This is an open-label phase 2 study of elranatamab in combination with isatuximab administered subcutaneously in patients with relapsed and refractory multiple myeloma (RRMM) who have received at least two prior lines of therapy and who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). The subcutaneous injection method of isatuximab administration, including the device used to administer isatuximab, is investigational.

开始日期2026-08-01

申办/合作机构

The Massachusetts General Hospital

[+2]

NCT06581848

/ Not yet recruitingN/A

Korean Post Marketing Surveillance for ELREXFIO (Elranatamab).

This study is to assess the safety and effectiveness of Elranatamab in the real-world clinical settings for the treatment of patients with multiple myeloma in Korea.

开始日期2025-07-01

申办/合作机构

Pfizer Inc.

NCT06947083

/ Recruiting临床2期IIT

Phase II Study of Elranatamab as Maintenance Therapy Post Ciltacabtagene-autoleucel(Cilta-cel) in Patients With Clinical High Risk Relapsed Myeloma

The purpose of the study is to evaluate the effect of Elranatamab therapy after cilta-cel measuring how long a patient with high risk relapsed myeloma lives without the myeloma getting worse(progressing), also known as progression-free survival (PFS). Patients with clinical high-risk myeloma, defined as having history of myeloma that has grown outside of the bones or having high risk mutations in the myeloma cells, benefit less from cilta-cel compared to myeloma patients without these characteristics.

开始日期2025-06-16

申办/合作机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+1]

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100 项与埃纳妥单抗相关的专利（医药）

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项与埃纳妥单抗相关的文献（医药）

2025-06-01·CLINICAL PHARMACOLOGY & THERAPEUTICS

A Novel Two‐Part Mixture Model for the Incidence and Time Course of Cytokine Release Syndrome After Elranatamab Dosing in Multiple Myeloma Patients

Article

作者: Elmeliegy, Mohamed ; Wang, Diane ; Vandendries, Erik ; Williams, Jason H. ; Irby, Donald ; Poels, Kamrine ; Shtylla, Blerta ; Hibma, Jennifer

Cytokine release syndrome (CRS) is a common, acute adverse event associated with T‐cell redirecting therapies such as bispecific antibodies (BsAbs). The nature of CRS events data makes it challenging to capture an unbiased exposure–response relationship with commonly used models. For example, simple logistic regression models cannot handle traditional time‐varying exposure, and static exposure metrics chosen at early time points and with lower priming doses may underestimate the incidence of CRS. Therefore, more advanced modeling techniques are needed to adequately describe the time course of BsAb‐induced CRS. Herein, we present a two‐part mixture model that describes the population incidence and time course of CRS following various dose‐priming regimens of elranatamab, a humanized BsAb that targets the B‐cell maturation antigen on myeloma cells and CD3 on T cells, where the conditional time‐evolution of CRS was described with a two‐state (i.e., CRS‐yes or no) Markov model. In the first part, increasing elranatamab exposure (maximum elranatamab concentration at first CRS event time (Cmax,event)) was associated with an increased CRS incidence probability. Similarly, in the second part, increased early elranatamab exposure (Cmax,D1) increased the predicted probability of CRS over time, whereas premedication including corticosteroids and IL‐6 pathway inhibitors use demonstrated the opposite effect. This is the first reported application of a Markov model to describe the probability of CRS following BsAb therapy, and it successfully explained differences between different dose‐priming regimens via clinically relevant covariates. This approach may be useful for the future clinical development of BsAbs.

2025-05-01·ANNALS OF PHARMACOTHERAPY

B-Cell Maturation Antigen-Directed Immunotherapies for the Treatment of Relapsed/Refractory Multiple Myeloma: A Review of the Literature and Implications for Clinical Practice

Review

作者: Peery, Matthew R. ; Sharps, Amanda ; Moore, Donald C. ; Hill, Hailey ; Zaver, Aarti

Objective::

To review the pharmacology, efficacy, safety, dosing and administration, and relevance to patient care and clinical practice of B-cell maturation antigen (BCMA) directed immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAb), for the management of relapsed/refractory multiple myeloma (RRMM).

