黄斑变性和糖尿病性黄斑水肿患者等。 2022年1月，Vabysmo首次获 FDA 批准上市，获批适应症有湿性年龄相关性黄斑变性（wAMD）和糖尿病黄斑水肿（DME）。 2023年10月27日，FDA批准Vabysmo用于治疗视网膜静脉阻塞（RVO）患者，成为继wAMD和DME之后第三项获批适应症。 2024年7月，罗氏公布了Vabysmo治疗DME的RHONE-X四年临床试验数据。结果显示，Vabysmo在接受长达四年治疗的DME患者中耐受性良好，超过90%的患者达到DME症状消失的标准。在该研究中，近80%的患者将治疗间隔延长至每三个月或四个月一次，同时保持了视力改善。 2024年ARVO会议上，在对关键性TENAYA（NCT03823287）和 LUCERNE （NCT03823300）试验的事后分析中，Philip P Storey 医学博士提供的结果证明了Vabysmo延长的治疗结果，以及其将剂量减少到每20周一次的潜力。这项为期两年的研究在 wAMD 患者中比较了Vabysmo与Eylea（阿柏西普）（每 8 周给药一次），结果显示近80%的Vabysmo患者实现了12周或16周的给药间隔。此外，该研究确定，56%每16周给药一次的患者可以使用相同的标准延长至每20周给药一次，而44%的患者由于解剖变化（例如中央子视野厚度增加）不符合这种延长的条件[5]。 Elevatum（NCT05224102）是一项为期 1 年的4 期、多中心、开放标签、单臂、1 年试验，包括黑人或非裔美国人的患者（占总入组人数的 ~45%）；西班牙裔或拉丁美洲人（占总入学人数的 ~45%）；或美洲原住民、阿拉斯加原住民、夏威夷原住民或太平洋岛民（占总入学人数的 ~10%）。将从 47 个地点招募美国和肯尼亚的大约 120 名未接受过治疗的 DME 患者（年龄≥ 18 岁）。在ELEVATUM 4期研究中，Vabysmo在种族和民族代表性不足的DME患者群体中显示出显著的视力改善，平均视力表改善12.3个字母（约2.5行），这一效果在不同种族和民族群体中保持一致[6]。 2024年12月13日，罗氏宣布欧洲药品管理局已批准 Vabysmo（faricimab） 6.0 mg 单剂量预充针（PFS）用于治疗nAMD、DME和RVO后黄斑水肿。这三种疾病共同影响了欧盟（EU）的900多万人。 Vabysmo PFS 是第一个也是唯一一个含有双特异性抗体的预充针，为目前可用的 Vabysmo 西林瓶提供了一种方便的替代品[7]。 Vabysmo自上市以来，销售额一直表现不错，2022年它的全球销售额达到5.91亿瑞士法郎（6.6亿美元），2023年全球销售额达到23.6亿瑞士法郎（26.34亿美元），2024年全球销售额高达38.64亿瑞士法郎（约46.0亿美元）（图7）[4]。图7. Vabysmo近两年各个季度销售额 2.3 Blincyto（博纳吐单抗） Blincyto是由安进研发的全球首个CD19-CD3双特异性T细胞接合器（BiTE）药物，由两个主要片段抗CD3 scFv（VL-VH）和抗CD19 scFv（VL-VH）组成，于2014年12月3日获FDA批准上市，用于治疗复发的费城染色体阴性的B细胞急性淋巴性白血病（B-ALL）。 2022年12月，Mark等人在ASH会议上报道了Blincyto的ECOG-ACRIN E1910 3期试验结果：中位随访时间为43个月时，Blincyto组和化疗组中位总生存期（OS）分别为未达到和71.4个月（HR=0.42，95％CI：0.24 -0.75）（图8）[8]。图8. ECOG-ACRIN E1910 3期试验结果 2024年6月14日，安进宣布FDA已批准Blincyto 用于治疗巩固期 CD19 阳性费城染色体阴性 B 细胞前体急性淋巴细胞白血病 (B-ALL) 的成人和儿童一个月或一个月以上的患者，无论可测量的残留疾病 (MRD) 状态如何。此次批准是 Blincyto的第三个适应症，主要基于 ECOG-ACRIN 癌症研究组领导的 3 期 E1910 临床试验，该试验研究了接受诱导后巩固治疗的新诊断的费城染色体阴性 B 细胞淋巴细胞淋巴瘤患者，旨在深化缓解以获得持久反应。研究结果表明，与单纯化疗相比，Blincyto加入多期巩固化疗显示出更好的OS。Blincyto联合化疗组 (n=112) 的3年OS为84.8%，化疗组 (n=112) 的 3 年OS为69%，OS风险比为0.42。中位随访期为4.5年，Blincyto联合化疗组的5年OS为82.4%，化疗组为62.5%。 