更新于：2024-05-03

Loncastuximab tesirine

泰朗妥昔单抗

更新于：2024-05-03

概要

概要

基本信息

药物类型

ADC

别名

Anti-CD19-PBD-conjugate-ADC、Immunoglobulin g1-kappa, anti-(homo sapiens b-lymphocyte antigen cd-19)chimeric monoclonal antibody conjugated to an average of two molecules of tesirine.gamma.1 heavy chain (1-449) (mus musculus vh (ighv1-69*02 (86%) (ighd)-ighj4*01)) (8.8.13) (1-120) -、Lonca

+ [8]

靶点

CD19 x DNA

作用机制

CD19抑制剂(B淋巴细胞抗原CD19抑制剂)、DNA调节剂(DNA调节剂)、DNA烷化剂

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病+ [2]

在研适应症

复发性弥漫性大B细胞淋巴瘤高级别B细胞淋巴瘤难治性弥漫性大B细胞淋巴瘤活化B细胞型+ [15]

非在研适应症

伯基特淋巴瘤纵隔大b细胞淋巴瘤前体B细胞急性淋巴细胞白血病+ [1]

原研机构

ADC Therapeutics SA

在研机构

ADC Therapeutics SA

Swedish Orphan Biovitrum AB

瓴路药业（上海）有限责任公司初创企业

+ [2]

非在研机构-

最高研发阶段批准上市

首次获批日期

美国 (2021-04-23),

B细胞淋巴瘤弥漫性大B细胞淋巴瘤

最高研发阶段(中国)申请上市

特殊审评加速批准 (美国)、附条件批准 (欧盟)

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结构

使用我们的XDC技术数据为新药研发加速。

或

查看完整样例数据

关联

项与泰朗妥昔单抗相关的临床试验

NCT05991388 / Not yet recruiting临床2/3期IIT

A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma

The Glo-BNHL trial is trying to find better medicines for children and young people with B-cell non-Hodgkin Lymphoma (B-NHL) that does not go away (refractory B-NHL) or does but comes back again (relapsed B-NHL). B-NHL is a type of cancer that develops inside or outside of lymph nodes (glands) and organs such as the liver or spleen. Examples of B-NHL are Burkitt Lymphoma and Diffuse Large B Cell Lymphoma, which may be other names used to describe this type of cancer. It is very difficult to cure relapsed or refractory B-NHL. The medicines used now are very powerful with many side effects and only cure around 30 in every 100 children treated. It is very important that investigators quickly find better medicines for these children and young people.
The Glo-BNHL trial will include three groups of children and young people, each given a new medicine (either alone or with chemotherapy). The investigators are looking to make sure the new medicines are safe and that they work to treat the cancer. If the medicine in one group does not work for a child in the trial, then they may be able to join a different group to have another new medicine.
Experts from around the world will carefully pick the medicines most likely to be helpful to be part of the trial. If one of the new medicines seems not to be working as well as hoped then the investigators will take it out of the trial as soon as possible. This will let other new medicines be added to the trial and tested. If a medicine does seem to be working well, then it will continue in the trial to make sure it really is the most useful medicine available.
Children from around the world will be invited to take part in the trial. The investigators will then check on them for at least two years after they finish the trial treatment to look for possible side effects of the new medicine.

开始日期2024-05-01

申办/合作机构

University of Birmingham

[+3]

NCT05672251 / Recruiting临床2期IIT

A Phase 2 Study of Loncastuximab Tesirine Plus Mosunetuzumab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma

This phase II trial studies the safety and how well of loncastuximab tesirine when given together with mosunetuzumab works in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Loncastuximab tesirine is a monoclonal antibody, loncastuximab, linked to a toxic agent called tesirine. Loncastuximab attaches to anti-CD19 cancer cells in a targeted way and delivers tesirine to kill them. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving loncastuximab tesirine with mosunetuzumab may help treat patients with relapsed or refractory diffuse large B-cell lymphoma.

开始日期2024-01-02

申办/合作机构

City of Hope National Medical Center

[+1]

NCT05971251 / Recruiting临床1期IIT

Addition of loNcasTuxImab teSirine to AcalabruTinib in Chronic Lymphocytic Leukemia(Anti-Static Study)

Study is a phase I study to determine the maximum tolerated dose of adding Loncastuximab Tesirine to Aclabrutinib in the treatment of chronic lymphocytic leukemia.

开始日期2023-12-18

申办/合作机构

The University of Alabama at Birmingham

[+1]

100 项与泰朗妥昔单抗相关的临床结果

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100 项与泰朗妥昔单抗相关的转化医学

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100 项与泰朗妥昔单抗相关的专利（医药）

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项与泰朗妥昔单抗相关的文献（医药）

American Journal of Health-System Pharmacy

Loncastuximab tesirine: Risk for dose variance

Article

作者: Kintzel, Polly E

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

2024-01-09·Blood Advances

Clinical outcomes of older and younger patients treated with loncastuximab tesirine in the LOTIS-2 clinical trial

Article

作者: Chen, Lei ; Alderuccio, Juan Pablo ; Xu, Zhiying Cindy ; Caimi, Paolo F ; Solh, Melhem ; Liao, Laura ; Zinzani, Pier Luigi ; Radford, John ; Spira, Alexander ; Kahl, Brad ; Ai, Weiyun ; Stathis, Anastasios ; Wang, Ying ; Ardeshna, Kirit M ; Qin, Yajuan ; Zhou, Xiaolei ; Carlo-Stella, Carmelo ; Hamadani, Mehdi ; Hess, Brian

