The primary goal of this study is to establish the safety of chronic Convection Enhanced Delivery (CED) of the chemotherapeutic drug Topotecan for patients with recurrent malignant glioma that harbors the Isocitrate Dehydrogenase mutation (IDH-mut). The secondary goal of the study is to study drug distribution and assess the tumor response to prolonged continuous CED of Topotecan.
Convection Enhanced Delivery is a novel method of drug delivery that allows administration of a drug directly to the brain. In CED, a drug pump is placed under the skin in the chest or abdominal region. The pump is connected to a catheter that is tunneled underneath the skin to the brain. The tip of the catheter then infuses Topotecan directly onto the brain tumor. There will be a total of four treatment infusions over the course of 23-29 days, with a 5-7-day rest period between each infusion. Throughout this period, patients' health will be monitored through imaging, blood draws, and regular exams. At the end of the treatment period, the pump will be removed, followed by resection of the tumor. Patients will be followed for the duration of their lives.
This is the investigator's second clinical trial studying CED of TPT in recurrent glioma. In the prior Phase 1b trial, chronic pulsatile CED safely and effectively delivered Topotecan to patients with IDH mutant recurrent Glioblastoma (WHO grade 4).

开始日期2025-10-04

申办/合作机构

Columbia University

NCT06647953 / Not yet recruiting临床3期IIT

Prospective Treatment of Types I, II and III Pleuropulmonary Blastoma (PPB)

This phase III trial tests how well surgery plus chemotherapy compared to surgery alone works in treating patients with type I pleuropulmonary blastoma (PPB), and tests how well surgery plus standard chemotherapy with the addition of topotecan works compared to surgery plus standard chemotherapy alone in treating patients with type II and III PPB.
Historically, most children with type I PPB had surgery and approximately 40% of children with type I PPB received chemotherapy following their surgery, usually for 22-42 weeks. There has not been a consistent standard for which children with type I PPB receive chemotherapy after surgery. For patients whose tumor has been removed completely with surgery, observation without chemotherapy may work as well as giving chemotherapy after surgery in preventing a return of the PPB tumor.
The standard chemotherapy for patients with types II or III PPB in the United States is four cycles of IVADo (ifosfamide, vincristine, dactinomycin, and doxorubicin) followed by 8 cycles of IVA (ifosfamide, vincristine and dactinomycin). Ifosfamide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of tumor cells in the body. Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only used in cancer chemotherapy (antineoplastic antibiotic). It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill tumor cells. It also blocks a certain enzyme needed for cell division and DNA repair. Topotecan is in a class of medications called topoisomerase I inhibitors. It works by interfering with tumor cell DNA which kills them. Giving topotecan in addition to standard IVADo and IVA chemotherapy regimens may shrink the cancer as well as or better than the standard therapy or could decrease the chance the tumor spreads while causing fewer side effects.

开始日期2025-03-17

申办/合作机构

The Children's Oncology Group Foundation, Inc.

NCT06425419 / Not yet recruiting临床1期IIT

The Safety and Efficacy of Intravitreal Topotecan for the Treatment of Proliferative Vitreoretinopathy

The goal of this clinical trial is to evaluate the safety and efficacy of intravitreal topotecan for the treatment of patients with rhegmatogenous retinal detachment due to proliferative vitreoretinopathy (PVR) or resulting from an open globe injury, and compare the outcomes to those who do no receive intravitreal topotecan. The main objectives it aims to achieve are:
* to study the safety profile of intravitreal topotecan in the treatment of PVR
* to evaluate the efficacy of intravitreal topotecan in treating PVR.
Post-consent, participants will:
* undergo vitrectomy (with or without scleral buckle) as part of standard treatment for retinal detachment.
* receive intravitreal topotecan at the time of surgery, post-operative day 7 and post-operative day 28 (if randomized to receive the medication)
* come in at post-operative day 1, 7, 28, 56, 84, 126 and 168 to undergo a complete ophthalmic exam along with a fundus photography and optical coherence tomography of the macula, have their intraocular pressure and visual acuity measured and their adverse events monitored, if any.
Researchers will compare participants who receive intravitreal topotecan for PVR to those who do not to see if there is a significant variability in recurrence of retinal detachment, rate of retinal reattachment and PVR grade 6 months after surgery.

开始日期2025-01-01

申办/合作机构

Massachusetts Eye & Ear Infirmary, Inc.

100 项与盐酸托泊替康相关的临床结果

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100 项与盐酸托泊替康相关的转化医学

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100 项与盐酸托泊替康相关的专利（医药）

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3,305

项与盐酸托泊替康相关的文献（医药）

2025-02-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Structure-activity relationship study of novel evodiamine amino acid conjugates with potent anti-colorectal cancer efficacy

Article

作者: Hu, Zecheng ; Jiang, Weifan ; Wang, Zhen ; Peng, Xue ; Zhuo, Linsheng ; Xiong, Yongxia ; An, Zhigang ; Zhang, Siyi ; Lei, Zhengwen ; Chen, Shuting ; Mo, Hanxuan ; Wei, Xiuzhen ; Wu, Junbo ; Zhang, Xi ; Peng, Ying