2025年1月29日，欧盟委员会基于ECOG-ACRIN癌症研究组主导的3期E1910临床试验结果批准Blincyto用于新诊断的CD19阳性、费城染色体阴性B细胞前体急性淋巴细胞白血病（B-ALL）成年患者的巩固治疗。 Blincyto自上市后销售额稳步增长，2021年达到4.72亿美元，然后可能由于Blincyto半衰期仅 2 小时，患者需要频繁给药，以及其它药物的竞争导致销售额在2022年下滑至3.36亿美元，不过由于BB-ALL患者的广泛处方销售额得到剧增，2023年Blincyto销售额达到8.61亿美元，2024年第四季度销售额为3.81亿美元，全年销售额达到15.9亿美元（图9）。图9. Blincyto销售额 2.4 卡妥索单抗（Catumaxomab）卡妥索单抗是首个获批的靶向CD3和EpCAM的双特异性抗体，是一种三单抗（Triomab）形式，它具有两个特异性抗原结合位点和一个功能性Fc结构域，能够同时靶向肿瘤细胞上的上皮细胞黏附分子（EpCAM）和T细胞上的CD3分子（图10）。图10. 卡妥索单抗结构与作用模式卡妥索单抗于2009年获得欧盟（EMA）批准上市，用于治疗恶性腹水。但是卡妥索单抗上市后市场表现不佳。从2009年至2013年，卡妥索单抗的全球销售额持续低迷，分别为166万、332万、443万、454万和270万美元。这种持续的市场表现不佳最终在2017年6月正式退市。尽管如此，卡妥索单抗在临床试验中展现出的疗效并不差，尤其是在治疗因胃癌导致的恶性腹水方面表现出色。基于此，凌腾医药重启了卡妥索单抗在国内的开发。2020年7月，卡妥索单抗开展了伴腹膜转移胃癌的国际多中心三期临床试验。2021年4月，卡妥索双抗获得国家药品监督管理局批准的一项用于治疗非肌层浸润性膀胱癌（NMIBC）的1/2期（ NCT04799847）的临床试验许可。 2022年11月，凌腾医药欧洲合作伙伴Lindis Biotech 在14届欧洲泌尿系统癌症多学科大会（EMUC）上公布了卡妥索单抗CATUNIBLA I期临床试验最新结果：卡妥索单抗在NMIBC中显示良好的安全性和初步疗效。 2025年2月14日，Lindis Biotech递交的卡妥索单抗上市许可申请（MAA）已获得欧洲委员会（EC）批准，用于腹腔内治疗EpCAM阳性且不适合进一步全身抗肿瘤治疗的成人患者的恶性腹水。这标志着卡妥索单抗在全球范围内重新获得认可，并为恶性腹水患者带来了新的治疗希望。 2.5 开坦尼和依达方中国双抗市场竞争激烈，康方生物凭借开坦尼（卡度尼利单抗）和依方达（依沃西单抗）等产品在肿瘤免疫双抗领域占据重要地位。开坦尼是由康方生物研发的靶向PD-1和CTLA-4 的一种对称的四价双特异性抗体，具有可结晶片段（Fc），于2022年6 月 29 日首次在国内获批上市，用于既往接受过含铂化疗治疗失败的复发或转移性宫颈癌患者（图11）。图11. 开坦尼的结构开坦尼是中国自主研发的首款双特异性抗体药物，也是全球首个获批的PD-1/CTLA-4 免疫双抗，具有里程碑式的意义。 2024年9月，开坦尼联合含铂化疗方案获批用于局部晚期不可切除或转移性胃或胃食管结合部腺癌患者的一线治疗。 2024年9月，开坦尼联合方案一线治疗晚期胃癌全人群适应症已获国家药品监督管理局（NMPA）批准上市。该适应症的获批是基于Ⅲ期COMPASSION-15（AK104-302）研究的优异阳性结果：无论PD-L1表达水平如何，开坦尼联合方案相较于化疗能显著延长患者的总生存期并降低死亡风险，对于肿瘤治疗的客观缓解和远期生存获益尤为显著[9]。开坦尼已被纳入多个临床治疗指南，包括《CSCO免疫检查点抑制剂临床应用指南（2024版）》、《基于PD-L1蛋白表达水平的胃癌免疫治疗专家共识（2023年版）》等，2024年11月，开坦尼被纳入《CACA胃癌整合诊治指南2024版》，成为唯一不限PD-L1表达的优先推荐肿瘤免疫治疗药物。依达方是由康方生物自主研发的全球首创PD-1/VEGF双特异性肿瘤免疫治疗药物。这是一种四价双特异性抗体，融合了抗PD-1单抗的单链可变片段（scFv）和抗VEGF单抗的完整结构。依达方于2024年5月获得NMPA批准上市，用于治疗EGFR-TKI治疗失败后的局部晚期或转移性非鳞状非小细胞肺癌（nsq-NSCLC）。依达方是全球第一个获批上市的“肿瘤免疫+抗血管生成”机制的双特异性抗体新药，也是中国第二个获批上市独立自主的双特异性抗体新药[10]。依达方获批是基于一项在中国开展的随机、双盲、多中心III期临床研究（AK112-301/HARMONi-A）结果。