2024-01-05·Clinical Cancer Research

PET/CT Biomarkers Enable Risk Stratification of Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma Enrolled in the LOTIS-2 Clinical Trial

Article

作者: Ai, Weiyun Z. ; Kahl, Brad S. ; Solh, Melhem ; Radford, John ; Kuker, Russ A. ; Reis, Isildinha M. ; Leslom, Salman ; Alderuccio, Juan Pablo ; Yang, Fei ; Lunning, Matthew A. ; Zinzani, Pier Luigi ; Han, Sunwoo ; Hess, Brian T. ; Stathis, Anastasios ; Carlo-Stella, Carmelo ; Moskowitz, Craig H. ; Ardeshna, Kirit M. ; Lossos, Izidore S. ; Hamadani, Mehdi ; Caimi, Paolo F. ; Nachiappan, Muthiah

Abstract:

Purpose::

Significant progress has occurred in developing quantitative PET/CT biomarkers in diffuse large B-cell lymphoma (DLBCL). Total metabolic tumor volume (MTV) is the most extensively studied, enabling assessment of FDG-avid tumor burden associated with outcomes. However, prior studies evaluated the outcome of cytotoxic chemotherapy or chimeric antigen receptor T-cell therapy without data on recently approved FDA agents. Therefore, we aimed to assess the prognosis of PET/CT biomarkers in patients treated with loncastuximab tesirine.

Experimental Design::

We centrally reviewed screening PET/CT scans of patients with relapsed/refractory DLBCL enrolled in the LOTIS-2 (NCT03589469) study. MTV was obtained by computing individual volumes using the SUV ≥4.0 threshold. Other PET/CT metrics, clinical factors, and the International Metabolic Prognostic Index (IMPI) were evaluated. Logistic regression was used to assess the association between biomarkers and treatment response. Cox regression was used to determine the effect of biomarkers on time-to-event outcomes. We estimated biomarker prediction as continuous and binary variables defined by cutoff points.

Results::

Across 138 patients included in this study, MTV with a cutoff point of 96 mL was the biomarker associated with the highest predictive performance in univariable and multivariable models to predict failure to achieve complete metabolic response (OR, 5.42; P = 0.002), progression-free survival (HR, 2.68; P = 0.002), and overall survival (HR, 3.09; P < 0.0001). IMPI demonstrated an appropriate performance, however, not better than MTV alone.

Conclusions::

Pretreatment MTV demonstrated robust risk stratification, with those patients demonstrating high MTV achieving lower responses and survival to loncastuximab tesirine in relapsed/refractory DLBCL.

241

项与泰朗妥昔单抗相关的新闻（医药）

2024-05-01

·BioSpace

ADC Therapeutics to Host First Quarter 2024 Financial Results and Pipeline Update Conference Call on May 6, 2024

LAUSANNE, Switzerland, May 01, 2024 (GLOBE NEWSWIRE) -- ADC Therapeutics SA (NYSE: ADCT) today announced that it will host a conference call and live webcast on Monday, May 6, 2024 at 8:30 a.m. EDT to report financial results for the first quarter 2024 and provide updates on recent progress against key catalysts from the pipeline. To access the conference call, please register here. Registrants will receive the dial-in number and unique PIN. It is recommended that you join 10 minutes before the event, though you may pre-register at any time. A live webcast of the call will be available under “Events and Presentations” in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call. About ADC Therapeutics ADC Therapeutics (NYSE: ADCT) is a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs). The Company is advancing its proprietary ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors. ADC Therapeutics’ CD19-directed ADC ZYNLONTA (loncastuximab tesirine-lpyl) received accelerated approval by the FDA and conditional approval from the European Commission for the treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in development in combination with other agents and in earlier lines of therapy. In addition to ZYNLONTA, ADC Therapeutics has multiple ADCs in ongoing clinical and preclinical development. ADC Therapeutics is based in Lausanne (Biopôle), Switzerland, and has operations in London and New Jersey. For more information, please visit and follow the Company on LinkedIn. ZYNLONTA® is a registered trademark of ADC Therapeutics SA. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. In some cases you can identify forward-looking statements by terminology such as “may”, “will”, “should”, “would”, “expect”, “intend”, “plan”, “anticipate”, “believe”, “estimate”, “predict”, “potential”, “seem”, “seek”, “future”, “continue”, or “appear” or the negative of these terms or similar expressions, although not all forward-looking statements contain these identifying words. Forward-looking statements are subject to certain risks and uncertainties that can cause actual results to differ materially from those described. Factors that may cause such differences include, but are not limited to: the Company’s ability to achieve the decrease in total operating expenses for 2024 compared to 2022, the expected cash runway into 4Q 2025, the effectiveness of the new commercial go-to-market strategy, competition from new technologies, and the Company’s ability to grow ZYNLONTA® revenue in the United States; Swedish Orphan Biovitrum AB (Sobi®) ability to successfully commercialize ZYNLONTA® in the European Economic Area and market acceptance, adequate reimbursement coverage, and future revenue from the same; approval by the NMPA of the BLA for ZYNLONTA® in China submitted by Overland ADCT BioPharma and future revenue from the same, our strategic partners’, including Mitsubishi Tanabe Pharma Corporation, ability to obtain regulatory approval for ZYNLONTA® in foreign jurisdictions, and the timing and amount of future revenue and payments to us from such partnerships; the impact, if any, from data reported by the University of Miami for their IIT in FL; the timing and results of the Company’s or its partners’ clinical trials including LOTIS 5 and 7, ADCT 601 and 602 as well as the Company’s early-stage pipeline research projects, actions by the FDA or foreign regulatory authorities with respect to the Company’s products or product candidates; projected revenue and expenses; the Company’s indebtedness, including Healthcare Royalty Management and Oaktree and Blue Owl facilities, and the restrictions imposed on the Company’s activities by such indebtedness, the ability to repay such indebtedness and the significant cash required to service such indebtedness; and the Company’s ability to obtain financial and other resources for its research, development, clinical, and commercial activities. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the “Risk Factors” section of the Company's Annual Report on Form 20-F and in the Company's other periodic reports and filings with the Securities and Exchange Commission. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance, achievements or prospects to be materially different from any future results, performance, achievements or prospects expressed in or implied by such forward-looking statements. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this document. The Company undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date of this press release, except as required by law. CONTACTS: Investors and Media Nicole Riley ADC Therapeutics Nicole.Riley@adctherapeutics.com +1 862-926-9040