Evodiamine has been a promising lead structure with broad-spectrum antitumor activity. Druggability optimization is the most challenging part of evodiamine-based lead-to-candidate campaign. Amino acids as building blocks for conjugates are widely incorporated into approved drug and drug candidates, demonstrating highly attractive druggability. Herein, a series of evodiamine amino acid conjugates were designed and synthesized based on the evodiamine lead compound (±)-8b discovered in our previous work. The structure-activity relationship (SAR) studies culminated in the identification of a promising conjugate (-)-15h featuring a N-Boc-l-glutamine group and a chiral carbon atom (sinister), which exhibited nanomolar antiproliferative activity against LoVo and RKO colorectal cancer cells. Moreover, (-)-15h could inhibit topoisomerases I, arrest the cell cycle in the G2/M phase, and induce apoptosis. Importantly, (-)-15h (tumor growth inhibition rate was 82.53 % in 40 mpk) showed better efficacy and tolerability to that of parent compound (-)-8b (tumor growth inhibition rate was 51.22 % in 40 mpk) in LoVo xenograft model. Further, (-)-15h (tumor growth inhibition rate was 70.09 % in 40 mpk) showed comparable efficacy and better tolerability to that of topotecan (tumor growth inhibition rate was 70.67 % in 0.5 mpk) in HT-29 xenograft model. Collectively, this study further provided a strong scientific basis for amino acid-based structural modifications and a drug lead for anti-colorectal cancer applications.

2025-01-01·RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES

HIGH-DOSE INTRAVITREAL TOPOTECAN FOR RECURRENT RETINOBLASTOMA, SUBRETINAL SEEDS, AND VITREOUS SEEDS

Article

作者: Valdes-Perez, Nicole ; Lally, Sara E ; Medina, Robert ; Shields, Carol L ; Burak Acar, Ahmet ; Shields, Jerry A ; Evans, Haley ; Bansal, Rolika

Purpose::

To evaluate the efficacy and safety of high-dose intravitreal topotecan (IvitTopo) for recurrent retinoblastoma.

Methods::

There were 13 patients with recurrent retinoblastoma treated with high-dose IvitTopo (90 micrograms [μg]/0.18cc–100 µg/0.20cc). The primary outcome measures were tumor control, globe salvage, and treatment complications.

Results::

At date first seen, median patient age was 9 months, and the affected eye was classified as International Classification of Retinoblastoma Group B (n = 2, 15%), Group C (n = 3, 23%), or Group D (n = 8, 62%) retinoblastoma with initial therapy of intravenous chemotherapy (n = 9, 69%) or intraarterial chemotherapy (n = 4, 31%). Recurrent tumor was detected at median 10 months as solid tumor (n = 3), subretinal seeds (n = 10), and/or vitreous seeds (n = 3) and high-dose IvitTopo (median three injections) delivered at monthly intervals. Additional chemotherapy was delivered by intraarterial (n = 8, 62%) or intravenous (n = 1, 8%) routes, and one eye received additional cryotherapy (n = 1, 8%). In three cases (23%), there was no additional therapy. At mean follow-up of 9 months, regression of solid tumor, subretinal seeds, and vitreous seeds was achieved in 12 cases (92%), and globe salvage was achieved in all cases (n = 13, 100%). Of those three eyes treated with high-dose IvitTopo alone, tumor control was initially achieved in all cases (100%), but one case that previously demonstrated massive vitreous seeding showed late recurrence of a solitary vitreous seed at 8 months. There were no complications.

Conclusion::

High-dose IvitTopo is an effective and safe therapy for recurrent retinoblastoma, in conjunction with other therapy, and possibly as a stand-alone therapy.

2025-01-01·AMERICAN JOURNAL OF OPHTHALMOLOGY

Single- Versus Triple-Agent Intra-Arterial Chemotherapy for Retinoblastoma

Article

作者: Aldhawi, Abeer ; Feng, Zhao Xun ; Zaarour, Christian ; Kletke, Stephanie N ; Gallie, Brenda L ; Alshahrani, Najah O ; Muthusami, Prakash ; Parra-Farinas, Carmen ; Chau, Kelvin ; Mallipatna, Ashwin ; Alshahrani, Najah O. ; Kletke, Stephanie N. ; Shaikh, Furqan ; Gallie, Brenda L.

PURPOSE:

To compare the ocular and systemic outcomes of single- (melphalan) versus triple-agent (melphalan, topotecan, carboplatin) intra-arterial chemotherapy (IAC) for retinoblastoma (RB) eye salvage.

DESIGN:

Retrospective single-institutional clinical cohort study.

METHODS:

Children <18 years with RB who underwent one or more IAC procedures between 2016 and 2024 with minimum 6-month follow-up were reviewed. Data included clinical features, IAC procedural details, additional eye-saving treatments, complications, and follow-up. Primary outcomes included ocular and systemic complications of IAC, intraocular recurrence, extraocular extension, metastasis, and death. Secondary outcomes were tumor response, ocular survival, and recurrence-free ocular survival. Comparative analysis was performed for single- versus triple-agent groups. A SWIMMER^rb plot graphically illustrated additional treatments following IAC.