研究结果显示：依达方联合化疗组的中位PFS为7.1个月，显著优于对照组的4.8个月（HR=0.46，P<0.001），降低了54%的疾病进展或死亡风险；数据成熟度达到52%时，依沃西单抗联合化疗组的中位OS为17.1个月，对照组为14.5个月，降低了20%的死亡风险[11]。目前，依达方还在进行多项全球多中心临床研究，包括一线治疗鳞状非小细胞肺癌（sqNSCLC）的3期研究以及与化疗联合治疗EGFR突变非鳞状NSCLC的全球多中心3期研究等。令人欣喜的是依达方已获得海外授权。康方生物与Summit Therapeutics达成合作，授予其在美国、加拿大、欧洲、日本等地区的开发和商业化权利。Summit也找到辉瑞，与后者的ADC药物开展联合用药研究，不断放大这款双抗药物的潜力。此外，国产双抗出海交易在2024年呈现大爆发态势，如同润生物与默沙东达成的CD3/CD19双抗交易，金额高达13亿美元。小结双抗技术得到快速发展，从早期的主要通过化学偶联或杂交杂交瘤技术制备到现在发展了很多新的技术，如BiTEs、DART和TandAb等，双抗药物的稳定性和活性也得到了大幅度提升。双抗药物的市场规模也在快速发展，根据市场分析，预计从2024年到2033年，全球双抗药物市场将以37.5%的复合年增长率增长，到2033年市场规模将达到约1926亿美元。主要参考文献 1.Maria-Elisabeth Goebeler et.al, T cell-engaging therapies — BiTEs and beyond, Nat Rev Clin Oncol. 2020 Jul;17(7):418-434. 2.Sumit Goswami et.al, Developments and Challenges for mAb-Based Therapeutics, Antibodies 2013, 2, 452-500 3. Takehisa Kitazawa et.al, A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model, Nat Med. 2012 Oct;18(10):1570-4.4. Roche Full Year Results 2024 5. ARVO conference unveils positive Vabysmo data 6. Elevatum study design and rationale: a phase 4 trial of faricimab (VABYSMO) in underrepresented patients with DME 7. Roche’s Vabysmo prefilled syringe (PFS) approved in the EU for three retinal conditions that can cause blindness 8. Consolidation Therapy with Blinatumomab Improves Overall Survival in Newly Diagnosed Adult Patients with B-Lineage Acute Lymphoblastic Leukemia in Measurable Residual Disease Negative Remission: Results from the ECOG-ACRIN E1910 Randomized Phase III National Cooperative Clinical Trials Network Trial 9. 唯一不限PD-L1表达优先推荐的免疫药物，开坦尼®被纳入《CACA胃癌整合诊治指南2024版》 10. 康方生物PD-1/VEGF双抗新药依达方®获批上市 11. Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous non-small cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor treatment (HARMONi-A): A randomized, double-blind, multi-center, phase 3 trial. 活动预告 2月27日，苏州播禾破局JPM2025：AI药物研发如何大有可为？｜BT/IT 07期 ▼ 共建Biomedical创新生态圈！如何加入BiG会员？