加速审批上市批准抗体药物偶联物财报

2024-04-25

·PRNewswire

Sobi Q1 2024 report: Strong sales reflecting the strength of the portfolio

STOCKHOLM, April 25, 2024 /PRNewswire/ -- Swedish Orphan Biovitrum AB (publ) (Sobi®) today announced its report for the first quarter 2024 First Quarter 2024 Total revenue increased 19 per cent, 20 per cent at constant exchange rates, (CER)1, to SEK 6,256 M (5,239) Haematology revenue increased 46 per cent at CER to SEK 4,075 M (2,815), reflecting growth in all medicines, mainly driven by strong sales of Doptelet® of SEK 756 M (475), sales of Vonjo® of SEK 320 M (—), and sales of Aspaveli®/Empaveli® of SEK 240 M (95) Immunology revenue decreased 11 per cent at CER to SEK 1,908 M (2,151), mainly reflecting a significant drop in Synagis® sales to SEK 520 M (1,398), partly compensated by strong sales of Gamifant® of SEK 438 M (219), and royalty on Beyfortus™ of SEK 318 M (—) Revenue from medicines in the strategic portfolio more than doubled in the quarter, to SEK 2,193 M (794), driving the majority of the growth. The strategic portfolio grew by 177 per cent at CER and helped to further transform the company The adjusted EBITA margin1,2 was 37 per cent (40), excluding items affecting comparability (IAC)2. EBITA was SEK 2,177 M (2,121), corresponding to a margin of 35 per cent (40). EBIT was SEK 1,313 M (1,495) Earnings per share (EPS) before dilution was SEK 2.35 (3.44)3. Adjusted EPS before dilution1 was SEK 2.70 (3.44)3. Cash flow from operating activities was SEK 2,256 M (1,983) Outlook 2024 - unchanged Revenue is anticipated to grow by a high single-digit percentage at CER The adjusted EBITA margin is anticipated to be in the mid-30s percentage of revenue The strategic portfolio includes Sobi's medicines Aspaveli/Empaveli, Doptelet excluding China, Gamifant, Vonjo and Zynlonta®, and royalty on Sanofi's sales on Altuviiio™ and Beyfortus. Investors, analysts and media are invited to participate in a conference call, which will include a presentation of the results and a Q&A session on the same day at 16:00 CEST. The presentation can be followed live here or afterwards on sobi.com. The slides will be made available on sobi.com prior to the conference call. To participate in the conference call, please use the following dial-in details: Sweden: +46 8 5051 0031 United Kingdom: +44 207 107 06 13 United States: +1 631 570 56 13 For other countries, please find the details here. Sobi Sobi® is a specialised international biopharmaceutical company transforming the lives of people with rare and debilitating diseases. Providing reliable access to innovative medicines in the areas of haematology, immunology and specialty care, Sobi has approximately 1,800 employees across Europe, North America, the Middle East, Asia and Australia. In 2023, revenue amounted to SEK 22.1 billion. Sobi's share (STO: SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com and LinkedIn. Contacts For details on how to contact the Sobi Investor Relations Team, please click here. For Sobi Media contacts, click here. This information is information that Sobi is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out below, on 25 April 2024 at 08:00 CEST. Gerard Tobin Head of Investor Relations This information was brought to you by Cision The following files are available for download:

财报生物类似药

2024-04-24

·生物制品圈

全球上市的ADC药物盘点，看这一篇就够了

20世纪初，Paul Ehrlich首次提出著名的“魔法子弹”理论设想，他认为可以针对病原体特殊的结构特点，寻找和研制只杀伤病原体，不影响正常组织和细胞的药物。随后，抗体-药物偶联的概念被提出，它将单克隆抗体的靶标特异性和细胞毒性分子的抗肿瘤特性结合在一起。历经几十年的尝试，直到2000年靶向CD33的ADC药物Mylotarg（Gemtuzumab Ozogamicin）出现，ADC的发展才取得了实质性的成功。目前全球已有15款ADC药物获批上市，分别是辉瑞的Mylotarg、Besponsa，罗氏的Kadcyla、Polivy，阿斯利康的Lumoxiti、Enhertu，Seagen/武田制药的Adcetris，Seagen/安塞泰来的Padcev，Seagen/Genmab的Tivdak，葛兰素史克的Blenrep，吉利德的Trodelvy，Rakuten Medical的Akalux，ADCTherapeutics的Zynlonta，荣昌生物的爱地希，以及ImmunoGen/华东医药的Elahere。治疗领域涉及淋巴瘤、白血病、乳腺癌、多发性骨髓瘤、乳腺癌、头颈癌、尿路上皮癌等。Mylotarg®（gemtuzumab ozogamicin，吉妥单抗）适应症：急性粒细胞白血病（AML）研发公司：辉瑞靶点：CD33由人源化抗CD33单克隆抗体、卡奇霉素、可切割的连接子组成。抗体与CD33抗原结合后，细胞毒素的内化和释放，从而诱导双链DNA断裂和细胞死亡。全球首款上市的ADC。2000年获FDA加速批准，用于治疗急性粒细胞白血病（AML）。由于由于连接子不稳定、细胞毒素提前释放引起严重毒性反应引发安全性问题，2010年自主撤市。随后，辉瑞补充更新了临床证据（三项临床试验研究：ALFA-0701、AML-19、MyloFrance-1），调整了规格，从原先的5mg/瓶改为4.5 mg/瓶，给药方案也进行了相应调整，推荐剂量从9mg/m2调整为3mg/m2，重新向FDA递交申请。2017年，Mylotarg®获得批准、再次上市，用于用于治疗成人新确诊的髓系细胞分化抗原（CD33）阳性的急性髓系白血病（Acute Myeloid Leukemia，AML），≥2岁儿童和成人的复发难治性髓系细胞分化抗原（CD33）阳性的AML。Adcetris®（brentuximab vedotin，维布妥昔单抗，安适利®）适应症：霍杰金淋巴瘤\系统性间变性大细胞淋巴瘤研发公司：武田和Seattle Genetics靶点：CD30一种靶向CD30的ADC，由嵌合lgG1抗体cAC10、 MMAE和蛋白酶可切割的连接子组成。内化后，蛋白水解释放MMAE，MMAE通过破坏微管系统诱导细胞周期阻滞和凋亡。由于MMAE具有旁观者效应，BV在表达CD30的组织异质性肿瘤中也有效。2011年8月被FDA批准。用于治疗霍奇金淋巴瘤（HL）和间变性大细胞淋巴瘤（sALCL）。在我国于2020年5月被NMPA批准，用于治疗复发或难治性sALCL和CD30阳性HL患者，是第二款国内获批上市的ADC。2021年获欧盟批准，可作为CD30表达的sALCL一线治疗药物，也成为全球第一个用于一线治疗的ADC。Brentuximab vedotin是第二代ADC代表药物，采用人鼠嵌合抗体、或人源化单抗代替鼠源单抗，即降低了免疫原性，又增强了肿瘤靶向性，并且采用的连接子也更加的稳定。其缺点是裸抗较多，这些未结合的单抗与偶联物竞争抗原结合位点，影响疗效。过高的药物/抗体比率（DAR），引起抗体聚集，清除加快，非特异性毒性增加等。Brentuximab平均携带4个MMAE分子，其药物/抗体比率（DAR）为4，分子量约153kDa。Kadcyla®（ado-trastuzumab emtansine，恩美曲妥珠单抗，赫赛莱®）适应症：乳腺癌研发公司：罗氏和ImmunoGen靶点：HER2一种靶向Her2的ADC，由人源化抗Her2 IgG1单抗（曲妥珠单抗）、小分子细胞毒素DM1和不可切割的连接子组成。在体循环和肿瘤微环境中能维持较高的稳定性。2013年2月22日，FDA批准Kadcyla®用于曾接受曲妥珠单抗和紫杉烷治疗的转移性Her2阳性乳腺癌患者治疗。2019年5月3日，FDA批准Kadcyla®作为单一药物用于接受新辅助曲妥珠单抗治疗后残留疾病的Her2阳性乳腺癌患者的辅助治疗。2020年1月，NMPA批准Kadcyla®用于接受了紫杉烷类联合曲妥珠单抗为基础的新辅助治疗后，仍残存侵袭性病灶的HER2阳性早期乳腺癌患者、不可切除局部晚期或转移性乳腺癌患者的辅助治疗。