RESULTS:

Thirty-eight eyes of 37 children (24 unilateral RB) were reviewed. Two eyes (2 children) had single- followed by multi-agent IAC and were excluded. Of 35 included children, one had bilateral triple-agent IAC. IAC (median, 3 doses; range, 1-4) was employed as primary (n = 21 eyes) or secondary (n = 15 eyes) treatment. Chemotherapy was single-agent in 13 eyes and triple-agent in 23 eyes. Following IAC, 25 eyes required additional eye-saving treatments (69% single- v 70% triple-agent, P = .983). At final follow-up, the triple-agent group was more likely to achieve very good partial or complete tumor response (91% v 62%, P = .030). Two-year recurrence-free ocular survival was 63.3% (95% CI 45.7-80.9), similar for both groups (P = .700). Globe salvage was 72%. Two-year ocular survival was 72.2% (95% CI 57.2-87.2), higher for the triple-agent group (82.6% v 53.8%; P = .059). Ocular complications occurred in 31% of eyes in the single- and 52% of eyes in the triple-agent group (P = .215). The rate of systemic complications was 38% versus 74% in the single- versus triple-agent groups, respectively (P = .036). No extraocular extension, metastasis, or death were observed at median 34.2 months (range, 14.5-87.0) follow-up.

CONCLUSIONS:

Triple-agent IAC was associated with improved RB tumor response and ocular survival, though similar recurrence-free ocular survival compared to single-agent. While there were more complications with triple-agent IAC, most were mild or transient.