免疫疗法

2025-02-26

·PMLiVE

Amgen’s Blincyto recommended by NICE for new adult leukaemia indication

Amgen’s Blincyto (blinatumomab) has been recommended by the National Institute for Health and Care Excellence (NICE) to treat certain cases of acute lymphoblastic leukaemia (ALL). The health technology assessment agency has recommended in final draft guidance that the immunotherapy be used on the NHS in combination with chemotherapy to treat adults with Philadelphia chromosome-negative CD19-positive B-cell precursor ALL in the consolidation phase, a phase of frontline treatment for ALL which is aimed at killing any remaining leukaemia cells. Eligible patients must also be minimal residual disease-negative, meaning they have responded well to initial therapy and have no detectable cancer cells. NICE’s decision comes two months after the Medicines and Healthcare products Regulatory Agency (MHRA) approved the drug for the same indication. This was supported by positive results from the late-stage E1910 trial led by the ECOG-ACRIN Cancer Research Group. The study showed that Blincyto added to multiphase consolidation chemotherapy was associated with superior overall survival (OS) and relapse-free survival (RFS) compared to chemotherapy alone. With a median follow-up of 4.5 years, the five-year OS was 82.4% in the Blincyto plus chemotherapy cohort versus 62.5% in the chemotherapy group, while the five-year RFS was 77% in the Blincyto/chemotherapy arm versus 60.5% for chemotherapy alone. Approximately 300 adults are diagnosed with ALL, a type of blood cancer that develops in the bone marrow, in the UK every year, with B-cell ALL accounting for the majority of cases. Although up to 90% of adult patients will achieve an initial haematologic complete remission after front-line treatment, as many as 50% will experience relapse and need a second line of therapy. Administered as an intravenous infusion and already approved in the UK to treat certain cases of B-ALL, Blincyto is a bispecific T-cell engager molecule designed to target CD19 surface antigens on B cells. This helps the body’s immune system recognise and destroy cancer cells that might be left behind after initial treatment. Around 80 adults per year could benefit from the Blincyto combination treatment, which will be available to eligible patients immediately through the NHS. Helen Knight, director of medicines evaluation at NICE, said: “This treatment could give patients precious extra months and potentially years with their loved ones. The evidence showing how well it works is really compelling.”