是我国首个上市的抗体药物偶联物（ADC），也是全球首款被批准用于实体瘤的ADC。Kadcyla®是商业化最成功的ADC。2021年全球ADC市场规模超过52亿美元，其中Kadcyla®独占半壁江山，销售额达到21.7亿美元。Kadcyla平均每个抗体上连接3.5个DM1，分子量约148,781Da。Besponsa®（inotuzumab ozogamicin，奥加伊妥珠单抗，贝博萨®）适应症：BCP-ALL研发公司：辉瑞靶点：CD22一种人源化抗CD22单克隆抗体，通过酸不稳定的腙连接子与卡奇霉素偶联。CD22是一种内吞受体，是B细胞急性淋巴细胞白血病(ALL)的特异性标志物，在90%以上的B细胞恶性肿瘤患者中表达。一旦ADC与CD22受体结合，该复合物被内化到靶细胞内，触发卡奇霉素的释放，卡奇霉素通过与DNA双螺旋的小沟结合并引起位点特异性双链DNA切割，从而诱导细胞凋亡。2017年6月获得EMA批准上市，用于治疗患有复发或难治性前体B细胞急性淋巴细胞性白血病（ALL）的成人患者。2017年8月获得美国FDA批准，治疗成人复发或难治性B细胞前体急性淋巴性白血病。这是首款获得FDA批准的靶向CD22的抗体偶联药物。2021年12月在我国上市，成为中国第四款上市的ADC。NMPA的批准基于境外临床试验B1931022数据在中国的递交，豁免中国注册临床试验。上市后，需开展上市后研究（B1931034）。Besponsa®作为辉瑞的第二款ADC、第三代ADC产品，抗体免疫原性更低，靶向性更强，细胞活性更高，连接子更稳定，小分子毒性药物的稳定性和亲水性有了进一步改善，ADC的稳定性、均一性也更好。Besponsa分子量约为160kDa，与每个抗体平均结合的6个卡奇霉素，分布范围为2~8。Lumoxiti®(Moxetumomab pasudotox，帕西妥莫单抗)适应症：复发性或难治性毛细胞白血病（HCL）的成年患者研发公司：阿斯利康靶点：CD22由抗CD22单克隆抗体共价连接到假单胞菌外毒素a(PE38)的38kDa片段上。免疫毒素的Fv部分与CD22结合，内化后，通过催化延伸因子-2(EF-2)中二苯二胺残基的ADP核糖基化诱导凋亡。2018年9月获得FDA批准上市，用于治疗复发性或难治性毛细胞白血病(HCL)成人患者。2021年2月，获EMA批准。但五个月后，同年7月EMA发布公告，撤销了它在欧盟的上市许可。然而由于临床使用非常低，阿斯利康在2023年7月将Lumoxiti永久撤出美国市场。两个撤市均为商业考量，并非安全性问题。Polivy®（polatuzumab vedotin，泊洛妥珠单抗，优罗华®）适应症：弥漫性大B细胞淋巴瘤研发公司：罗氏靶点：CD79b一种由抗CD79b单克隆抗体、蛋白酶可切割的连接子和MMAE偶联。CD79b是B细胞特异性表面蛋白，它在超过90%的B细胞非霍奇金淋巴瘤中高表达，例如：弥漫性大B细胞淋巴瘤、滤泡性淋巴瘤等，CD79b与抗体结合后被迅速内吞并递送至溶酶体内。因此，CD79b成为治疗这类淋巴瘤的理想靶点。2019年6月11日首次获得FDA加速批准上市，联合苯达莫司汀和利妥昔单抗，用于治疗至少两次以上的复发或难治性（R/R）弥漫性大B细胞淋巴瘤（DLBCL）的成年患者。随后，于2021年1月和3月，分别在欧盟、日本批准上市。2023年1月，Polivy®获得中国国家药品监督管理局（NMPA）正式批准。适应症为：联合利妥昔单抗、环磷酰胺、多柔比星和泼尼松适用于治疗既往未经治疗的弥漫性大B细胞淋巴瘤（DLBCL）成人患者；以及联合苯达莫司汀和利妥昔单抗用于不适合接受造血干细胞移植的复发或难治性弥漫性大B细胞淋巴瘤成人患者。Polivy®是20多年来国内唯一获批用于 DLBCL 一线治疗的创新靶向药物。与传统治疗方案相比，Polivy®可显著改善患者的临床结局，是20年来首个显著改善复发或难治性弥漫性大B细胞淋巴瘤的新治疗方案。因此，在美国、欧盟和日本，Polivy®被授予“孤儿药资格”，在美国还被FDA授予“突破性药物资格”，欧盟EMA则被授予“优先药物资格”。Polivy®药物/抗体比率（DAR）为3-4，分子量约150kDa。Enhertu®(fam-trastuzumab deruxtecan-nxki，德喜曲妥珠单抗，优赫得®）适应症：胃食管交界处癌，转移性胃癌，转移性乳腺癌研发公司：阿斯利康；第一三制药靶点：HER2Enhertu®是第三代ADC的代表，由靶向Her2的曲妥珠单抗、可切割的四肽连接子和细胞毒性拓扑异构酶I抑制剂组成。