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2026-01-20

申办/合作机构

National Cancer Institute

NCT06991920

/ Not yet recruitingN/AIIT

Immune-targeted Combination With Acute Lymphoblastic Leukemia-like Chemotherapy for Adult of Acute Leukemia of Ambiguous Lineage: A Prospective, Single-arm, Multicenter Clinical Study

Acute leukemia of ambiguous lineage (ALAL), which refers to acute leukemia without definite evidence indicating cell differentiation along a specific lineage, mainly encompasses two major categories: acute undifferentiated leukemia (AUL) lacking the expression of lineage-specific antigens and mixed phenotype acute leukemia (MPAL) expressing antigens of two or more lineages. Despite certain advancements in basic research on ALAL, there is currently no unified treatment protocol for this disease. The majority of clinical studies are based on retrospective data, lacking prospective cohort studies. In terms of the overall treatment strategy, given the low chemotherapy remission rate, frequent relapses, and poor prognosis of ALAL, it should be treated as high-risk acute leukemia. Patients achieving complete remission should undergo allogeneic hematopoietic stem cell transplantation as soon as possible if conditions permit. Regarding chemotherapy regimens, the current main regimens utilized in clinical practice include ALL-like regimens, AML-like regimens, and hybrid therapies that incorporate both lymphoid and myeloid lineages. Based on existing research, international consensus guidelines recommend ALL-like regimens as the preferred induction treatment option for ALAL patients. In recent years, novel immunotherapy antibody drugs, such as Blinatumomab (a CD19-targeted drug), have achieved remarkable success in the treatment of B-ALL. However, for CD19+ ALAL, there is a lack of effective data regarding whether the first-line application of immunotherapy can further enhance therapeutic efficacy. Simultaneously, the novel small molecule drug venetoclax has demonstrated favorable therapeutic effects on various hematological malignancies. To enhance the overall therapeutic efficacy of adult ALAL in China, based on the above research, we have formulated a comprehensive treatment plan for adult ALAL, integrating Blinatumomab, ALL-like chemotherapy, venetoclax, and TKI drugs into the systemic treatment regimen, and exploring the safety and efficacy of this regimen in the treatment of adult ALAL.

开始日期2025-09-30

申办/合作机构

中国医学科学院血液病医院

NCT06124157

/ Not yet recruiting临床3期IIT

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

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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1,026

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.

2025-08-01·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.

2025-07-01·Nanomedicine-Nanotechnology Biology and Medicine

Two-component T-cell immunotherapy enables antigen pre-targeting to reduce cytokine release without forfeiting efficacy

Article

作者: Gambles, M Tommy ; Kopeček, Jindřich ; Sborov, Douglas ; Stark, Alex ; Spainhower, Kyle ; Li, Jiahui ; Bearss, David ; Kendell, Isaac ; Yang, Jiyuan ; Owen, Shawn

Contemporary T-cell immunotherapies, despite impressive targeting precision, are hindered by aberrant cytokine release and restrictive targeting stoichiometry. We introduce a two-component T-cell immunotherapy targeting B-cell malignancies: Multi-Antigen T-Cell Hybridizers (MATCH). This split antibody technology differs from current therapies by separating cancer cell-targeting components from T cell-engaging components. We demonstrate that this two-component structure facilitates tunable T-cell activation. αCD19 and αCD20 MATCH, administered in two steps, are both compared to the clinical standard bispecific antibody, blinatumomab. In vitro two-dimensional dose analysis and cytokine release data indicate MATCH improves cancer clearance with reduced cytokine release. Cytolytic mechanisms of action are evaluated. αCD20 MATCH anti-cancer efficacy is assayed using a human lymphoma murine model. Decreasing T-cell engager dose 10-fold yields comparable efficacy to non-reduced doses. Ultimately, this split-antibody paradigm may enhance antigen targeting while reducing cytokine release, with such safety and efficacy advantages augmented by the future possibility of multi-antigen targeting with MATCH.