Data Sources::

A literature review of PubMed (1966 to July 2024) was conducted using the keywords idecabtagene vicleucel , ciltacabtagene autoleucel, teclistamab, elranatamab , and multiple myeloma . Data was also obtained from unpublished meeting abstracts and prescribing information.

Study Selection and Data Extraction::

All relevant published articles, unpublished abstracts, and prescribing information on anti-BCMA immunotherapies for the treatment of RRMM were reviewed.

Data Synthesis::

Idecabtagene vicleucel and ciltacabtagene autoleucel are BCMA-directed CAR-T cell therapies that have been compared to standard of care (SOC) regimens for MM in early relapse in the phase III trials KarMMa-3 and CARTITUDE-4, respectively. Both studies demonstrated a significantly improved in response rates, depth of response, and progression-free survival compared to SOC. BsAbs teclistamab and elranatamab have been evaluated in the phase II trials MajesTEC-1 and MagnetisMM-3, respectively. Overall response rates of 63 and 61% were observed with teclistamab and elranatamab, respectively, in a population of patients with heavily pretreated RRMM.

Relevance to Patient Care and Clinical Practice in Comparison with Existing Drugs::

BCMA-directed immunotherapies have demonstrated efficacy in the treatment of RRMM. Safety issues with BCMA-directed immunotherapies include cytokine release syndrome, neurotoxicity, infections, and cytopenias. Operational challenges and issues with access to care exist with these therapies as they may be limited to institutions with the infrastructure to safely administer and monitor patients for toxicities.

Conclusion::

BCMA-directed immunotherapies represent an important advancement in the management of RRMM and have significantly added to the available treatment options for this disease.

2025-05-01·Clinical Lymphoma Myeloma & Leukemia

Comprehensive Review of Bispecific Antibody Constructs In Multiple Myeloma: Affinities, Dosing Strategies and Future Perspectives

Review

作者: Rasche, Leo ; Einsele, Hermann ; Waldschmidt, Johannes M ; Kortüm, K Martin

Despite significant advancements, multiple myeloma (MM) remains incurable, and there is still a pressing need for new therapeutic strategies with highly selective mechanisms of action and balanced off-target toxicity. In recent years, the development of "off-the-shelf" bispecific antibodies (bsAbs) has significantly enhanced our ability to treat relapsed or refractory MM. Teclistamab, elranatamab (both BCMA × CD3), and talquetamab (GPRC5D × CD3) are approved for treating MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Meanwhile, the range of available bsAbs is rapidly expanding, offering patients and healthcare providers a broad selection of options that vary in target antigens, binding domains, construct designs, dosing regimens, and side effects. As linvoseltamab, alnuctamab, and ABBV-383 (all BCMA × CD3), as well as forimtamig (GPRC5D × CD3) and cevostamab (FcRH5 × CD3) progress through late-stage clinical development, emerging trispecific antibodies are now available that target either 2 different MM-associated antigens or provide additional co-stimulatory signals to prevent T-cell exhaustion. Despite this plethora of therapeutic options, resistance to bsAbs is an inevitability, and the optimal positioning of these drugs within the current MM treatment landscape remains to be determined. In this review, we examine the available data on all clinically accessible bsAbs, evaluating their potential, current limitations, and implications for efficacy and safety, with the aim of achieving deeper responses and longer overall survival for MM patients.