249

项与盐酸托泊替康相关的新闻（医药）

2024-12-16

·翰森制药

翰森制药HS-20093（B7-H3 ADC）获欧洲药品管理局(EMA)优先药物（PRIME）认定

- HS-20093 (GSK'227)获PRIME认定，用于复发广泛期小细胞肺癌（ES-SCLC）患者的治疗 - PRIME认定旨在授予具有解决重大未满足医疗需求潜力的药物 - 广泛期小细胞肺癌与高复发率、治疗手段有限及预后不良息息相关 2024年12月16日，翰森制药集团有限公司（以下简称“翰森制药”，03692.HK），中国领先的创新驱动型制药企业宣布，合作方葛兰素史克（GSK）就GSK5764227 (GSK'227,亦称HS-20093)获得欧洲药品管理局 (EMA) 优先药物（PRIME）认定。该药物为B7-H3靶向抗体药物偶联物（ADC），正在评估用于复发广泛期小细胞肺癌（ES-SCLC）患者的治疗。 EMA的PRIME认定得到了ARTEMIS-001研究初步临床数据的支持。这是一项由翰森制药进行的、针对200多名患者的正在进行的Ⅰ期开放标签多中心试验，评估局部晚期或转移性实体瘤（包括复发性ES-SCLC）的安全性、耐受性和初步抗肿瘤活性。该试验的有效性和安全性结果在今年9月举行的2024年世界肺癌大会（WCLC）上公布。近期，GSK开始了一项全球Ⅰ期临床试验，以支持GSK'227的注册性研究。 2024年8月，美国食品药品监督管理局（FDA）授予GSK'227突破性疗法认定，用于含铂化疗期间或之后进展的（复发或难治性）广泛期小细胞肺癌（ES-SCLC）患者治疗。2024年11月，中国国家药品监督管理局（NMPA）将HS-20093纳入突破性治疗药物，拟定适应症为经标准一线治疗（含铂双药化疗联合免疫）后进展的广泛期小细胞肺癌（ES-SCLC）。关于HS-20093 HS-20093(GSK'227)是一种新型B7-H3靶向抗体药物偶联物(ADC)，由全人源抗B7-H3单抗与拓扑异构酶抑制剂(TOPOi)有效载荷共价连接而成，目前正在中国开展用于治疗肺癌、肉瘤、头颈癌以及其他实体瘤的多项I期、II期及III期临床研究。 2023年12月20日，翰森制药与GSK 订立独家许可协议，授予GSK全球独占许可（不含中国内地、香港、澳门及台湾），以开发、生产及商业化HS-20093(GSK'227)。关于肺癌肺癌是全球癌症相关发病率和死亡率的主要原因。1 在欧洲，2022年估计有484,554例新发病例和375,784例因肺癌死亡的患者。2小细胞肺癌（SCLC）占所有肺癌病例的10-15%，是其中最致命的亚型之一。3,4广泛期小细胞肺癌（ES-SCLC）在诊断时约占所有SCLC病例的60%—85%，其特征为肿瘤已扩散至肺外。5铂类耐药或难治性患者通常预后极差，中位总生存时间不足六个月。6,7 关于优先药物（PRIME）认定 2016年3月，欧洲药品管理局(EMA)推出了优先药物（PRIME）计划，旨在加速医药短缺领域重点药品的审评进程，尽早使患者受益。该计划支持开发一些很有潜力帮助到患者及针对严重未满足的医疗需求的药品。该计划也为药物研发人员提供了与EMA早期沟通和增强互动的渠道，从而加速药物开发。关于翰森制药翰森制药是中国领先的创新驱动型制药企业，下属豪森药业、常州恒邦药业、翰森生物医药等子公司，重点关注抗肿瘤、抗感染、中枢神经系统、代谢及自身免疫等重大疾病治疗领域，致力于通过持续创新提高人类生命质量。截至2024上半年，公司已上市7款创新药，创新产品营收占比达77.4%。公司连续多年位居全球制药企业百强、中国医药研发产品线最佳工业企业前3强，是国家重点高新技术企业、国家技术创新示范企业。公司于2019年6月在香港联交所挂牌上市（股票代码：03692.HK）。更多信息请访问：https://cn.hspharm.com/。参考文献： 1.Leiter A, Veluswamy RR, Wisnivesky JP. The global burden of lung cancer: current status and future trends. Nat Rev Clin Oncol. 2023;20(9):624-639. 2.Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263. 3.Rudin CM, Brambilla E, Faivre-Finn C, et al. Small-cell lung cancer. Nat Rev Dis Primers. 2021;7(1):3. 4.Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and thepath forward. Nat Rev Cancer. 2017 Dec;17(12):725-737. Doi: 10.1038/nrc.2017.87. Epub 2017 Oct Erratum in: Nat Rev Cancer. 2017;17(12):765. 5.Porte M, Vaudron A, Crequit P, Vaugier L, Chatellier T, Fronteau C, Raimbourg J, Goronflot T, Bennouna J, Pons-Tostivint E. A Multicenter Study Assessing the Real-World Use and Effectiveness of First-Line Chemotherapy Plus Immunotherapy in Advanced Small-Cell Lung Cancer (SCLC) Patients. Clin Lung Cancer. 2024 Mar;25(2):e101-e111.e2. doi: 10.1016/j.cllc.2023.11.009. Epub 2023 Nov 23. PMID: 38072729. 6.Trigo J, Subbiah V, Besse B, Moreno V, López R, Sala MA, Peters S, Ponce S, Fernández C, Alfaro V, Gómez J, Kahatt C, Zeaiter A, Zaman K, Boni V, Arrondeau J, Martínez M, Delord JP, Awada A, Kristeleit R, Olmedo ME, Wannesson L, Valdivia J, Rubio MJ, Anton A, Sarantopoulos J, Chawla SP, Mosquera-Martinez J, D'Arcangelo M, Santoro A, Villalobos VM, Sands J, Paz-Ares L. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020 May;21(5):645-654. doi: 10.1016/S1470-2045(20)30068-1. Epub 2020 Mar 27. Erratum in: Lancet Oncol. 2020 Dec;21(12):e553. doi: 10.1016/S1470-2045(20)30676-8. PMID: 32224306. 7.Topotecan USP. Available at:https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022453s002lbl.pdf. Accessed 13 Nov 2024 声明：1、翰森制药不推荐任何未获批药品使用或未获批适应症用药。 2、本新闻稿中的医疗信息仅供信息和新闻报道使用，不用于广告目的，不要将其用于医疗保健或诊断建议。前瞻性说明本新闻稿旨在提供关于翰森制药集团有限公司及其附属公司（包括其子公司，统称为“翰森制药”）的信息。它不构成对翰森制药或任何投资建议的信息披露。本新闻稿包含的信息可能包括与翰森制药业务和产品前景、计划、信念、预期和策略相关的前瞻性声明。这些声明是基于推测性假设的预测，并不保证未来的表现。它们受到诸如科学、商业、政治、经济、财务、法律因素以及竞争环境和社会条件等风险和不确定性的影响，这些因素很多都是翰森制药无法控制且难以预测的，因此实际结果可能与此处所述有显著差异，且过去的证券价格趋势不应作为未来行情的指导。因此，投资者在使用这些信息进行投资决策时应谨慎行事。“致力于”“预期”“相信”“预测”“意图”“预计”“可能”“将”“应该”“计划”“继续”“目标”“考虑”“估计”“指导”“潜在”“追求”以及于任何未来计划、行动或事件的讨论中使用的类似词语和术语，均表示前瞻性声明。翰森制药不承诺或保证前瞻性信息的准确性、及时性或完整性，并且不承担更新或修订这些前瞻性声明的义务。无论是翰森制药还是其任何董事、员工或代理人，均不对任何证明不准确或无法实现的前瞻性声明负责，也不对因依赖本新闻稿中提供的信息而产生的任何损失或损害负责，包括但不限于直接、偶然、间接或惩罚性的损害。本新闻稿中的所有信息均为发布之日的最新信息。翰森制药不承担因新发展、未来事件或其他情况而更新或修订这些信息的责任，除非法律要求。此外，翰森制药保留在任何时候未经通知对本新闻稿的全部或部分内容进行更改、更正或中断的权利。对于特别与上市公司有关的信息，公司鼓励投资者参考翰森制药（03692.HK）的公告和财务报告。 END