467

项与贝林妥欧单抗相关的新闻（医药）

13 小时之前

·PRNewswire

Miller Children's & Women's Hospital Contributes to Landmark Study Transforming Pediatric Leukemia Treatment

LONG BEACH, Calif., May 29, 2025 /PRNewswire/ -- The Jonathan Jaques Children's Cancer Institute at Miller Children's & Women's Hospital was involved in a pivotal Children's Oncology Group study that has reshaped the standard of care for children with B-cell acute lymphoblastic leukemia. The study, recently published in the New England Journal of Medicine, demonstrated that adding blinatumomab (BLINCYTO®) to chemotherapy significantly improves survival rates in children with B-cell acute lymphoblastic leukemia. Findings from the Children's Oncology Group's Phase III AALL1731 trial, sponsored by the National Cancer Institute's Cancer Therapy Evaluation Program, reveal that children receiving blinatumomab with chemotherapy had a three-year disease-free survival (DFS) rate of 96%, compared to 87.9% for those receiving chemotherapy alone. This marks a significant advancement in pediatric leukemia treatment, with a 61% reduction in the risk of relapse, secondary malignancy, or remission-related death. "The AALL1731 study results are truly practice-changing, further solidifying blinatumomab's role as the standard of care for a large number of children with B-ALL," says Sumit Gupta, M.D., Ph.D., FRCPC, co-chair of the Children's Oncology Group AALL1731 study and oncologist and clinician investigator, Division of Haematology/Oncology at The Hospital for Sick Children (SickKids) and associate professor of pediatrics at the University of Toronto. "These breakthrough data showing a significant improvement in disease-free survival are poised to bring substantial clinical value to children with newly diagnosed B-ALL." The success of the AALL1731 has reshaped treatment protocols world-wide, offering families new hope for improved survival rates and quality of life. "Children's Oncology Group protocols change how we treat children with cancer – this represents a landmark study integrating targeted therapy into standard chemotherapy," says Jacqueline Casillas, M.D., medical director, Jonathan Jaques Children's Cancer Institute, Miller Children's & Women's Hospital. "We are incredibly proud to have contributed to this groundbreaking research, which will help shape the future of pediatric cancer treatment and give more children the chance for long-term remission." Miller Children's & Women's Hospital has a dedicated team of physicians, nurse practitioners, nurses, and research coordinators who ensures rigorous adherence to all study protocols. Together, the hospital's multidisciplinary team consistently offers patients advanced treatment that can ultimately culminate in groundbreaking results like these. "What a privilege it has been to be involved in a Children's Oncology Group's trial that has redefined leukemia treatment," says Maki Okada, MS, CPNP-PC, FNP-BC, nurse practitioner, Miller Children's & Women's Hospital, co-study nurse for Children's Oncology Group AALL1731 study. As research continues to advance, the integration of targeted immunotherapies like blinatumomab is transforming pediatric leukemia care. It builds upon the progress of traditional chemotherapy to further enhance outcomes for young patients. "Over the last decade, BLINCYTO has reshaped the treatment landscape for B-ALL, offering a critical lifeline for thousands of adult and pediatric patients," says Jay Bradner, M.D., executive vice president of Research and Development and chief scientific officer at Amgen. "These powerful new data leave us little doubt about the profound impact of this medicine for a large number of children affected by this disease. We are grateful to the Children's Oncology Group, along with the patients, families, and clinical teams, for their dedication and partnership in advancing this critical study." Miller Children's & Women's Hospital remains dedicated to involvement in pediatric cancer research, actively contributing to studies that shape the future of treatment. As a proud member of the Children's Oncology Group, the hospital is committed to improving survival rates and outcomes for children facing cancer. About Miller Children's & Women's Hospital: Miller Children's & Women's Hospital (millerchildrens.org) is a part of MemorialCare, a not-for-profit, integrated healthcare system. As one of only eight free-standing children's hospitals in California, Miller Children's & Women's is recognized by U.S. News & World Report as a "Best Children's Hospital" for pediatric pulmonology and lung surgery. Regionally, it ranks among the top 10 in the state — treating more than 14,000 children each year — and has become a regional pediatric destination for more than 65,000 children requiring specialized outpatient care through its Cherese Mari Laulhere Children's Village Outpatient Center and satellite centers in Torrance, Fountain Valley, and Irvine. With maternal-fetal medicine specialists and neonatologists available 24/7, Miller Children's & Women's cares for birthing people with high-risk pregnancies and premature infants all under one roof. About The Children's Oncology Group (COG): COG (childrensoncologygroup.org), a member of the NCI National Clinical Trials Network (NCTN), is the world's largest organization devoted exclusively to childhood and adolescent cancer research. COG unites over 10,000 experts in childhood cancer at more than 200 leading children's hospitals, universities, and cancer centers across North America, Australia, New Zealand, and Saudi Arabia in the fight against childhood cancer. Today, more than 80% of the 15,000 children and adolescents diagnosed with cancer each year in the United States are cared for at COG member institutions. Research performed by COG institutions over the past 50 years has transformed childhood cancer from a virtually incurable disease to one with a combined 5-year survival rate of 86%. COG's mission is to improve the cure rate and outcomes for all children with cancer. About Amgen: Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization. For more information, visit Amgen.com. About AALL1731 (NCT03914625): The AALL1731 study was a Phase 3 randomized trial to determine if two non-sequential cycles of BLINCYTO added to chemotherapy improved disease-free survival (DFS) in children with newly diagnosed pediatric National Cancer Institute (NCI) standard risk (SR) B-cell acute lymphoblastic leukemia (B-ALL). The study enrolled 4,264 newly diagnosed NCI SR B-ALL patients, of whom 2,334 were risk stratified at the end of induction therapy as either SR-Average or SR-High. At the first planned interim efficacy analysis (data cutoff June 30, 2024), 1,440 of the eligible and evaluable patients had been randomized. The AALL1731 study was designed and conducted independently from industry. The Cancer Therapy Evaluation Program (CTEP) of the NCI sponsored the trial and provided funding to the Children's Oncology Group to conduct the study. NCI is part of the National Institutes of Health (NIH). In addition, Amgen provided BLINCYTO and support through an NCI Cooperative Research and Development Agreement. SOURCE Miller Children’s & Women’s Hospital WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果临床3期免疫疗法ASCO会议