研究表明T-DXd对Her2高或低表达的肿瘤细胞或Her2突变的肿瘤细胞都有效，其原因可能包括：1）T-DXd的DAR值高达8，因此具有高效的有效载荷；2）释放的有效载荷具有较高的膜透性，使其能够进入邻近的肿瘤细胞，产生旁观者效应；3）新型基于四肽的连接子在血浆中具有很高的稳定性。2019年12月，Enhertu获得FDA加速批准，用于既往接受过HER2治疗的、不可切除，或转移性HER2阳性乳腺癌成年患者。2022年3月正式递交国内上市申请，并于5月被正式纳入优先审评目录，首个适应症为：治疗既往接受过一种或一种以上抗HER2药物治疗的不可切除或转移性HER2阳性成人乳腺癌患者。Enhertu®在治疗HER2阳性转移性乳腺癌等方面表现出的惊人疗效，是ADC药物研发近年来罕见的重大进展，也令HER2成为目前热度最高的ADC药物靶点。Enhertu®是全球首个且目前唯一在HER2阳性晚期乳腺癌二线治疗中，头对头对比的ADC药物，并取得了阳性结果。据Natrue子刊市场预测，Enhertu有望在2026年达到62亿美元的销售额，占据全球40%的ADC市场份额。或将取代Kadcyla，成为新一代的ADC “药王”。Padcev®（enfortumab vedotin，恩诺单抗）适应症：尿路上皮癌研发公司：Seagen；安斯泰来靶点：Nectin-4一种靶向nectin-4的ADC，由一种靶向nectin-4的人单克隆抗体、蛋白酶可切割的连接子、MMAE偶联。Nectin-4是一种细胞粘附分子，在97%的尿路上皮癌中过表达，并与肿瘤生长和增殖有关。Nectin-4在成人健康组织中表达量很低，但在多种肿瘤细胞中高表达，如：在尿路上皮癌、膀胱癌、乳腺癌、卵巢癌、胃癌、肝细胞癌和胰腺癌等组织中，具有特异性的高表达，与肿瘤的发生和转移具有密切的关系，可通过激活PI3K/AKT途径促进肿瘤细胞增殖、分化、迁移、侵袭等。因此，Nectin-4已成为许多实体瘤诊断和治疗的重要靶点。2019年12月，FDA加速批准了Padcev®用于局部晚期或转移性尿路上皮癌的成年患者，这些患者先前接受过程序性死亡受体-1(PD-1)抑制剂或程序性死亡配体受体-1(PD-L1)抑制剂以及含铂化疗药物的治疗。Padcev®是首个获批治疗尿路上皮癌的ADC，也是首个以Nectin-4为靶点的获批药物Trodelvy®（sacituzumab govitecan，戈沙妥珠单抗，拓达维®）适应症：三阴性乳腺癌研发公司：吉利德靶点：Trop-2一种靶向Trop-2的单抗，通过酸不稳定的腙可切割连接子与SN-38偶联组成。SN-38是一种拓扑异构酶-1抑制剂，是化疗药物伊立替康的活性代谢物。给药后，ADC与肿瘤细胞上的Trop-2结合，并促使SN-38释放，引发DNA损伤，随后导致细胞周期阻滞。由于SN-38的膜透性，它可以在不被内化的情况下刺激附近细胞的抗肿瘤作用，发挥旁观者效应。TROP-2，一种跨膜糖蛋白，它在乳腺癌、胃癌、非小细胞肺癌、小细胞肺癌、结肠癌、胰腺癌等多种肿瘤组织中过表达，尤其是三阴乳腺癌，表达率高达90%以上。2020年4月，Trodelvy®获得FDA加速批准用于对既往接受过两种或两种以上转移性疾病治疗的成人转移性三阴性乳腺癌的治疗。2022年6月，NMPA批准Trodelvy®用于既往至少接受过2种系统治疗，其中至少一种治疗针对转移性疾病的不可切除的局部晚期或转移性三阴乳腺癌成人患者。Blenrep®（belantamab mafodotin，玛贝妥单抗）适应症：多发性骨髓瘤研发公司：GSK靶点：BCMA一种靶向B细胞成熟抗原(BCMA)的lgG抗体，通过不可切割的马来酰亚胺基己酰(MC)连接子与MMAF偶联。BCMA是一种在恶性浆细胞上大量表达的细胞表面蛋白，是治疗多发性骨髓瘤的一个很重要的靶点。一旦belantamab maodotin与BCMA结合，该复合物内化并在溶酶体中降解，MMAF释放，诱导生长阻滞和细胞凋亡。2020年8月，FDA加速批准Blenrep®用于复发或难治性多发性骨髓瘤的成人患者，这些患者之前接受过至少四种治疗，其必须包括抗CD38单克隆抗体、免疫调节剂和蛋白酶体抑制剂。2022年11月，Blenrep®的验证性临床III期DREAMM-3试验宣告失败，这是一项“头对头”的优效性试验，研究对比了Blenrep单药与泊马度胺联合低剂量地塞米松（PomDex）的疗效。同年12月，Blenrep®撤出美国市场，也成为FDA“加速批准”来，最快退市的药物。然而，这不代表GSK停止了这款药物的开发，DREAMM系列的临床研究没有暂停，GSK正通过联合用药寻找其他获益可能。