突破性疗法抗体药物偶联物临床3期临床结果临床1期

2024-12-10

·癌度

治疗小细胞肺癌的抗体偶联药ABBV-011，首次人体临床试验结果公布了！

小细胞肺癌属于肺癌的一种亚型，是一种高度侵袭性的恶性肿瘤，占到肺癌的15%左右。小细胞肺癌的特点是增殖速度快，早期就容易发生广泛转移，75%以上的小细胞肺癌确诊时就属于广泛期小细胞肺癌，没有手术治疗的机会，预后也比较差，5年生存比例仅为6.8%。局限期小细胞肺癌则是可以同步放化疗，中位无进展生存时间为13.5个月，5年病情无进展的比例为25%。大多数广泛期小细胞肺癌的标准一线治疗是铂类与依托泊苷，联合PD-L1抑制剂。二线治疗则是拓扑替康和鲁比奈克汀，小细胞肺癌的三线治疗目前还没很好的办法。而且尽管一线治疗有很多小细胞肺癌患者的病灶缩小，但是大多数患者会复发，中位无进展生存时间仅为5.1个月。二线治疗的中位无进展生存时间为3.5个月。 SEZ6在小细胞肺癌表达比较高，所以就成了一个潜在的治疗靶点。ABBV-011就是针对SEZ6的抗体偶联药，在临床前的研究里，ABBV-011展现出比较好的抗肿瘤活性。下面就是这款药的一期临床试验结果，癌度为大家做一下编译，希望对大家有所帮助。参考文献刊例示意图 1、ABBV-011治疗小细胞肺癌展现治疗活力通过对入组患者的肿瘤组织样本进行免疫组化检测，找到SEZ6阳性的患者（大于25%的肿瘤细胞染色强度大于1）。截止2022年8月，有99名患者接受了ABBV-011单药治疗，入组小细胞肺癌患者每3周注射一次ABBV-011，这些患者的中位年龄为63岁，32%的患者之前接受过大于一种治疗，41%的患者之前接受过2种以上的治疗，26%的患者之前接受过大于3种以上的治疗。临床治疗的缓解率研究结果表明，总体的治疗缓解率为25%，也就是25%的患者肿瘤病灶缩小超过30%，中位缓解持续时间为4.2个月，中位无进展生存时间为3.5个月。最常见的治疗引起的不良事件是疲劳 (50%)、恶心 (42%) 和血小板减少 (41%)。最常见的肝脏治疗引起的不良事件是天冬氨酸氨基转移酶升高 (22%)、γ-谷氨酰转移酶升高 (21%) 和高胆红素血症 (17%)。 2、更新一步的临床研究，期待获批小细胞肺癌的相关药物我们写了很多，但相比非小细胞肺癌的治疗效果和生存期，小细胞肺癌的治疗仍然有很长的路要走。抗体偶联药在很多类型的肿瘤治疗里获得了进展，小细胞肺癌缺乏好的靶点，ABBV-011针对SEZ6这个靶点的研究数据给出了一些思路。而且这款药的一期临床试验探索出了最佳剂量，每3周一个治疗周期，每次治疗以每公斤体重1毫克剂量则耐受性良好，对复发的小细胞肺癌展现出不错的抗肿瘤活性。大家可以关注这款药，积极申请这款药的二期临床试验，争取免费使用药物的机会。欢迎大家关注癌度，了解全球肿瘤诊疗的最新进展。癌度与吉因加启动的“基因检测人人可及”计划里，仅需要3000元就能检测36个基因，大家可以联系癌度或扫描上面的二维码咨询癌度医学顾问，了解基因检测的相关问题。参考文献： Daniel Morgensztern et al, A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6–Targeting Antibody–Drug Conjugate, in Patients with Small Cell Lung Cancer. Clinical Trials: Targeted Therapy, 2024. 往期推荐双特异性抗体药泽妥珠单抗获批，用于治疗非小细胞肺癌和胰腺癌! 新型HER2卡替疗法，当所有HER2药物无效了还有可能参加这种药物的临床试验！再说“肠道菌群”，回答了为什么乳腺癌药物对某些人更有效！再说ALK的三代靶向药，初次靶向治疗或靶向药耐药后用洛拉替尼分别能有多长的生存期？