19 小时之前

·PipelineReview

First patient dosed in YK012 trial-the world's first TCE therapy for primary membranous nephropathy

Key Highlights – Clinical trial to evaluate the safety and efficacy of YK012 in primary membranous nephropathy – Globally, this is the first bispecific CD19-directed CD3 T cell engager immunotherapy for this autoimmune disease – Milder T cell activation than Blincyto and Target cell-dependent T cell activation – Multiple CR cases observed in ongoing r/r NHL Phase Ia trial and r/r ALL Phase Ib/II trial HONG KONG, China I May 29, 2025 I Excyte, a global clinical-stage biotechnology company, announced first patient has been dosed for YK012, the world’s first patient T cell engager that entered into clinical trial for primary membranous nephropathy (pMN). The patient remained well after administration with no adverse reactions witnessed to date. pMN is an autoimmune disease caused by the attack of autoantibodies against podocyte antigens leading to the in situ production of immune complexes. pMN is the most common cause of primary nephrotic syndrome in non-diabetic adults worldwide, accounting for 20% to 37% of affected individuals, and as high as 40% in adults over 60 years of age (1). Currently, 20-30% of pMN cases are resistant to current therapies like rituximab and cyclophosphamide and relapse rates can be high (2). A clear regulatory pathway in this orphan disease in US could make YK012 one of the first approved TCE in the autoimmune space with many other autoimmune and oncology indications to follow. Excyte would file for US investigational new drug (IND) application imminently. The study aims to evaluate the safety, tolerability, and preliminary efficacy of YK012 in PMN patients. Led by Professor Minghui Zhao and Prof Zhao Cui from Peking University First Hospital, the trial is planned to be conducted across multiple centers in China. The clinical trial for this indication in the United States will be collaboratively executed by Excyte and its international partners. “YK012 is a T-cell engaging bispecific antibody targeting both CD19 and CD3, activating T-cell immunity via CD3 while targeting CD19—the most widely expressed tissue-specific marker during B-cell development and thereby enabling B-cell reset. Our data illustrated YK012 mediated significant B cell depletion and have illustrated in current clinical studies extended half-life and limited cytokine release in patients,” said Mr. Andrew Meng, chairman and COO at Excyte. “We look forward to collaborating with regulatory authorities to make YK012 available to this patient population with a high unmet medical need.” In December 2024, YK012 obtained Clinical Trial Approval Notice (No. CXSL2400727) from China’s National Medical Products Administration (NMPA) and was registered on ClinicalTrials.gov (NCT06982729). With the first patient dosed in pMN, Excyte now has a global presence in autoimmune diseases in additional to oncology indications such as NHL and ALL. Earlier this year, Excyte also secured clinical trial approval for systemic lupus erythematosus (SLE), with Professor Xiaofeng Zeng from Peking Union Medical College Hospital serving as Principal Investigator. About Excyte Biopharma Ltd. Excyte Ltd. was co-founded by Dr Qing’an Yuan and Mr Andrew Meng , biotech industry veterans with decades of antibody engineering experiences. The company has also established a U.S.-based wholly-owned subsidiary, Excyte LLC, forming a dual-engine drug R&D hub spanning China and the U.S. Excyte is dedicated to developing innovative bispecific antibody drugs for hematologic cancers, multiple myeloma, solid tumors, autoimmune diseases, and other conditions. Excyte’s FIST platform and next generation assets possess features such as long-acting, low-toxicity, and high-yield technological innovations. For more information, please visit https://www.iExcyte.com/ References: 1.William G Couser, Primary Membranous Nephropathy, Clin J Am Soc Nephrol. 2017 May 26;12(6):983–997. 2.Elham Ahmadian, Seyed Mahdi Hosseiniyan Khatibi, Sepideh Zununi Vahed, Mohammadreza Ardalan, Novel treatment options in rituximab-resistant membranous nephropathy patients, International Immunopharmacology, Volume 107, 2022, 108635, ISSN 1567-5769. SOURCE: Excyte Pharma