Akalux®（Cetuximab Sarotalocan Sodium，沙西妥昔单抗）适应症：头颈癌研发公司：Rakuten靶点：EGFR由靶向EGFR的抗体cetuximab与光敏物质IR700偶联而成。2020年9月，获得日本厚生劳动省正式批准，用于治疗手术无法切除的头颈部恶性肿瘤，也是全球首个光免疫疗法ADC，治疗时需要与BioBlade激光系统联合使用。Akalux®与癌细胞表面的EGFR抗体结合后，利用近红外线照射肿瘤病灶，红外线可以局部激活偶联染料并破坏已经与化学物质结合的肿瘤细胞膜，从而达到灭杀癌细胞的目的。Zynlonta®（Loncastuximab tesirine，朗妥昔单抗）适应症：LBCB研发公司：ADCTherapeutics靶点：CD19一种靶向CD19的抗体，通过可切割的酶型连接子与细胞毒性烷基化剂SG3199偶联而成。SG3199是一种合成的PBD二聚体，通过促进DNA链间交联的形成阻止细胞分裂，具有强大的细胞毒性作用。2021年4月23日，Zynlonta®获得FDA加速批准，用于弥漫性大B细胞淋巴瘤(DLBCL)患者。2022 年 12 月，Zynlonta®得到欧洲药品管理局（EMA）的附条件批准。并且CDE 官网显示，2023年7月，瓴路药业注射用泰朗妥昔单抗申报上市（受理号：JXSS2300057）。这也是国内首款申报上市的 CD19 ADC。爱地希®（Disitamab Vedotin，维迪西妥单抗）适应症：胃癌，尿路上皮癌研发公司：荣昌靶点：HER2由亲和力更高的新型人源化抗HER2抗体、可裂解连接子和微管抑制剂MMAE组成，作用机制包括抑制HER2信号通路和MMAE的细胞毒性。2021年6月和2021年12月，爱地希®获NMPA批准上市，适用于至少接受过2种系统化疗的HER2过表达局部晚期或转移性胃癌（包括胃食管结合部腺癌）患者的治疗，以及2+或3+的局部晚期或转移性尿路上皮癌的治疗。爱地希®为首家获批上市的国产ADC品种。除已获批2项适应症外，荣昌生物还开展了多项针对实体瘤的临床研究，包括乳腺癌（BC），同时还在探索对于其他HER2过表达的常见癌种的治疗，如非小细胞肺癌（NSCLC）、胆道癌（BTC）、黑色素瘤等。Tivdak®（tisotumab vedotin-tftv，替索单抗）适应症：宫颈癌研发公司：Genmab靶点：TF一种靶向组织因子(TF-011)的单克隆抗体、一种可切割的mc-VC-PABC连接子和MMAE组成。研究显示，相对正常宫颈组织，TF在宫颈癌组织中大量表达。一旦vedotin与TF结合，MMAE就会被传递到细胞中，从而阻断微管蛋白聚合并终止细胞分裂。2021年9月，美国FDA授予Tivdak加速批准，用于化疗期间或化疗后疾病进展的复发性或转移性宫颈癌成人患者。Tivdak®是首个获批用于治疗化疗期间或化疗后疾病进展的复发性或转移性宫颈癌患者的ADC。Elahere（mirvetuximab soravtansine-gynx，索米妥昔单抗）适应症：卵巢癌研发公司：ImmunoGen、华东医药靶点：FEα一款FRα靶向ADC，由IgG1亚型抗FRα人源化单抗M9346A、抗微管蛋白剂DM4（一种美登素衍生物）和连接子三部分组成。FRɑ在72%-100%的间皮瘤、35%-68%的三阴性乳腺癌、76%-89%的卵巢癌和14%-74%的非小细胞肺癌患者样本中高表达2022年11月获FDA作为一种单药疗法加速批准，用于治疗先前已接受过1-3种全身治疗方案、FRα阳性、铂耐药的上皮性卵巢癌、输卵管癌、原发性腹膜癌成人患者。结语以上就是全球上市的15款ADC药物，从原研地区来看，尽管其中只有爱地希®来自中国，确能说明中国创新药企不再是门外汉、看客，而是参与者和座上宾。虽然全球生物医药行业的寒冬还未结束，许多在原始创新道路上坚持的中国企业依旧踽踽独行。不过，最艰难的时刻已经过去，属于中国原创新药的春天已悄然来临。资料来源：1.BiG生物创新社：上市ADC系列2.全球已批准上市的15款ADC药物的包装外观图.抗体圈.2024-04-13.盘点：国内已上市ADC&双抗全景图.药渡.2023-08-174.已获批上市的ADC药物的开发回顾及未来展望.生物药搬运工.2024-04-115.2023年终盘点：ADC药物推进肿瘤治疗进程飞跃！全球上市的ADC药物概览来了.咚咚癌友圈.2023-12-236.国内上市的ADC药物(抗体药物偶联物)汇总盘点.利多卡vivi.2024-02-26识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