239

项与埃纳妥单抗相关的新闻（医药）

2025-05-30

·辉瑞制药

辉瑞在2025年美国临床肿瘤学会年会（ASCO 2025）展现推进癌症诊疗的未来图景

2025年美国临床肿瘤学会年会将于5月30日至6月3日在芝加哥举行，辉瑞公司（NYSE: PFE ）将公布潜在突破性抗肿瘤药物的研发进展。会议期间，辉瑞将展示超过60篇自主研究、研究者发起研究和合作研究的摘要，包括9篇口头报告和6篇快速口头报告，覆盖乳腺癌、泌尿生殖系统肿瘤、血液肿瘤、胸部肿瘤以及结直肠癌等重点癌种。攻克癌症的突破并非一蹴而就。这需要数十年的研究积累、数百万条数据分析，以及全球成千上万名科学家的不懈努力，共同探索可能性。对于生活在癌症阴霾下的患者及其挚爱，这意味着拥有更多与家人相处的时光、规划未来的机会，以及参与生命中重要时刻的可能。在辉瑞，我们不等待突破，我们致力于创造突破。了解我们如何努力改变癌症诊疗的未来。往期 · 推荐辉瑞将在2024年美国临床肿瘤学会年会（ASCO 2024）期间公布多款突破性抗肿瘤药物的研发进展全国肿瘤诊疗规范化提升行动启动会在京召开，夯实高质量肿瘤诊疗体系全国肿瘤防治宣传周 | 科学致胜，共抗泌尿肿瘤靶向免疫疗法易瑞欧®（埃纳妥单抗）首处落地，深度缓解实现多发性骨髓瘤患者“更长生存”

ASCO会议免疫疗法临床结果

2025-05-29

·PRNewswire

John Theurer Cancer Center Presents Innovative Cancer Research at Major Annual Cancer Meeting, Offering New Hope for Patients