免疫疗法临床1期临床申请

2025-05-23

·小药说药

抗体药物40年进化启示录

-01-前言抗体药物是生物医药领域最具革命性的突破之一，凭借高特异性、低毒性和广泛的治疗潜力，已成为全球制药市场增长最快的细分领域。自1986年首个单克隆抗体获批以来，抗体技术历经鼠源、嵌合、人源化到全人源抗体的迭代，逐步解决了免疫原性和疗效问题。目前，抗体药物已覆盖癌症、自身免疫病、感染性疾病等多个领域，市场规模在2021年达到2173亿美元，年增长率约15%。然而，其发展仍面临靶点限制、胞内递送难题、生产工艺复杂等挑战。本文系统梳理抗体药物的发展脉络、作用机制及产业化趋势，以期为行业提供全景视角。-02-治疗性抗体的发展阶段抗体药物的发展可分为四个阶段：鼠源性抗体、嵌合抗体、人源化抗体和全人源抗体。早期鼠源抗体因免疫原性强，易引发人抗鼠抗体（HAMA）反应，临床应用受限。1990年代，嵌合抗体（如抗CD20抗体利妥昔单抗）通过替换人源Fc段减少免疫原性，成为首个成功商业化的治疗性抗体。随后，人源化技术通过仅保留鼠源互补决定区（CDR），进一步优化安全性，代表性药物如曲妥珠单抗。2010年后，全人源抗体（如阿达木单抗）通过噬菌体展示或转基因小鼠技术实现完全人源化，显著降低免疫原性并扩大适应症。目前，全人源抗体已成为主流，但技术壁垒仍高。例如，全人源抗体的亲和力优化和规模化生产仍需突破。此外，新型抗体（如纳米抗体、双抗）的涌现推动技术向更高维度发展。-03-治疗性抗体的作用机制现有抗体药物的常见MOA包括（i）配体-受体相互作用的破坏；（ii）通过抗体依赖性细胞毒性（ADCC）、补体依赖性细胞毒性（CDC）和抗体依赖性细胞吞噬（ADCP）清除靶细胞；（iii）双特异性抗体T细胞结合器；（iv）通过增强内化和降解来下调受体；（v）靶向给药。阻断配体-受体相互作用配体-受体相互作用是许多细胞事件信号转导的初始步骤，包括细胞增殖、粘附和迁移，其中一些与癌症进展有关。结合配体-受体界面两侧的抗体可以破坏结合，干扰信号转导，从而阻止疾病进展。例如，贝伐单抗（Avastin）是2004年开发并批准用于治疗结直肠癌的第一种抗血管生成抗体药物。贝伐单抗的信号阻断抑制血管生成信号，降低肿瘤细胞血供，导致肿瘤缩小。通过ADCC和CDC的细胞清除大部分单克隆抗体的治疗活性源于Fc受体结合区域的效应器功能，这些效应器功能包括ADCC、ADCP和CDC。对于可溶性配体，单克隆抗体结合形成免疫复合物，可被效应细胞消除；对于细胞表面受体，单克隆抗体结合的细胞可被效应细胞攻击，导致细胞破坏和死亡。FDA批准第一个CD20嵌合抗体利妥昔单抗用于治疗非霍奇金淋巴瘤。利妥昔单抗的效力主要来自抗体参与的效应器功能，包括CDC、ADCP和ADCC。双特异性抗体T细胞结合器在许多抗肿瘤效应中，细胞毒性T细胞起着至关重要的作用，然而，抗肿瘤T细胞反应受到癌细胞免疫逃逸机制的限制。以T细胞受体为靶点的单克隆抗体可以模拟抗原识别的效果，诱导特异性T细胞增殖，并释放细胞毒性因子，如IL-2和INF-γ。为了将T细胞导向肿瘤细胞，人们设计了双特异性T细胞接合器。这种双特异性分子一边结合靶肿瘤细胞上过表达的细胞表面抗原，另一边结合T细胞受体中的CD3。从而在肿瘤细胞和T细胞之间架起桥梁，激活T细胞破坏肿瘤细胞。第一个针对CD19和CD3的双特异性T细胞结合器，即blinatumomab，于2014年12月在美国被批准用于治疗急性淋巴细胞白血病（ALL）。通过增强内化和降解实现受体下调尽管人类IgG1可以招募免疫细胞来破坏肿瘤细胞，但是用西妥昔单抗（IgG1）或帕尼妥单抗（IgG2）靶向EGFR，单一疗法的应答率分别仅为11%和8%。