临床2期临床结果

2024-12-09

·生物制品圈

ADC行业 | 偶联药物行业现状与发展趋势

抗体偶联药物(Antibody-Drug Conjugates，ADCs)作为现阶段最活跃的创新药赛道之一，通过将细胞毒药物连接到靶向肿瘤的抗体上，实现了靶向药物和化疗药物的结合，进而实现高精度治疗。 ADC药物市场规模全球ADC药物市场处于快速发展阶段，市场份额相对分散。但随着市场的逐步成熟和竞争格局的形成，行业领先企业的市场份额将逐渐扩大。未来几年，全球ADC药物市场规模将持续增长，2028年预估达到260亿美元。预估全球ADC药物市场份额，将由2021年占据抗体药物市场的3%，增长至2030年占比14%。根据沙利文数据，2023年多款ADC药物销售突破10亿美元，Enhertu优势领先，稳坐ADC药物畅销首位，2024年的销售额预估将达到35亿美金。 Padcev尿路上皮癌的市场份额快速增长中，吉利德ADC药物针对二线治疗三阴乳腺癌及HR+/HER2-乳腺癌持续放量。 2023年全球ADC销售额统计全球ADC药物市场规模及预测近几年来，ADC药物市场规模逐年高速增长，年增长率保持在30%以上，2023年首次突破百亿美元规模。 2024年上半年,全球ADC药物市场规模为63.55亿美元,预计全年将超过130亿美元。国内ADC 药物市场看了全球ADC药物市场，再看国内市场，中国的ADC药物市场份额上升空间更大，有望从2021年的1%上升至2030年的14%。 2022年，中国抗体偶联药物销售额达到8.15亿元，仅占我国抗肿瘤药物销售总额的0.53%。ADC 药物赫赛莱获批后，中国的ADC 药物市场开始步入快速增长期。近几年，中国 ADC 药物市场将迎来爆发式增长，预计由 2022 年的人民币 8 亿元增长至 2030 年的人民币 662 亿元。 ADC 药物作为精准靶向药物，未来可替代部分化疗药物市场（约 1400 亿元）。技术迭代 ADC技术发展历经4个阶段，第一代代表：Mylotarg、Besponsa；第二代ADC药物代表Kadcyla、Adcetris等；第三代ADC代表Enhertu、Besponsa、Padcev,第四代的ADC代表为Trodelvy和SKB264. 第一代ADC药物第一代的ADC药物抗体多采用鼠源或嵌合人源化抗体，连接子不稳定，毒副作用较大。载药的毒性较低，且是随机偶联，药物效力不足。第二代ADC药物第二代的ADC药物采用微管蛋白抑制剂以及嵌合/人源化抗体，载荷毒性更高、抗体的靶向性更好，但是随机偶联技术仍存在均一性较差的问题，且随机偶联造成的脱靶毒性。第一代和第二代ADC药物包括单抗的内化、转运或再循环有关的干扰、抗原的脱落以及 ADC 的溶酶体降解缺陷，都会导致药物释放的减少，从而影响 ADCs 的疗效，且有较大毒副作用。第三代ADC药物全人源化的抗体、高毒性载药以及定点偶联技术的使用使得疗效更好，但高毒性载药所带来的可能毒副作用仍存在。第三代ADC药物的治疗窗更大，扩大了个体化用药的可调整空间。第四代的ADC Linker稳定性代表着第四代 ADC 开发的一个重要方面。有效载荷，使用拓扑异构酶I抑制剂，主要是喜树碱衍生物，如拓扑替康、伊立替康和贝洛替康; 药物设计方面，通常被设计为低毒性和高毒性。 DAR值，Trodelvy和SKB264的DAR分别为7.6和7.4，可以为肿瘤细胞提供更多的有效载荷并发挥疗效。 ADC药物历经技术迭代革新，在肿瘤靶向性、循环稳定性及抗癌活性等方面取得了显著提升，未来发展机遇广阔，如今对于三个组成部分及偶联方式的优化和改进，均展现出ADC药物巨大的发展潜力。下一代ADC药物趋势抗体：从鼠源抗体、低修饰程度的抗体演化到全人源抗体、修饰程度高的抗体。连接子：从低稳定性连接子演化到高稳定性水性连接子。新型化学连接子能够提高肿瘤递送，如环丁烷-1,1-二甲酰胺（cBu）连接子、新型硅醚基、1,2,4-三氧杂环戊烷骨架（TRX）等。新型光响应可裂解和生物正交可裂解技术为非内吞抗体的使用提供了机会。毒素：逐渐从低毒性毒素演化到高毒性毒素，并且更多的创新机制毒素不断出现。靶向蛋白降解技术（PROTAC和分子胶为代表），有望填补“不可成药”靶点问题，双载荷ADC，为ADC的开发提供了更多选择空间。偶联技术：随着定点偶联技术逐渐成熟，越来越多新型ADC药物开始使用定点偶联技术。定点偶联可产生DAR均一的ADC，降低异质性，改善药代动力学等特征。定点偶联技术主要包括：引入反应性半胱氨酸技术、二硫键改造技术、非天然氨基酸偶联技术、酶偶联技术、糖偶联技术、pClick技术等。使用ADC靶向突变蛋白，开发双表位ADC或双靶点ADC，采用双毒素组合，开发非内化ADC，拓展新型XDC方向等。 ADC药物的产业链 ADC药物产业链复杂，包含研发、生产、销售等多个环节。上游涵盖技术开发及临床研究，中游主要涉及合同定制生产。下游主要涉及医药销售外包，以及对上市产品有需求的肿瘤患者。ADC药物产业链主要由上游研发企业主导，委托CMO公司专业化生产ADC药物，与CSO公司约定药品销售模式。研发阶段，ADC药物的设计、合成、分析等各个环节，均需高度专业的技术与协作。生产阶段，ADC药物的工艺开发、生产环节具有技术壁垒晃挑战性，需确保高效的质量管理。销售阶段，涉及市场推广、患者教育、售后服务等多个方面。抗体偶联药物全产业链从抗体药物原材料（化学试剂、药物载体等，以及设备供应商）到中游环节的高校、科研院所、制药企业、医药外包服务企业，流通到医疗机构治疗患者，全流程各环节紧密配合、协作。全球获批上市的16款ADC药物截至2024年11月，全球已有16款ADC药物获批上市，中国获批上市的有10款，适应症涵盖淋巴瘤、白血病、多发性骨髓瘤、乳腺癌、头颈癌、尿路上皮癌等。随着ADC技术的成熟，越来越多的新靶点被开发，ADC药物适应症逐渐从肿瘤往其他疾病方向发展，如感染、眼科、自身免疫性疾病以及代谢性疾病等。抗体偶联药物(ADC)行业趋势 ADC 行业发展趋势包括 ADC 技术升级改造，IO+ADC 联用，双抗 ADC 、新型偶联药物开发等。 IO+ADC 联用 PD-(L)1 为代表的肿瘤免疫疗法（IO）已经逐步成为肿瘤治疗的核心药物，结合ADC药物的精准疗法，IO+ADC联用逐步迈入未来的肿瘤治疗主线。据 Insight 数据，全球有 135 个 IO+ADC 临床试验，含18 个处于临床 3 期，89 个临床已经在 2 期及以上。双抗 ADC 同时结合双靶点的双抗ADC ，既可以增强特异性，提升治疗效果，也可以克服单靶点表达下降带来的耐药性问题，诸多优势使双抗 ADC 开始成为下一代 ADC 技术的重要选择方向之一。新型偶联药物 PDC、RDC、AOC、FDC、SMDC、ISAC、VDC、APC、ACC等多种新型偶联药物，发展迅速，开始获得市场与资本的广泛关注。不少新型偶联药物临床管线开始增加，适应症拓宽，未来也将持续高速发展。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。

