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-

NCT06930755

/ Not yet recruiting临床1期

Study of NMS-03305293, a Non-Trapping PARP1-Specific PARP Inhibitor in Relapsed Ovarian Cancer

This is a multicenter, open-label Phase Ia/b study on the safety and efficacy of the combination of NMS-03305293 and topotecan in patients with recurrent ovarian cancer, with dose-limiting toxicity (DLT) escalation. The aim of this study is to determine the safety and tolerability, as well as to evaluate the anti-tumor efficacy and pharmacokinetics of NMS-03305293 in combination with topotecan.

开始日期2025-06-28

申办/合作机构

Nerviano Medical Sciences S.r.l

NCT06942039

/ Not yet recruiting早期临床1期

A Pilot Study of Intrathecal Topotecan and Maintenance Chemotherapy in the Post-consolidation Setting for the Treatment of High-risk Embryonal Central Nervous System Tumours in Children Less Than 6 Years of Age

Pilot study to determine feasibility of adding intrathecal chemotherapy and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age.

开始日期2025-06-01

申办/合作机构

C17 Council

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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5,458

项与盐酸托泊替康相关的文献（医药）

2025-08-01·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Simultaneous analysis of various anticancer drugs by supercritical fluid chromatography-mass spectrometry. Part I: Optimization of chromatographic separation

Article

作者: Guillarme, Davy ; Rudaz, Serge ; Fleury-Souverain, Sandrine ; Bonnabry, Pascal ; Nguyen, Nathalie

This work presents a generic SFC-MS method for the simultaneous analysis of 22 anticancer drugs (fluorouracil, busulfan, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, gemcitabine, idarubicin, ifosfamide, irinotecan, methotrexate, paclitaxel, pemetrexed, raltitrexed, topotecan, treosulfan, vinblastine, vincristine). The separation conditions were optimized by screening nine stationary phases (2-picolylamine, bare hybrid silica, 2-ethylpyridine, fluoro-phenyl, octadecyl, diethylamine, diol, 1-aminoanthracene, zwitterionic modification), evaluating additives effects (2-5 % water, 20-50 mM ammonium formate, 0-1 mM ammonium fluoride), and adjusting the organic modifier composition (methanol, ethanol, isopropanol, acetonitrile). The optimized SFC-MS method successfully analyzed 22 anticancer drugs, along with 5 additional challenging compounds (azacitidine, mitomycin, cisplatin, oxaliplatin, carboplatin), in 12 min, using a diol column (100 × 3 mm, 1.7 µm) and a gradient of 2-100 % methanol containing 2 % water and 50 mM ammonium formate. To overcome overpressure generated by high organic solvent content, a backpressure gradient (110-150 bar) and a flow rate gradient (0.6-1.5 mL/min) were applied. The diol column was selected as the most promising based on five predefined chromatographic criteria. Additives with 5 % water or ammonium fluoride were excluded due to overpressure and signal loss, respectively. Increasing ammonium formate concentration improved peak symmetry by 29 %. For the organic modifier, pure methanol was chosen since ternary mixtures led to system overpressure without improving separation. Comparison with the LC-MS method using real samples confirmed the potential applicability of the SFC method, as the same trace compounds were detected with comparable concentrations. Sensitivity optimization and method validation will be discussed separately in a later paper.

2025-07-01·PEDIATRIC BLOOD & CANCER

Identification of Anticancer Drugs Associated With Cancer Therapy‐Related Cardiac Dysfunction in Pediatrics—Analysis of the WHO Pharmacovigilance Database

Article

作者: Rouger, Jérémie ; Dolladille, Charles ; Labombarda, Fabien ; Chrétien, Basile ; Alexandre, Joachim ; Legallois, Damien

ABSTRACT:

Aims:

Cardiovascular toxicities associated with anticancer drugs constitute a significant concern for pediatric patients undergoing cancer treatment. Comprehensive data on the burden of cancer therapy‐related cardiac dysfunction (CTRCD) are lacking, particularly for this high‐risk population susceptible to develop myocardial toxicity. By analyzing VigiBase, the World Health Organization's individual case safety report database, we sought to determine anticancer drugs associated with CTRCD in pediatric patients.

Methods and Results:

To evaluate the association between 249 anticancer drugs labeled by the FDA or EMA and CTRCD reporting, we performed a disproportionality analysis, calculating multivariable adjusted reporting odds ratios (aROR) with their 95% confidence intervals (CI) across four pediatric age classes (0–27 days, 28 days to 23 months, 2–11 years, 12–17 years); ClinicalTrial registration number: NCT05602103. We identified 796 cases of CTRCD associated with at least one anticancer drug in VigiBase. Multivariate analysis across the pediatric age spectrum revealed 16 anticancer drugs significantly associated with CTRCD, of which 10 (63%) are primarily used for hematologic malignancies. Two drugs, a topoisomerase 1 inhibitor (topotecan) and cytotoxic antibiotics (dactinomycin), represented novel associations with CTRCD not previously documented in the literature.