对于抗EGFR和HER2，观察到通过抗体结合的非重叠表位协同下调受体酪氨酸激酶，从而更有效地阻断EGFR信号。这种方法可能代表了抗体疗法的一种新策略。靶向给药通过抗体增强靶向给药的方式包括抗体偶联药物（ADC）和抗体免疫脂质体药物（IML）。ADC药物的MOA包括四个步骤：抗体与靶抗原结合、抗原抗体复合物内化、细胞内药物释放，以及有效载荷发挥作用，包括破坏DNA和微管，以及中断DNA合成等。靶向给药的效率取决于抗原抗体复合物的内化和ADC的细胞内分解，这可能受到抗原内吞特性和抗原抗体结合特性的影响。与ADC的情况不同，ADC每个抗体只能携带几个药物分子，每个免疫脂质体封装超过10000个药物分子，允许使用效力较低的化疗药物。此外，与其他ADC相比，免疫脂质体可能具有额外的优势，因为它可以使用相同的靶向颗粒来封装用于治疗的毒性药物和用于肿瘤可视化的放射性同位素。-04-抗体偶联药物(ADC)抗体偶联药物是由靶向特异性抗原的单克隆抗体与小分子细胞毒性药物通过连接子链接而成,兼具传统小分子化疗的强大杀伤效应及抗体药物的肿瘤靶向性。ADCs于20世纪90年代中期首次进入临床试验以来，经过近30年的发展，已经成为一个非常成功的肿瘤学平台。2009年gemtuzumab ozogamicin（Mylotarg) 是FDA批准的第一个ADC药物。目前，全球已上市16款ADC药物。2009年，卡利霉素、金盏花素和美登素类药物是用于ADC开发的主要细胞毒素。十年来，这些分子仍然被用作有效载荷进行优化，以获得更好的稳定性和亲水性。新的细胞毒性物质也被开发出来，如PBDs、杜卡霉素和喜树碱衍生物等。抗体工程在10年间也已经取得了相当大的进展，允许更多的位点特异性偶联，提高了ADC的均一性和稳定性。近年来，ADC在实体瘤和血液瘤中取得突破。例如，DS-8201（靶向HER2）通过可裂解连接子搭载拓扑异构酶抑制剂，显著延长乳腺癌患者生存期。然而，脱靶毒性、耐药性和生产工艺复杂性仍是主要挑战。-05-双特异性抗体单克隆抗体因其特异性靶向分子的能力，已成为癌症治疗中一种关键而有效的治疗方式。然而，由于肿瘤复杂的疾病发病机制，针对单一靶点的单克隆抗体往往不足以表现出足够的治疗效果。因此，针对多个靶点的双特异性抗体（bsAbs）应运而生，它的发展改变了肿瘤免疫治疗的领域。根据其功能机制，BsAb可分为4类：结合同一抗原的两个表位、细胞-细胞接合器、双功能调节剂和细胞治疗中的BsAb。2014年，首个靶向CD19/CD3ε的双特异性T细胞接合器（BiTE）blinatumomab被FDA批准用于治疗急性淋巴细胞白血病（ALL）。自那时起，bsAbs掀起了一阵开发热潮。截至2020年底，有三种bsAbs（catumaxomab、blinatumomab和emicizumab）获得批准。尤其最近几年，3年中新增了11种bsAbs获得了监管机构的批准，其中9种被批准用于治疗癌症(amivantamab, tebentafusp, mosunetuzumab, cadonilimab, teclistamab, glofitamab, epcoritamab, talquetamab, elranatamab) ，2种用于非肿瘤适应症(faricimab, ozoralizumab) 。-06-抗体融合蛋白抗体融合蛋白通过将功能蛋白（如细胞因子、受体）与抗体Fc段结合，延长半衰期并增强效应功能。抗体融合蛋白典型代表包括：依那西普（TNFR-Fc）通过中和炎症因子治疗类风湿关节炎；凝血因子Ⅸ-Fc融合蛋白将半衰期从18小时延长至100小时，减少血友病患者注射频率。此外，细胞因子与抗体或抗体片段的融合可能导致更具针对性的TAA，这可能会提高细胞因子的疗效、药代动力学和局部浓度，并防止全身毒性。