Presentations and publications address novel therapeutics, molecular biology studies, and global trends for blood cancers and solid tumors HACKENSACK, N.J., May 29, 2025 /PRNewswire/ -- Investigators from Hackensack Meridian John Theurer Cancer Center (JTCC)—part of the National Cancer Institute-designated Lombardi Comprehensive Cancer Center at Georgetown University—and Hackensack University Medical Center are reporting research findings from 32 studies at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. The meeting is the premier event for cancer professionals and takes place in Chicago from May 30 to June 3. "The future of cancer treatment begins with the pioneering exploration being carried out today," notes Andre Goy, MD, chair, vice president, physician-in-chief of oncology, at Hackensack Meridian John Theurer Cancer Center. "We are fortunate to be in a time where many cancers will respond to standard treatments. But for those cancers that don't, it's critical that patients have access to a world-class research program that will yield innovative therapies. At John Theurer Cancer Center, our globally recognized investigators continue to drive the latest oncology advances in cellular therapy, immunotherapy and other areas, enabling improved outcomes for patients across the Hackensack Meridian Health network and beyond." Several studies address novel drug combinations for multiple myeloma, as well as racial disparities in treatment outcomes and the expression of key biomarkers. Investigators are also presenting data on emerging immunotherapies for leukemia and lymphoma, molecular markers predicting disease relapse, and innovative treatment regimens such as all-oral therapies for acute myeloid leukemia. Solid tumor studies focus on disparities in gastric cancer, machine learning applications for breast cancer metastasis, and promising antibody-drug conjugates for lung cancer. Investigations related to melanoma and skin cancer examine circulating tumor DNA as a marker for disease progression, comparative survival analyses based on biomarkers, and the identification of targetable mutations across different skin cancer types. These findings underscore the breadth of ongoing efforts at John Theurer Cancer Center—New Jersey's largest cancer center—to refine therapeutic strategies, enhance precision oncology, and improve patient outcomes. Multiple Myeloma Research Carfilzomib, iberdomide, and dexamethasone in patients with transplant-eligible newly diagnosed multiple myeloma: Updated results from phase 1/2 study Updated results from phase 2b study of selinexor in combination with carfilzomib, daratumumab, or pomalidomide in patients with multiple myeloma relapsing on current therapy Real-world outcomes of patients with multiple myeloma treated with T-cell engagers compared to those treated on clinical trials Impact of racial disparities on efficacy and safety outcomes for patients with relapsing/refractory multiple myeloma receiving T-cell engagers Heterogeneity in the expression of GPRC5D between patients with multiple myeloma Evaluation of immune checkpoint inhibitors and concurrent radiation therapy for the treatment of extramedullary multiple myeloma Global burden of multiple myeloma: Analysis from 1980 to 2021 Efficacy and safety of less frequent dosing with elranatamab in patients with relapsed or refractory multiple myeloma: A US subgroup analysis from MagnetisMM-3 Leukemia and Lymphoma Peripheral blood cell-free DNA testing as a predictor for relapse post-allogeneic stem cell transplant for acute myeloid leukemia An all-oral regimen of decitabine-cedazuridine plus venetoclax in patients with newly diagnosed acute myeloid leukemia ineligible for intensive induction chemotherapy: Results from a phase 2 cohort of 101 pts Employing novel pan-cancer targets for immunotherapy in leukemias and solid tumors MRD negativity after end of induction in the phase 3 PhALLCON trial: A post hoc analysis Results from the completed dose-finding part of phase 2 study of the innate cell engager acimtamig (AFM13) in combination with AlloNK (AB-101) in relapsed or refractory classical Hodgkin lymphoma (LuminICE-203) Novel analysis of 3-y results from the pivotal EPCORE NHL-1 study: Outcomes in patients with relapsed/refractory large B-cell lymphoma and complete response at 2 years with epcoritamab monotherapy TITANium: An open-label, global multicenter phase 1/2 study of AZD5492, a first-in-class subcutaneous CD8-guided tri-specific T-cell engager, in patients with relapsed or refractory B-cell malignancies Solid Tumor Research Limited changes in the central nervous system immune microenvironment in patients with breast cancer metastasis and capturing these changes using machine learning Relationship between FOLR1 expression and pan-cancer subgroup of tumors with specific transcriptomic profile Disparities and trends in gastric cancer: Incidence, mortality, and stage-specific trends Prevalence of the HPV, EBV, and TTV viral RNA in the plasma of patients with solid and hematologic neoplasms and the detection of a specific immune signature Global trends in soft tissue and extraosseous sarcomas (1980–2021): Regional and economic disparities ZL-1310, a DLL3 antibody-drug conjugate, in patients with extensive stage small cell lung cancer: Phase 1 trial update Ongoing phase 1/2 trial of the hematopoietic progenitor kinase 1 (HPK1) inhibitor NDI-101150 as monotherapy or in combination with pembrolizumab: Clinical safety and efficacy update in clear cell renal cell carcinoma Ipilimumab and nivolumab in patients with metastatic clear cell renal cell carcinoma treated on the phase 3 PDIGREE (Alliance A031704) trial: Results from Step 1 analysis Initial safety and efficacy results from a first-in-human, phase 1/2 study of SAR445877, an anti-PD-1/IL-15 fusion protein, for patients with advanced solid tumors An open-label, phase I trial of the SIRPα monoclonal antibody, BI 770371, alone and in combination with the PD-1 inhibitor ezabenlimab in patients with advanced solid tumors A phase 1 dose escalation and dose expansion study for LNCB74, a B7-H4 targeted antibody drug conjugate, as monotherapy in participants with advanced solid tumors A phase 1, open-label, multi-center study of the safety, tolerability, and efficacy of IPH4502 as a single agent in advanced solid tumors A phase 2 safety and efficacy study of PRT3789 in combination with pembrolizumab in patients with advanced or metastatic solid tumors and a SMARCA4 mutation Phase 3, randomized, placebo-controlled clinical trial of CAN-2409+prodrug in combination with standard of care external beam radiation (EBRT) for newly diagnosed localized prostate cancer Melanoma and Other Skin Cancers Comparison of ctDNA and hematologic ratios as markers of disease progression in early versus late-stage melanoma: A single-center retrospective study Survival analysis based on markers of progression in melanoma: A single-center comparison of survival in patients with high vs low biomarkers Targetable mutations in cutaneous skin cancers: A comparative study across melanoma, squamous cell carcinoma, basal cell carcinoma, and Merkel cell carcinoma SOURCE Hackensack Meridian John Theurer Cancer Center WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 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ASCO会议临床结果免疫疗法临床1期临床2期