Conclusion:

Within VigiBase, we pinpointed 16 anticancer drugs significantly associated with CTRCD reporting in pediatrics. Our research validated several associations already thoroughly reported in children (such as with anthracyclines), and unveiled novel signals for systemic exposure to topotecan and dactinomycin. The relevance of these findings, especially considering the frequency of co‐administration of agents and the lack of information regarding radiation exposure and chemotherapy dosage, would need to be evaluated in the context of clinical trials that use or have used these agents.

2025-06-01·INDIAN JOURNAL OF OPHTHALMOLOGY

Do’s and Don’ts” for intraarterial chemotherapy for retinoblastoma- What ophthalmologist and interventional radiologist need to know?

Review

作者: Gupta, Vipul ; Das, Sima ; Bhatter, Pallav ; Parthasarathy, Rajsrinivas ; Aggarwal, Ujjwal ; Kumar, Pallav ; Dusa, Srinivas Rao

Intra-arterial chemotherapy (IAC) has emerged as the primary treatment option for retinoblastoma management. It enables the localized delivery of a higher concentration of chemotherapeutic agents (melphalan, carboplatin and topotecan) in the ophthalmic artery, enhancing tumour control and potentially avoiding the need for enucleation. Nevertheless, procedure-related complications have raised concerns. In this article, we outline the various technical considerations for performing safe IAC and minimizing procedure-related complications.

315

项与盐酸托泊替康相关的新闻（医药）

2025-06-05

·医学新视点

死亡风险显著降低40%！双特异性抗体为肺癌治疗提供新选择 | 2025 ASCO速递

小细胞肺癌复发后治疗选择有限。Tarlatamab是双特异性T细胞衔接器（BiTE），代表一类具有显著抗肿瘤效应的双特异性抗体，能够靶向性激活自身T细胞杀伤肿瘤细胞。既往研究显示，对于既往接受过治疗的小细胞肺癌（SCLC）患者，tarlatamab展示出具有希望的抗肿瘤活性。但尚不明确在初始铂类化疗期间或化疗后疾病进展的SCLC患者中，tarlatamab的抗肿瘤效果如何？2025年美国临床肿瘤学会年会（2025 ASCO）上，Ph3 DeLLphi-304的初步分析结果发表，表明在铂类化疗期间或化疗后疾病进展的SCLC患者中，相比于单纯化疗，tarlatamab作为二线治疗方案，可显著提高中位总生存期（OS，13.6个月 vs. 8.3个月），死亡风险降低40%，并同时改善中位无进展生存期（PFS，4.2个月 vs. 3.2个月），安全性可控。这一结果为复发性SCLC提供了新的治疗选择。该研究入选了本届ASCO的最新科学进展（Late Breaking Abstracts，LBA），结果同步发表于《新英格兰医学杂志》（NEJM）。截图来源：ASCOPh3 DeLLphi-304试验在全球多个国家开展，研究人员将铂类化疗期间或化疗后疾病进展的509例SCLC患者随机分为两组，其中254例接受tarlatamab治疗，255例接受化疗（托泊替康、芦比替定或amrubicin）。主要终点为OS，关键次要终点包括PFS和患者报告的结局改善情况。截至2025年1月29日，tarlatamab组和化疗组中位随访时间分别为11.2个月和11.7个月。tarlatamab组生存获益更显著，中位OS达13.6个月，而化疗组仅8.3个月，tarlatamab组死亡风险显著降低40%（HR=0.60，95%CI：0.47~0.77，P＜0.001）；tarlatamab组的中位PFS也显著长于化疗组（4.2个月 vs. 3.2个月），tarlatamab组疾病进展或死亡风险显著降低28%（HR=0.72，95%CI：0.59~0.88，P＜0.001）。tarlatamab组患者报告的癌症相关呼吸困难、咳嗽等症状改善优于化疗组，具体而言：欧洲癌症治疗研究组织（EORTC）生命质量测定量表（QLQ-C30，分为功能评分和症状评分，其中症状评分分值越高，表示患者症状越严重）评分显示，tarlatamab组和化疗组治疗第18周时，呼吸困难评分较基线分别降低1.94分和增加7.20分（P＜0.001）；基于EORTC肺癌患者生命质量量表（QLQ-LC13，症状评分分值越高，表示患者症状越严重）评分，治疗18周时，tarlatamab组咳嗽和胸痛症状显著改善的患者比例分别为16%（41例）和9%（22例），高于化疗组的9%（23例）和4%（9例）。安全性方面，相比于化疗组，tarlatamab组3级及以上治疗相关不良事件发生率更低（27% vs. 62%），因治疗相关不良事件停药率也更低（3% vs. 6%）。化疗组常见3级及以上治疗相关不良事件为中性粒细胞减少症、淋巴细胞减少症，而tarlatamab组主要为低级细胞因子释放综合征，且整体可控。本研究表明，tarlatamab在复发性SCLC的二线治疗中带来了更好生存获益，且安全性可控。有望为这部分患者的治疗提供新选择。点击文末“阅读原文/Read more”，即可访问ASCO官网阅读摘要。推荐阅读欢迎投稿：学术成果、前沿进展、临床干货等主题均可，点此了解投稿详情。参考资料[1]Giannis Mountzios, Longhua Sun, Byoung Chul Cho, et al. Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy. New England Journal of Medicine. Advance online publication. https://doi-org.libproxy1.nus.edu.sg/10.1056/NEJMoa2502099免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医学新视点」微信公众号留言联系。如有其他合作需求，请联系wuxi_media@wuxiapptec.com分享，点赞，在看，传递医学新知