该领域的发展重点在于优化融合构象与功能协同性。-07-小分子抗体药物F（ab'）2，是一种分子量为110kDa的二价片段，由两个通过铰链区连接在一起的Fab片段组成。由于尺寸较小，它们比单克隆抗体具有更好的渗透性。NMPA批准了Metuximab-I131，一种放射性碘[131I]标记的抗CD147 F（ab'）2单抗，用于治疗肝癌。目目前，FDA没有批准癌症治疗的F（ab'）2药物。单链抗体由重链（VH）和轻链（VL）的可变区域组成，它们通过柔性肽接头连接在一起。单链抗体可在大肠杆菌中表达，在肿瘤中显示出良好的渗透性。目前，在癌症治疗的临床试验中，正在开发几种单价单链抗体融合蛋白，包括L19-IL-2、rM28、D2C7-IT（I期）和Vicinium（III期）。纳米抗体是在自然界中存在的一些奇特的小分子抗体，它们分子量比较小，可变区即是获得具有抗原结合能力的结构域。FDA和EMA批准的第一种VHH药物caplacizumab（Ablynx Inc），是一种用于治疗成人获得性血栓性血小板减少性紫癜的人源化抗VWF VHH。临床上正在研究各种VHH，以评估其用于不同目的的效果，包括癌症治疗。例如，目前正在评估抗EGFR VHH、抗HER2 VHH、抗VEGFR2 VHH、抗c-Met VHH、和抗CXCR7 VHH。两个VHH正在进行癌症治疗的I期临床试验，Ablynx的抗CXCR4 VHH（ALX-0651）和诺华的新型激动性四价抗DR5 VHH（TAS266）。-08-抗体药物的免疫原性抗药抗体(Anti-drug antibody, ADA)是抗体药物免疫原性评价的主要方式。ADA的形成可以分为与患者相关的因素和与药物相关的因素。患者相关因素包括：1．遗传因素：病人ADA出现和病人当时的免疫状态，主要组织相容性和人类白细胞抗原等位基因的差异相关。2．患者疾病状态：例如有无过往的微生物和病毒感染史；单克隆抗体的免疫原性可能与年龄有关，即儿童的蛋白质周转率与成人不同，这可能导致观察到的免疫原性不同；疾病相关因素也强烈影响免疫原性；先前接触过类似或相关的单克隆抗体也会影响免疫原性。3. 给药方案：重复给药或间歇给药比一次性使用的单克隆抗体诱导免疫原性的可能性更高；如联合使用免疫抑制剂，ADA会降低；与药物相关的因素包括：1.抗体源性：尽管为了降低免疫原性，先后开发了嵌合抗体，人源化抗体和全人源单抗，但是人源化改造，并没有完全消除ADA，即使人源化抗体的CDR区，依然有强的免疫原性，产生抗独特型抗体。2.配方、容器系统、储存条件会影响产品的免疫原性。这些因素可能通过成分与治疗蛋白质和容器封闭系统的相互作用影响免疫原性，例如蛋白质构象的改变、作为免疫佐剂的杂质的提取、引起诸如聚集、微粒或脱酰胺等改变。3.改变的糖基化模式可降低或增强分子的免疫原性，例如通过屏蔽蛋白质主干或通过Toll样受体触发先天免疫应答。4. 非典型的糖基化模式，例如可能发生在全新的表达系统中，与通常使用的表达系统相比，可能引起免疫原性的改变。5.其他有助于免疫原性的因素包括产生方法、途径、剂量和给药频率产生的杂质。-09-抗体药物的产业化趋势抗体药物的开发和发展是高度动态变化的，了解抗体药物的产业化趋势有助于我们发现和设计更具开发潜力的候选药物。基于截至2020年6月批准的89种抗体药物的信息，有82种（92%）是全长的单克隆抗体，有1个是全长IgG的双特异性抗体（emicizumab）。在剩下的六个中，一个是双特异性T细胞结合器（blinatumomab）；三种是抗原结合片段（Fab），包括abciximab, idarucizumab和anibizumab；一种是Fab’（certolizumab pegol）。