抗体药物偶联物上市批准临床结果多肽偶联药物

100 项与泰朗妥昔单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11338	-	L01XC	DB16222

研发状态

适应症	最高研发状态	国家/地区	公司
弥漫性大B细胞淋巴瘤	批准上市	美国更多	ADC Therapeutics SA 更多
复发性弥漫性大B细胞淋巴瘤	批准上市	欧盟更多	Swedish Orphan Biovitrum AB 更多
难治性弥漫性大 B 细胞淋巴瘤	临床3期	波多黎各更多	ADC Therapeutics SA 更多
复发性滤泡性淋巴瘤	临床2期	美国更多	University of Washington 更多
难治性滤泡性淋巴瘤	临床2期	美国更多	University of Washington 更多

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03589469 (LOTIS-2, Pubmed)	临床2期	弥漫性大B细胞淋巴瘤 CD19	145	Loncastuximab tesirine	觸淵獵齋獵構獵鏇鑰築(窪願壓壓繭廠願鬱積壓) = 醖範遞淵艱廠醖蓋獵獵築淵廠繭窪衊獵淵憲襯 (夢積積壓膚築獵簾鹽鹹, 50.0 ~ 81.0) 更多	-	2024-04-01
NCT03684694 (CTgov)	临床1/2期	弥漫性大B细胞淋巴瘤 \| 套细胞淋巴瘤	136	Ibrutinib+Loncastuximab Tesirine (Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib)	獵顧積窪齋繭襯窪網膚(壓齋餘製憲繭淵窪鬱襯) = 夢艱遞選壓製選衊壓鹹壓壓艱糧鑰蓋範築積鑰 (齋構鹽遞選襯蓋淵衊淵, 蓋鏇願鑰製襯廠淵淵繭 ~ 鹽淵顧壓網壓衊窪襯膚) 更多	-	2024-02-06
NCT03684694 (CTgov)	临床1/2期	弥漫性大B细胞淋巴瘤 \| 套细胞淋巴瘤	136	Ibrutinib+Loncastuximab Tesirine (Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib)	獵顧積窪齋繭襯窪網膚(壓齋餘製憲繭淵窪鬱襯) = 鏇積醖壓鹹壓顧壓鑰壓壓壓艱糧鑰蓋範築積鑰 (齋構鹽遞選襯蓋淵衊淵, 衊淵顧鬱糧範醖築夢壓 ~ 廠顧觸衊齋膚壓壓窪範) 更多	-	2024-02-06
GlobeNewswire 人工标引	N/A	滤泡性淋巴瘤	-	ZYNLONTA + rituximab	廠選鬱積製鬱繭醖鑰顧(簾窪廠淵鑰襯餘襯網構) = 顧廠積膚選壓壓製淵憲壓簾鬱夢網簾鏇觸繭遞 (夢鏇範膚醖製積膚積繭 ) 更多	积极	2024-01-04
LOTIS-7 (GlobeNewswire) 人工标引	临床1期	滤泡性淋巴瘤 \| 弥漫性大B细胞淋巴瘤 \| 边缘区B细胞淋巴瘤	-	mosunetuzumab or glofitamab+ZYNLONTA	築願鏇鹹鬱鏇餘選糧淵(夢繭構膚簾繭鑰夢構襯) = The dose-limiting toxicity (DLT) period has been cleared for the first dosing level of ZYNLONTA 90 µg/kg in both arms, 範夢選膚醖願憲範鑰遞 (鹽淵鬱夢廠製壓膚網糧 )	积极	2024-01-04
ChiCTR2300072058 (ASH2023) 人工标引	临床2期	弥漫性大B细胞淋巴瘤	64	Loncastuximab Tesirine	獵鏇簾憲鬱蓋築蓋築膚(繭簾觸鹽鏇壓遞鏇繭選) = 網鬱獵製積鑰襯淵鏇願網鏇壓鹹餘鹽淵簾鏇醖 (選糧遞願願蓋構繭鑰糧, 38.7 ~ 64.2) 更多	积极	2023-12-11
ASH2023	临床2期	难治性滤泡性淋巴瘤	-	Loncastuximab tesirine + Rituximab	鏇夢鑰觸憲艱夢壓鑰製(鏇蓋鹹鑰願簾齋淵遞獵) = 壓積廠憲範廠衊遞鹹範遞築壓積壓餘遞襯窪衊 (範鏇衊醖築膚壓衊廠餘 ) 更多	-	2023-12-11
NCT03589469 (LOTIS-2, ASH2023)	临床2期	复发性弥漫性大B细胞淋巴瘤	33	Loncastuximab tesirine	築艱憲廠觸觸構蓋鹽遞(鑰鏇鏇糧觸範鑰糧壓顧) = 憲鑰網餘憲範夢淵憲淵醖衊願淵鹹餘膚糧廠觸 (蓋廠膚窪遞艱觸鹹簾鏇 )	-	2023-12-10
NCT05464719 (ASH2023)	临床2期	弥漫性大B细胞淋巴瘤巩固	30	Loncastuximab Tesirine	襯衊簾觸鏇蓋夢醖壓積(觸膚鑰範構壓鏇鑰獵醖) = 鏇壓鏇鹽獵鹹築遞鏇鹽鹽築窪鬱繭憲積製鏇構 (膚襯範衊齋獵糧廠艱醖 ) 更多	-	2023-12-10
NCT04699461 (CTgov)	临床2期	难治性滤泡性淋巴瘤 \| 复发性滤泡性淋巴瘤	6	Loncastuximab Tesirine (Loncastuximab Tesirine)	顧顧獵顧網膚遞鹽觸憲(窪簾鹽廠膚鏇艱簾衊艱) = 鑰鑰選鏇選糧窪襯觸網觸獵淵衊鑰簾築膚壓窪 (鹽鏇齋糧淵積壓築襯夢, 壓積製積選顧淵鑰製鹹 ~ 膚齋蓋艱餘糧範構繭繭) 更多	-	2023-10-23
NCT04699461 (CTgov)	临床2期	难治性滤泡性淋巴瘤 \| 复发性滤泡性淋巴瘤	6	Idelalisib (Idelalisib)	顧顧獵顧網膚遞鹽觸憲(窪簾鹽廠膚鏇艱簾衊艱) = 衊廠憲範製遞窪膚獵鹹觸獵淵衊鑰簾築膚壓窪 (鹽鏇齋糧淵積壓築襯夢, 範醖鬱鏇廠簾築願鬱製 ~ 廠構憲淵獵醖衊壓壓鹽) 更多	-	2023-10-23
NCT03589469 (LOTIS-2, EHA2023)	临床2期	难治性弥漫性大 B 细胞淋巴瘤 \| 复发性弥漫性大B细胞淋巴瘤	145	Loncastuximab tesirine	繭網衊餘艱繭繭餘齋鏇(獵淵襯鑰鏇選夢繭齋憲) = 淵鏇廠遞膚鏇鬱顧壓襯窪糧鑰選願簾遞製糧夢 (繭窪製餘鏇鹹窪蓋網觸 ) 更多	-	2023-06-08