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。

抗体药物偶联物申请上市

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KEGG	Wiki	ATC	Drug Bank
D12058	-	-	DB15395

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适应症	国家/地区	公司	日期
多发性骨髓瘤	美国	Pfizer Inc.	2023-08-14

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适应症	最高研发状态	国家/地区	公司	日期
复发性多发性骨髓瘤	临床3期	美国	Pfizer Inc.	2024-02-08
复发性多发性骨髓瘤	临床3期	日本	Pfizer Inc.	2024-02-08
复发性多发性骨髓瘤	临床3期	阿根廷	Pfizer Inc.	2024-02-08
复发性多发性骨髓瘤	临床3期	比利时	Pfizer Inc.	2024-02-08
复发性多发性骨髓瘤	临床3期	巴西	Pfizer Inc.	2024-02-08
复发性多发性骨髓瘤	临床3期	加拿大	Pfizer Inc.	2024-02-08
复发性多发性骨髓瘤	临床3期	捷克	Pfizer Inc.	2024-02-08
复发性多发性骨髓瘤	临床3期	丹麦	Pfizer Inc.	2024-02-08
复发性多发性骨髓瘤	临床3期	芬兰	Pfizer Inc.	2024-02-08
复发性多发性骨髓瘤	临床3期	法国	Pfizer Inc.	2024-02-08

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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