临床结果免疫疗法上市批准

2025-02-22

·SYNAPSE

The Dual Boom of Bispecific Antibodies: Market and Drug Discovery Pipeline

Bispecific antibodies (BsAbs) are recombinant molecules that contain two different antigens or epitopes identifying binding domains. They have gained broad potential in preclinical and clinical investigations in a variety of tumor types following regulatory approval of newly developed technologies involving bispecific and multispecific antibodies. CD3+ bispecific T-cell engaging antibodies exert function in Hematological Malignancies and recruit immune cells into the solid tumor microenvironment for cancer immunotherapy.Booming marketIn fact, over 85% of bispecific antibodies in clinical trials are being designed as cancer treatments. In Synapse database, as of 2022, six bispecific antibodies have been approved by the FDA and/or EMA for cancer immunotherapy. The first approval, Catumaxomab, was later withdrawn from the EU market in 2017. Three other bispecific antibodies gained approval in 2022. Additionally, marketing applications for five bispecific antibodies in late-stage trials may be submitted by the end of 2023. 15 clinical studies recorded by SynapseCurrently over 600 bispecific antibodies are under investigation, as the sector is projected to grow to more than $30 billion over the next five years. Major pharmaceutical companies are increasingly interested in exploring and investing in this promising immunotherapy approach. Diverse architectures & actionsSeveral architectures have been developed for BsAbs, each with different structures and mechanisms of action. IgG-like BsAbs are the most common and featured with an IgG-like structure with two different antigen-binding domains. Asymmetric IgG-like BsAbs possess one heavy chain and one light chain from each antigen-binding domain, while symmetric IgG-like BsAbs have two heavy chains and two light chains from each antigen-binding domain. Some examples of IgG-like BsAbs include blinatumomab and catumaxomab. Diabodies, on the other hand, are small BsAbs that lack the Fc region and have two antigen-binding domains connected by a short linker. Their small size allows them to penetrate solid tumors more effectively than larger antibodies. Notable members from the diabodies family includes MT110 and RG7386. A third type of BsAbs, known as dual-affinity retargeting (DART) molecules, are bispecific single-chain antibodies that have two different antigen-binding domains connected by a flexible linker. Due to their smaller size, similar to diabodies, as well as the high stability, they could be produced in large quantities and have a long shelf life. Molecules such as CD3xCD19 DART and CD3xCD123 DART fall into this category. Bispecific antibodies exert anti-tumor effects in the immunosuppressive tumor microenvironment.And there’s the BiTEs, which are bispecific T-cell engagers with one binding domain for a tumor antigen and another for the T-cell receptor. Their signature action is bringing T cells into close proximity with tumor cells, leading to T-cell activation and tumor cell killing. BiTEs have shown promising results in hematological malignancies and are being investigated in solid tumors. The two binding domains offer BsAbs unique advantages otherwise impossible. A particular kind of BsAbs, checkpoint inhibitors, are raising high hopes among scientists, who believe that they have the potential to revolutionize anticancer treatment. The checkpoint inhibitor works by a smart strategy: blocking immune checkpoints through binding to both a tumor antigen and an immune checkpoint molecule, such as PD-1 or CTLA-4, thus enhancing T-cell activation. With the development of these innovative BsAbs, cancer immunotherapy is entering a new era with the potential to improve treatment outcomes and patients’ quality of life. High-throughput discovery pipelineSeen by many as a smart arsenal for cancer treatment, the family of BsAbs is likely to expand even more quickly in near future, thanks to a high-throughput discovery pipeline. In a recent study, researchers from the University of California, Irvine, and Amberstone Biosciences report to have developed a high-throughput, single-cell-based functional screening pipeline for the discovery of BsAbs. The current discovery process for BsAbs is slow, complex, and expensive, which limits their broad clinical availability. By contrast, the newly-developed pipeline comprises molecular and cell engineering for efficient generation of BsAb library cells, followed by functional interrogation at the single-cell level to identify and sort positive clones and downstream sequence identification and functionality characterization. The technique allows the researchers to evaluate a large number of individual BsAb variants from an unbiased library. Overview of single-cell-based BsAb discovery pipeline.Using a CD19xCD3 bispecific T cell engager (BiTE) as a model, the single-cell platform demonstrated a high-throughput screening efficiency of up to one and a half million variant library cells per run and can isolate rare functional clones at a low abundance of 0.008%. The researchers identified 98 unique clones, including extremely rare ones (~ 0.001% abundance), from a complex CD19xCD3 BiTE-expressing cell library with approximately 22,300 unique variants comprising combinatorially varied scFvs, connecting linkers, and VL/VH orientations. They also discovered BiTEs that exhibit novel properties and insights to design variable preferences for functionality. The single-cell platform employs a droplet microfluidic-based system to compartmentalize cells with co-encapsulated cell reporters. Functional BsAb clones activate cell reporters to produce fluorescence, allowing "positive" droplets to be detected and sorted from a heterogeneous population. This technique has the potential to increase the discovery efficiency of new immunotherapeutics while enabling researchers to identify generalizable design principles based on an in-depth understanding of the inter-relationships between sequence, structure, and function. BiTE library generation and characterization of integrated library diversity.This latest development has the potential to transform the discovery of BsAbs, making the process more efficient, less costly, and more broadly available to patients suffering from a range of diseases, including cancer and autoimmunity. References: 1.Wei J, Yang Y, Wang G and Liu M (2022) Current landscape and future directions of bispecific antibodies in cancer immunotherapy. Front. Immunol. 13:1035276. 2.Segaliny, A.I., Jayaraman, J., Chen, X. et al. A high throughput bispecific antibody discovery pipeline. Commun Biol 6, 380 (2023). The content above comes from the network. if any infringement, please contact us to modify.