大多数上市的抗体药物使用的重链亚型是IgG1，占到统计的抗体药物的72.4%，另外分别有12个使用了IgG2重链和IgG4重链。近年来，ADAs发生率较低的抗体得到了更多的批准。1998年获批的曲妥珠单抗成为第一个ADA发生率低于1%的抗体药物。在所有统计的89个抗体药物中，ADA的平均报告发生率为11.3±8.0%；其范围从bezlotoxumab的0%到alemtuzumab的62%。抗体药物的产品形式包括西林瓶、预先填充的注射器或注射笔以及冻干粉。多年来，西林瓶一直是市场上抗体药物最常见的产品形式，占到了55.2%。在其余产品形式中，冻干粉的形式占到22.9%，预填充注射器或注射笔占到21.9%。抗体药物的给药途径包括皮下、静脉注射和其它如皮内、玻璃体内等。在这89种抗体药物中，约三分之二（66.2%）是静脉注射，另有27种（30.4%）是皮下注射。在剩下的三种药物中，分别是皮内（racotumomab）、肌肉内（palvizumab）和玻璃体内（ranibizumab）给药途径。82种全长抗体的半衰期从17小时（sacituzumab goitecan）到50天不等（ravulizumab），平均值为14.5天；大多数上市的抗体药物在15至25天之间被清除。制剂是生物药开发的一个重要方面，对稳定性、安全性、药理学以及给药途径都有重要影响。在89种抗体药物中，87种使用缓冲液，35种使用张力调节剂，60种使用稳定剂，79种使用表面活性剂。-10-结语抗体药物历经四十年发展，已成为现代医学的支柱之一。从单抗到ADC、双抗，技术创新不断拓展治疗边界；从静脉注射到长效制剂，患者依从性持续改善。未来，随着人工智能驱动的抗体设计、新型偶联技术及全球化产能布局的发展将推动抗体药物行业迈向黄金的新纪元。参考文献：1. Emergingnew therapeutic antibody derivatives for cancer treatment. Signal TransductTarget Ther. 2022; 7: 39.2. Antibody–Drug Conjugates: The Last Decade. Pharmaceuticals 2020, 13, 2453. The Chemistry Behind ADCs. Pharmaceuticals (Basel). 2021 May; 14(5): 442.4. Anticancer bispecific antibody R&Dadvances: a study focusing on research trend worldwide and in China. J HematolOncol. 2021; 14: 124.5.Trends in industrialization of biotherapeutics: a survey of product characteristics of 89 antibody-based biotherapeutics. MAbs.2023 Jan-Dec;15(1):2191301.6.Development of Bispecific Antibody for CancerImmunotherapy: Focus on T Cell Engaging Antibody. Immune Netw. 2022 Feb; 22(1): e4.7. A pivotal decade for bispecific antibodies?. MAbs. 2024 Jan-Dec;16(1):2321635.公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