BOSS program (ASCO2025)	N/A	多发性骨髓瘤 LDH \| ferritin \| cytopenia	43	elranatamab (BOSS program)	衊選糧蓋夢鑰膚簾願選(壓鬱膚築構糧獵鏇鹹構) = 築醖鏇願繭製觸顧壓遞顧觸醖襯鹹範壓蓋齋簾 (鑰餘襯餘壓膚繭繭齋鹹 ) 更多	积极	2025-05-30
				elranatamab (iSUD program)	衊選糧蓋夢鑰膚簾願選(壓鬱膚築構糧獵鏇鹹構) = 鑰蓋鹽衊鏇襯蓋鹽醖蓋顧觸醖襯鹹範壓蓋齋簾 (鑰餘襯餘壓膚繭繭齋鹹 ) 更多
NCT04649359 (MagnetisMM-3, ASCO2025)	临床2期	难治性多发性骨髓瘤	47	ELRA 76 mg QW	網網積餘窪襯壓鏇餘顧(鹹窪醖襯選構鹹獵鏇獵) = 100% pts reported any grade treatment-emergent adverse events 壓糧艱簾衊夢選窪構糧 (廠簾壓簾夢窪繭鬱顧衊 ) 更多	积极	2025-05-30
NCT05623020 (MagnetisMM-6, ASCO2025)	临床3期	BCMA-CD3	37	Elranatamab + Daratumumab + Lenalidomide	繭鬱積積積襯獵壓鹹衊(壓簾膚憲餘選製鏇齋壓) = 1 case of G2 ICANS was reported 簾齋願窪網襯窪衊繭鬱 (繭淵窪遞築齋醖廠築淵 ) 更多	积极	2025-05-30
ASH2024 人工标引	N/A	多发性骨髓瘤	-	Teclistamab	鏇繭願淵夢願願鏇積築(窪窪廠遞醖醖淵積醖鬱) = 簾憲製鹹觸觸鬱簾積鏇積鑰蓋製網衊糧壓齋鹹 (構積觸鹽顧鏇襯選夢鬱 ) 更多	积极	2024-12-09
				Elranatamab	鏇繭願淵夢願願鏇積築(窪窪廠遞醖醖淵積醖鬱) = 願糧鹹齋構壓繭餘膚膚積鑰蓋製網衊糧壓齋鹹 (構積觸鹽顧鏇襯選夢鬱 ) 更多
ASH2024 人工标引	N/A	免疫球蛋白轻链淀粉样变性	3	Elranatamab	鬱膚醖製鹽衊夢積網蓋(鹹獵願遞獵簾廠選襯憲) = Two patients developed CRS, and all were grade 2. CRS occurred within 24 hours of the first priming dose, lasted two days, and resolved with IV fluids, tocilizumab, and dexamethasone without recurrence 積憲醖積齋衊鑰餘餘築 (鹽艱積鏇顧築範鹽簾膚 ) 更多	积极	2024-12-08
ASH2024	N/A	复发性多发性骨髓瘤	-	Linvoseltamab	齋願憲積齋範窪窪憲廠(願鹽願衊鑰製鬱齋夢衊) = 淵觸餘壓艱簾鏇築廠淵獵築鑰糧鏇鏇鬱襯襯齋 (蓋廠襯齋夢膚襯構築壓 )	-	2024-12-07
				Teclistamab	齋願憲積齋範窪窪憲廠(願鹽願衊鑰製鬱齋夢衊) = 夢鏇糧夢遞餘顧鹽艱鏇獵築鑰糧鏇鏇鬱襯襯齋 (蓋廠襯齋夢膚襯構築壓 )
NCT04798586 (CTgov)	临床1期	多发性骨髓瘤	4	Elranatamab	顧齋範淵網艱獵夢壓憲 = 願壓糧夢觸鹽壓夢糧憲範願夢顧壓鏇膚遞夢築 (醖製齋淵鬱餘衊鬱築簾, 獵蓋積構構憲衊顧簾積 ~ 淵遞廠夢襯淵鏇遞獵膚) 更多	-	2024-09-27
NCT05228470 (CTgov)	临床1/2期	多发性骨髓瘤 \| 难治性多发性骨髓瘤	39	C1D1+elranatamab (Phase 1b)	衊蓋夢築鬱網鹹蓋淵願 = 鏇襯衊鬱糧築鬱蓋醖鹹簾獵網遞鹽鏇餘觸範醖 (範艱衊觸膚積鬱構顧窪, 繭築築網壓簾繭鹽鑰鬱 ~ 齋艱襯繭鏇醖製願廠壓) 更多	-	2024-09-19
				C1D1+elranatamab (Phase 2)	壓齋淵鹽醖衊鹹壓艱鹽 = 鏇鏇範壓窪顧選鬱構選繭願選餘膚憲壓淵願醖 (繭淵淵醖醖壓繭簾簾窪, 廠製醖築範網顧蓋淵繭 ~ 範夢襯齋夢衊齋範顧餘) 更多
MM-466 (SOHO2024)	N/A	难治性多发性骨髓瘤 BCMA	6	Elranatamab 76 mg QW	製齋範積鬱顧醖積選蓋(窪鏇蓋繭艱壓顧鑰廠鏇) = 構鏇鹹夢醖膚鏇鏇鑰鏇鬱鏇廠艱範鬱壓壓選鬱 (窪構積願鑰鬱鑰積願鑰 ) 更多	积极	2024-09-04
NCT04649359 (MagnetisMM-3, EHA 12024 \| EHA 22024) 人工标引	临床2期	难治性多发性骨髓瘤二线 \| 末线	123	Elranatamab (2-3 prior LOTs)	積膚膚夢艱鹹遞鑰範顧(糧膚蓋糧艱窪餘鹹遞觸) = 艱鬱顧觸壓餘齋顧壓簾廠網願鬱選觸築鬱糧壓 (繭鬱積窪製製觸遞糧願 ) 更多	积极	2024-06-13
				Elranatamab (≥4 prior LOTs)	積膚膚夢艱鹹遞鑰範顧(糧膚蓋糧艱窪餘鹹遞觸) = 齋構構糧積積範鹹膚網廠網願鬱選觸築鬱糧壓 (繭鬱積窪製製觸遞糧願 ) 更多