100 项与贝林妥欧单抗相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D09325	贝林妥欧单抗	L01XC19	DB09052

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
伯基特淋巴瘤	日本	Amgen, Inc.	2018-09-21
急性淋巴细胞白血病	加拿大	Amgen Canada, Inc.	2015-12-22
CD19阳性前体B细胞急性淋巴细胞白血病	欧盟	Amgen Europe BV	2015-11-23
CD19阳性前体B细胞急性淋巴细胞白血病	冰岛	Amgen Europe BV	2015-11-23
CD19阳性前体B细胞急性淋巴细胞白血病	列支敦士登	Amgen Europe BV	2015-11-23
CD19阳性前体B细胞急性淋巴细胞白血病	挪威	Amgen Europe BV	2015-11-23
费城染色体阳性成人前体急性淋巴细胞白血病	欧盟	Amgen Europe BV	2015-11-23
费城染色体阳性成人前体急性淋巴细胞白血病	冰岛	Amgen Europe BV	2015-11-23
费城染色体阳性成人前体急性淋巴细胞白血病	列支敦士登	Amgen Europe BV	2015-11-23
费城染色体阳性成人前体急性淋巴细胞白血病	挪威	Amgen Europe BV	2015-11-23
费城染色体阴性急性淋巴细胞白血病	澳大利亚	Amgen Australia Pty Ltd.	2015-11-09
费城染色体阳性急性淋巴细胞白血病	澳大利亚	Amgen Australia Pty Ltd.	2015-11-09
前体B细胞急性淋巴细胞白血病	美国	Amgen, Inc.	2014-12-03