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100 项与贝林妥欧单抗相关的药物交易

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外链

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
复发性 B 细胞急性淋巴细胞白血病	日本	Amgen, Inc.	2018-09-21
难治性 B 细胞急性淋巴细胞白血病	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

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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
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
唐氏综合征	临床3期	美国	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


NCT02811679 (CTgov)	临床2期	难治性惰性非霍奇金淋巴瘤	13	blinatumomab	範網艱構選襯繭衊鏇鬱 = 衊壓觸鑰蓋網衊製鹹襯衊顧衊願願廠積構廠壓 (構積淵壓鹽獵遞獵選繭, 積醖襯範膚醖簾製顧憲 ~ 獵觸範廠築繭憲窪齋艱) 更多	-	2025-05-23
NCT04506086 (CTgov)	临床4期	残留肿瘤 \| 前体B细胞急性淋巴细胞白血病	10	Current Wearable Heatlth Monitoring System (CWHMS)+blinatumomab	蓋壓夢膚製製淵襯餘鹹 = 醖鬱餘壓遞選鏇顧製繭廠憲衊糧獵築夢觸構醖 (夢齋鹽選壓選窪糧醖鑰, 襯構選襯蓋襯醖網艱糧 ~ 壓願鏇衊廠鏇壓鬱襯構) 更多	-	2025-05-18
NCT04556084 (CTgov)	临床2期	CD19阳性B细胞急性淋巴细胞白血病 \| 复发性 B 细胞急性淋巴细胞白血病 \| 胃肠结石 ... 更多	2	blinatumomab	齋艱夢襯範蓋鑰簾願網 = 遞顧鬱蓋願襯衊廠膚醖鹽鏇壓鹽遞廠鬱範艱壓 (網襯選鹹鬱鏇醖鑰製顧, 膚鹽製鑰艱願鑰鏇窪觸 ~ 艱構醖糧糧積鏇糧鏇餘) 更多	-	2025-05-13
NCT03914625 (AALL1731, Pubmed \| N Engl J Med) 人工标引	临床3期	前体B细胞急性淋巴细胞白血病	1,440	Blinatumomab + Chemotherapy	積壓廠積構鹽選衊廠選(鏇壓衊構繭壓觸鑰繭蓋) = 積願壓繭蓋鑰選淵築鏇衊淵範網窪選願範夢築 (願糧淵憲鏇鏇艱觸醖夢, 1.2) 更多	积极	2025-02-27
				Chemotherapy alone	積壓廠積構鹽選衊廠選(鏇壓衊構繭壓觸鑰繭蓋) = 鬱鹹衊膚衊憲遞齋築餘衊淵範網窪選願範夢築 (願糧淵憲鏇鏇艱觸醖夢, 2.1) 更多
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	壓積鏇獵淵齋繭遞選簾(製壓鹽繭鹹範衊壓觸夢) = 積鑰觸簾廠壓窪淵積觸夢製窪糧積鏇簾憲觸築 (窪觸艱構獵網廠顧獵齋 )	积极	2025-01-29
				Chemotherapy alone	壓積鏇獵淵齋繭遞選簾(製壓鹽繭鹹範衊壓觸夢) = 襯遞衊餘鑰窪襯壓鬱齋夢製窪糧積鏇簾憲觸築 (窪觸艱構獵網廠顧獵齋 )
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	廠艱獵醖廠繭構鬱蓋觸(艱顧壓廠構齋繭夢遞壓) = 鹹壓鑰顧壓鑰積衊廠衊糧衊鑰選糧餘壓鏇鑰蓋 (鹹淵淵鑰鏇鑰鹽構窪餘, 2.1)	积极	2024-12-08
				standard-intensity chemo alone + blinatumomab	廠艱獵醖廠繭構鬱蓋觸(艱顧壓廠構齋繭夢遞壓) = 淵構餘獵餘繭網繭夢選糧衊鑰選糧餘壓鏇鑰蓋 (鹹淵淵鑰鏇鑰鹽構窪餘, 1.2)
ASH2024	N/A	CD19阳性B细胞急性淋巴细胞白血病	-	Inotuzumab ozogamicin (InO)	壓鹽顧觸繭觸獵網餘積(衊鏇鹹鏇觸鬱憲襯網構) = 16 (53%) and 2 (7%) developed CRS of any grade and grade 3 to 4, respectively, and 4 (13%) and 1 (3%) developed immune effector cell-associated neurotoxicity syndrome of any grade and grade 3, respectively 膚網膚衊淵選選願積觸 (壓膚獵築範壓蓋蓋製壓 ) 更多	-	2024-12-08
				Blinatumomab (Blina)
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	築餘壓範構製淵淵簾網(鹽願窪憲艱築簾網鹹夢) = 餘襯鹽願鏇顧鹽簾鏇衊製壓獵範構憲觸鏇製鑰 (廠鏇憲淵憲壓窪繭糧簾 ) 更多	积极	2024-12-07
				Subcutaneous Blinatumomab 500μg/1000μgBlinatumomab 500μg/1000μg	築餘壓範構製淵淵簾網(鹽願窪憲艱築簾網鹹夢) = 觸觸鏇鑰選膚網衊獵繭製壓獵範構憲觸鏇製鑰 (廠鏇憲淵憲壓窪繭糧簾 ) 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)	獵鑰範獵網艱遞獵壓襯(齋遞鹽鬱餘夢觸膚願製) = 鑰廠衊遞淵製憲簾蓋衊淵鬱鹹蓋糧艱齋齋淵憲 (窪簾糧夢顧鹽製簾獵憲, 繭鏇鹽衊鬱鬱衊襯襯簾 ~ 窪願選夢構觸餘積積鬱) 更多	-	2024-10-16
				Ipilimumab+Nivolumab+Blinatumomab (Dose Level B1)	獵鑰範獵網艱遞獵壓襯(齋遞鹽鬱餘夢觸膚願製) = 膚鑰餘築衊衊製鹽蓋觸淵鬱鹹蓋糧艱齋齋淵憲 (窪簾糧夢顧鹽製簾獵憲, 糧築憲獵窪築艱製齋艱 ~ 積構壓糧鏇鑰窪築遞範) 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	構壓憲膚獵簾簾構艱夢(繭網淵艱夢艱鹹膚襯鹽) = 顧蓋顧膚衊鹽壓製壓範製憲窪製壓廠廠願廠餘 (鑰繭鏇齋淵觸廠觸獵壓 ) 更多	积极	2024-09-04