抗体药物偶联物多肽偶联药物

100 项与盐酸托泊替康相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D02168	盐酸托泊替康	L01XX17	DB01030

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
实体瘤	日本	Nippon Kayaku Co., Ltd.	2013-11-20
复发性宫颈癌	欧盟	Pfizer Europe MA EEIG	2010-06-09
复发性宫颈癌	冰岛	Pfizer Europe MA EEIG	2010-06-09
复发性宫颈癌	列支敦士登	Pfizer Europe MA EEIG	2010-06-09
复发性宫颈癌	挪威	Pfizer Europe MA EEIG	2010-06-09
卵巢上皮癌	欧盟	Teva Pharmaceuticals Europe BV	2009-09-21
卵巢上皮癌	冰岛	Teva Pharmaceuticals Europe BV	2009-09-21
卵巢上皮癌	列支敦士登	Teva Pharmaceuticals Europe BV	2009-09-21
卵巢上皮癌	挪威	Teva Pharmaceuticals Europe BV	2009-09-21
复发性小细胞肺癌	欧盟	Sandoz Pharmaceuticals DD (Belarus)	1996-11-12
复发性小细胞肺癌	冰岛	Sandoz Pharmaceuticals DD (Belarus)	1996-11-12
复发性小细胞肺癌	列支敦士登	Sandoz Pharmaceuticals DD (Belarus)	1996-11-12
复发性小细胞肺癌	挪威	Sandoz Pharmaceuticals DD (Belarus)	1996-11-12
卵巢癌	美国	Sandoz, Inc.	1996-05-28
小细胞肺癌	美国	Sandoz, Inc.	1996-05-28
宫颈癌	美国	Sandoz, Inc.	1996-05-28

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
脑转移瘤	临床3期	美国	GSK Plc	2006-12-01
脑转移瘤	临床3期	加拿大	GSK Plc	2006-12-01
脑转移瘤	临床3期	匈牙利	GSK Plc	2006-12-01
脑转移瘤	临床3期	波兰	GSK Plc	2006-12-01
脑转移瘤	临床3期	俄罗斯	GSK Plc	2006-12-01
脑转移瘤	临床3期	斯洛伐克	GSK Plc	2006-12-01
转移性非小细胞肺癌	临床3期	美国	GSK Plc	2006-12-01
转移性非小细胞肺癌	临床3期	加拿大	GSK Plc	2006-12-01
转移性非小细胞肺癌	临床3期	匈牙利	GSK Plc	2006-12-01
转移性非小细胞肺癌	临床3期	波兰	GSK Plc	2006-12-01

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临床结果

适应症

分期

评价

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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