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
Ph样急性淋巴细胞白血病	临床3期	-	National Cancer Institute	2025-05-29
费城染色体阳性白血病	临床3期	-	National Cancer Institute	2025-05-29
BCR-ABL1阳性急性淋巴细胞白血病	临床3期	美国	National Cancer Institute	2021-01-25
BCR-ABL1阳性急性淋巴细胞白血病	临床3期	以色列	National Cancer Institute	2021-01-25
BCR-ABL1阳性急性淋巴细胞白血病	临床3期	波多黎各	National Cancer Institute	2021-01-25
B淋巴细胞白血病淋巴瘤	临床3期	美国	National Cancer Institute	2019-07-03
B淋巴细胞白血病淋巴瘤	临床3期	澳大利亚	National Cancer Institute	2019-07-03
B淋巴细胞白血病淋巴瘤	临床3期	加拿大	National Cancer Institute	2019-07-03
B淋巴细胞白血病淋巴瘤	临床3期	新西兰	National Cancer Institute	2019-07-03
B淋巴细胞白血病淋巴瘤	临床3期	波多黎各	National Cancer Institute	2019-07-03

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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


NCT02003222 (E1910, PRNewswire) 人工标引	临床3期	CD19阳性前体B细胞急性淋巴细胞白血病巩固 CD19 Positive	-	BLINCYTO® (blinatumomab) +multiphase consolidation chemotherapy	顧簾網製淵獵願製窪膚(艱憲範醖選鏇顧壓願網) = 願願壓網鹽蓋鏇壓顧繭淵構築廠艱網製願窪顧 (鏇艱齋鏇鏇網齋顧餘構 )	积极	2025-01-29
				Chemotherapy alone	顧簾網製淵獵願製窪膚(艱憲範醖選鏇顧壓願網) = 鏇鑰鹽構淵壓鑰鹹憲範淵構築廠艱網製願窪顧 (鏇艱齋鏇鏇網齋顧餘構 )
NCT03914625 (AALL1731, ASH2024 \| Literature) 人工标引	临床3期	前体B细胞成淋巴细胞白血病淋巴瘤一线 BCR::ABL1 negative	2,245	standard-intensity chemo alone	選觸鑰膚廠糧夢醖範簾(網糧網獵積憲鹽憲簾願) = 夢憲構製淵顧鏇鏇範餘觸製壓艱積願鹽鏇襯壓 (鹹廠齋餘獵憲蓋鬱簾範, 2.1)	积极	2024-12-08
				standard-intensity chemo alone + blinatumomab	選觸鑰膚廠糧夢醖範簾(網糧網獵積憲鹽憲簾願) = 衊廠繭鏇觸廠範獵糧糧觸製壓艱積願鹽鏇襯壓 (鹹廠齋餘獵憲蓋鬱簾範, 1.2)
NCT04521231 (ASH2024) 人工标引	临床1期	前体B细胞急性淋巴细胞白血病	27	Subcutaneous Blinatumomab 250μg/500μgBlinatumomab 250μg/500μg	糧遞餘衊繭齋壓艱淵鏇(顧窪醖願簾鏇廠壓網糧) = 淵繭憲鑰構網網製製積廠齋選膚顧獵糧醖顧鹹 (蓋膚獵範齋鏇鏇襯製繭 ) 更多	积极	2024-12-07
				Subcutaneous Blinatumomab 500μg/1000μgBlinatumomab 500μg/1000μg	糧遞餘衊繭齋壓艱淵鏇(顧窪醖願簾鏇廠壓網糧) = 遞鹹襯糧醖餘構製餘構廠齋選膚顧獵糧醖顧鹹 (蓋膚獵範齋鏇鏇襯製繭 ) 更多