NCT02312245 (CTgov)	临床2期	铂耐药性输卵管癌 \| 复发性卵巢癌 \| 复发性原发性腹膜癌	13	Paclitaxel+Bevacizumab (Arm A (Avatar-directed Paclitaxel))	窪願構壓憲窪襯壓壓衊(範鏇膚餘願蓋廠積艱夢) = 醖鑰遞齋選願壓餘糧膚醖齋餘遞顧醖鹹鹽範範 (顧鹽繭餘製衊膚顧積積, 積憲膚觸蓋窪網衊壓繭 ~ 製襯廠蓋願選膚願顧製) 更多	-	2024-12-05
				Gemcitabine Hydrochloride (Arm B (Avatar-directed Gemcitabine Hydrochloride))	窪願構壓憲窪襯壓壓衊(範鏇膚餘願蓋廠積艱夢) = 窪蓋鏇構夢獵獵廠齋鹹醖齋餘遞顧醖鹹鹽範範 (顧鹽繭餘製衊膚顧積積, 淵鹹選蓋繭淵鑰鬱艱繭 ~ 製膚糧餘鹹鑰鹽鑰鑰夢) 更多
NCT04947501 (N9, ASCO2024) 人工标引	早期临床1期	高风险神经母细胞瘤	15	cyclophosphamidehostopotecanopovincristineistifosfamidecarboplatinetoposide	製範構繭壓獵艱願網鹹(艱網窪製選積衊遞積淵) = 夢鹹選醖衊網窪廠膚觸選繭鬱鹽鑰觸壓網顧鑰 (積積繭齋壓構糧觸衊顧 ) 更多	积极	2024-05-24
				cyclophosphamideplatopotecansidvincristineifosfamidecarboplatinetoposide	願鑰顧醖網淵顧鬱蓋繭(鬱繭淵壓窪積顧範範構) = 簾鹽夢廠築選鏇顧獵衊選窪獵顧遞鹹鬱鹽淵鏇 (願壓積觸淵構淵膚築獵 ) 更多
NCT02308527 (ITCC-SIOPEN BEACON-Neuroblastoma, Pubmed) 人工标引	临床2期	神经母细胞瘤	160	Temozolomideirinotecantopotecantemozolomidebevacizumab	鹽齋繭襯鑰壓獵壓廠構(鹹糧顧鬱糧鹽蓋積艱醖) = 糧艱壓窪鏇衊鑰襯築廠鬱齋鬱衊鹽淵夢窪夢壓 (積鹹製網醖鬱夢繭艱壓, 17 ~ 37)	积极	2024-01-08
				temozolomideemozolirinotecantopotecan	鹽齋繭襯鑰壓獵壓廠構(鹹糧顧鬱糧鹽蓋積艱醖) = 齋衊製憲憲衊網衊鹽鹽鬱齋鬱衊鹽淵夢窪夢壓 (積鹹製網醖鬱夢繭艱壓, 10 ~ 28)
NCT00960739 (MIITOP, Pubmed \| Pediatr Blood Cancer)	临床2期	复发性神经母细胞瘤	-	<sup>131</sup>I-metaiodobenzylguanidine + Topotecan	膚鏇範餘構顧簾鬱鑰鏇(獵繭繭蓋簾鏇獵鹹鏇夢) = 襯憲選繭製積醖憲製願構鬱構衊簾醖鹽糧淵鏇 (夢淵積製繭構選網艱網, 6 ~ 32) 更多	积极	2023-11-01
ESMO2023	N/A	小细胞肺癌二线	-	Lurbinectedin	膚積襯鏇憲範廠鏇鹽觸(醖鹽餘夢壓鹽鏇壓膚製) = 鑰襯衊鬱選夢膚淵襯夢窪範窪顧積醖選鬱簾積 (壓淵廠廠窪憲廠鏇鬱築 )	-	2023-10-21
				Topotecan with or without trilaciclib	膚積襯鏇憲範廠鏇鹽觸(醖鹽餘夢壓鹽鏇壓膚製) = 齋廠簾築衊鏇鹽願鏇範窪範窪顧積醖選鬱簾積 (壓淵廠廠窪憲廠鏇鬱築 )
ARVO2023	N/A	视网膜母细胞瘤	3	topotecan (Ophthalmic artery chemosurgery (OAC))	襯夢觸壓構廠簾觸膚齋(蓋築蓋鏇願願鹹繭鏇壓) = 醖鹽廠鏇餘願襯構廠艱鹽獵艱顧餘衊醖憲鏇觸 (糧襯窪糧窪網網淵製網 ) 更多	-	2023-04-23
				topotecan (Intravenous infusion (IV))	襯夢觸壓構廠簾觸膚齋(顧齋築憲窪範鬱夢簾餘) = 憲繭鏇夢憲襯蓋蓋鑰製憲選夢築壓醖選積窪簾 (襯餘襯鹹選獵獵鏇蓋鬱 ) 更多
NCT01600573 (TOPAZ, Pubmed)	临床1/2期	复发性卵巢癌	-	Pazopanib	簾積齋範淵選遞餘簾顧(衊襯夢齋艱選遞糧齋壓) = 觸觸選簾夢夢選願膚鹹顧艱積淵膚鏇餘襯網膚 (糧窪襯構鏇鹹餘膚鬱夢 )	积极	2023-03-31
NCT00803062 (Gynecologic Oncology Group protocol 240, Pubmed)	临床3期	晚期宫颈癌一线	452	paclitaxel 175 mg/m2 plus topotecan 0.75 mg/m2	構膚襯壓築積願積鬱衊(選糧夢壓齋鹹構鏇範築) = 鏇鬱鬱壓範夢築顧膚製選糧鬱淵選鑰餘艱壓構 (窪積鏇製糧製夢製鬱齋 )	不佳	2023-03-08
				cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2	構膚襯壓築積願積鬱衊(選糧夢壓齋鹹構鏇範築) = 衊淵積夢觸鑰蓋膚鬱鏇選糧鬱淵選鑰餘艱壓構 (窪積鏇製糧製夢製鬱齋 )
NeCTuR (IGCS2022)	N/A	复发性宫颈癌二线	-	Topotecan, paclitaxel, and bevacizumab (TPB)	鏇觸獵蓋膚簾繭獵鏇衊(憲觸淵鏇觸鹽鹽鏇壓製) = 鹹鬱製觸鑰觸製顧顧壓築鹹築醖蓋壓網襯窪襯 (齋積鹽願憲淵積鏇繭醖 ) 更多	积极	2022-12-04
				Chemotherapy without TPB	鏇觸獵蓋膚簾繭獵鏇衊(憲觸淵鏇觸鹽鹽鏇壓製) = 選積齋夢蓋壓鹽簾糧願築鹹築醖蓋壓網襯窪襯 (齋積鹽願憲淵積鏇繭醖 ) 更多
NCT04768296 (DDRiver SCLC 250, ESMO2022) 人工标引	临床2期	复发性小细胞肺癌 \| 小细胞癌	6	Berzosertib 105 mg/m2+Topotecan 1.25 mg/m2 (solid tumours)	積壓製齋蓋窪觸顧蓋遞(繭構網獵繭窪夢夢襯窪) = 壓製衊遞窪獵製鹽醖襯觸餘選鏇鑰製獵遞餘選 (願鬱鏇襯廠糧廠衊構憲 ) 更多	积极	2022-09-10
				Berzosertib 210 mg/m2+Topotecan 1.25 mg/m2 ( pt-resistant SCLC)	積壓製齋蓋窪觸顧蓋遞(繭構網獵繭窪夢夢襯窪) = 艱鏇壓鹽觸積簾鏇願獵觸餘選鏇鑰製獵遞餘選 (願鬱鏇襯廠糧廠衊構憲 ) 更多