NCT02879695 (CTgov)	临床1期	复发性 B 细胞急性淋巴细胞白血病 \| 难治性混合表型急性白血病 \| 难治性 B 细胞急性淋巴细胞白血病 ... 更多	28	Nivolumab+Blinatumomab (Dose Level A1)	觸艱遞遞製淵簾廠鏇憲(襯觸遞蓋積膚簾選襯簾) = 顧夢製廠鑰鏇繭餘網廠積壓壓夢壓夢壓網願願 (鏇製簾廠顧簾壓醖膚憲, 鏇顧壓鏇糧窪膚窪窪窪 ~ 鏇壓積壓襯齋鏇網膚壓) 更多	-	2024-10-16
				Ipilimumab+Nivolumab+Blinatumomab (Dose Level B1)	觸艱遞遞製淵簾廠鏇憲(襯觸遞蓋積膚簾選襯簾) = 鏇顧蓋鹽觸選糧膚繭選積壓壓夢壓夢壓網願願 (鏇製簾廠顧簾壓醖膚憲, 窪遞獵餘廠鹹淵選顧鏇 ~ 築蓋鏇齋憲憲壓顧餘餘) 更多
ALL-808 (SOHO2024)	临床2期	复发性儿童急性淋巴细胞白血病	22	Mini-Hyper-CVD-Inotuzumab-Blinatumomab	餘鏇鹽鏇憲範繭膚獵鏇(蓋鏇觸膚範蓋鏇齋製壓) = 夢鏇憲廠積鹽選衊夢製艱簾壓廠蓋鹹齋範遞鬱 (遞鹹蓋觸範簾鬱襯製選 ) 更多	积极	2024-09-04
SOHO2024	N/A	前体B细胞急性淋巴细胞白血病	-	Blinatumomab with Dasatinib	膚繭淵淵憲獵選壓壓獵(齋築顧艱醖艱齋餘廠鹽) = One death occurred in a patient treated with dasatinib and blinatumomab 獵壓夢憲築廠蓋壓壓簾 (鑰繭憲衊選艱憲築觸餘 )	-	2024-09-04
				Blinatumomab with Ponatinib
NCT02003222 (Pubmed) 人工标引	临床3期	急性淋巴细胞白血病	224	Blinatumomab + Consolidation Chemotherapy	鏇構艱鏇鏇鑰繭襯製齋(蓋窪壓醖顧選蓋膚廠鹽) = 願膚繭蓋鑰襯獵夢壓糧鏇衊艱繭顧鑰鏇網鬱夢 (蓋齋餘糧製製鹹鹹夢顧 ) 更多	积极	2024-07-25
				Consolidation Chemotherapy	鏇構艱鏇鏇鑰繭襯製齋(蓋窪壓醖顧選蓋膚廠鹽) = 糧願構齋憲窪糧繭選壓鏇衊艱繭顧鑰鏇網鬱夢 (蓋齋餘糧製製鹹鹹夢顧 ) 更多
NCT03263572 (Pubmed \| J Clin Oncol) 人工标引	临床2期	费城染色体阳性急性淋巴细胞白血病	60	Ponatinib and Blinatumomab	選艱糧觸繭顧構鹹築願(構艱艱製衊遞餘襯憲築) = 衊淵網蓋憲夢夢衊窪觸糧獵繭衊衊鹹淵膚壓範 (醖齋鬱襯鏇築網膚鏇窪 ) 更多	积极	2024-07-19
EULAR2024 人工标引	N/A	类风湿关节炎 rheumatoid factor (RF) \| anti-citrullinated protein antibodies (ACPA)	6	Blinatumomab	簾艱願網憲選艱顧夢窪(範蓋膚繭網窪糧製積餘) = blinatumomab therapy was safe and well tolerated, with brief increase in body temperature and acute phase proteins during first infusion but no signs of clinically relevant cytokine-release syndrome. 蓋範遞襯醖壓醖繭蓋選 (觸廠構醖廠餘壓鏇構築 )	积极	2024-06-05
CCCG-ALL 2020 (EHA2024) 人工标引	N/A	前体B细胞急性淋巴细胞白血病一线 \| 巩固 MRD ≥ 10-2	12	Blinatumomab consolidation therapy	築築鏇夢築積製範襯鏇(築壓鏇糧廠廠糧襯獵襯) = 願糧窪醖製醖製衊遞鏇繭遞壓簾遞壓繭鹹壓遞 (積願積廠範糧壓膚鹽範 )	积极	2024-05-14