临床结果ASCO会议

2025-06-04

·奇点网

程颖教授解读ES-SCLC维持治疗，IMforte点亮生命新曙光

*仅供医学专业人士阅读参考在近日的2025年美国临床肿瘤学会（ASCO）年会上，全球性III期关键临床研究IMforte结果重磅发布，并同步以论文形式登上《柳叶刀》，带来了ES-SCLC一线维持治疗的全新选择：对阿替利珠单抗联合化疗一线治疗后未发生疾病进展的患者，阿替利珠单抗+芦比替定双药维持治疗，对比阿替利珠单抗单药维持治疗，取得了双主要终点-独立评审无进展生存期（PFS）和总生存期（OS）双阳性结果。这是在ES-SCLC领域首个维持治疗取得阳性结果的全球III期研究，是ES-SCLC治疗历程上又一项里程碑式的研究！程颖教授吉林省肿瘤医院一级教授，博士研究生导师，博士后工作站导师享受国务院特殊津贴，卫生部突出贡献中青年专家吉林省肿瘤医院恶性肿瘤临床研究一体化诊疗中心主任吉林省癌症中心主任吉林省肺癌诊疗中心主任中国临床肿瘤学会（CSCO) 监事会副监事长北京希思科临床肿瘤学研究基金会副理事长国际肺癌研究协会（IASLC）罕见肿瘤（小细胞肺癌）专委会委员中国抗癌协会小细胞肺癌专委会主任委员CSCO临床研究专家委员会主任委员CSCO小细胞肺癌专家委员会前任主任委员CSCO非小细胞肺癌专家委员会副主任委员中华医学会肿瘤学分会肺癌专委会副主任委员中国医师协会肿瘤多学科诊疗专委会副主任委员2023、2024年度临床医学领域“全球高被引科学家”建立维持治疗新标准，引领ES-SCLC治疗持续向前IMforte研究是一项全球、多中心、随机对照III期关键临床试验，共纳入660例ES-SCLC患者，一线给予阿替利珠单抗+化疗诱导治疗4个周期，此后对疾病无进展的483例患者按1:1比例，随机至阿替利珠单抗+芦比替定维持治疗组或阿替利珠单抗单药维持治疗组，治疗至疾病进展或发生不可耐受的毒性，本研究不允许组间交叉（Crossover）。值得注意的是，IMforte研究采用开放标签设计，且未纳入存在中枢神经系统（CNS）转移的ES-SCLC患者，这两点都与芦比替定有关，一方面是因为它的不良反应，如胃肠道和血液学不良事件及处理策略（如使用止吐药、G-CSF等）较易被医生和患者识别，另一方面则是在IMforte研究启动时，芦比替定对存在CNS转移灶患者的临床获益尚不明确。IMforte研究主要疗效终点为独立评审机构（IRF）评估的患者PFS和OS，次要终点则为研究者评估的PFS，客观缓解率（ORR）、缓解持续时间（DoR）等，各项疗效数据均从维持治疗启动时开始评估。IMforte研究设计在本届ASCO年会上，IMforte研究的主要结果以口头报告形式正式公布：阿替利珠单抗+芦比替定维持治疗组患者的mPFS为5.4个月，显著优于对照组的2.1个月，联合方案维持治疗使患者疾病进展或死亡风险显著下降了46%（HR=0.54, P<0.0001），且各预设亚组获益整体一致；两组mOS则分别为13.2个月和10.6个月，联合方案维持治疗使患者死亡风险相对下降27%（HR=0.73, P=0.0174），关键预设亚组中观察到一致的生存获益。IMforte研究PFS、OS数据安全性数据显示，在阿替利珠单抗+芦比替定维持治疗组患者中位治疗时长达到4.1个月，近乎对照组两倍（2.1个月）的前提下，联合方案维持治疗组发生的大多数不良事件，尤其是血液学不良事件仍程度较轻，多数仅为1-2级，提示研究要求的G-CSF预处理策略，可有效应对芦比替定治疗相关血液学毒性；虽然联合方案组的3-4级治疗相关不良事件（TRAEs）发生率稍高，但整体永久停药率仍较低，反映不良事件大多可管可控。IMforte研究安全性数据IMforte研究PFS和OS双主要终点阳性，实现有统计学意义和临床意义的显著改善，再加上治疗安全性良好，交出的无疑是一份高分答卷，阿替利珠单抗+芦比替定方案也即将由此确立一线维持治疗新标准的地位。专家点评如何提高ES-SCLC患者的生存一直是临床不断攻坚探索的难题，尽管ES-SCLC初始治疗有效率较高，但大部分患者在诱导治疗结束后快速复发，疾病复发后进展迅速，预后极差。如何改善ES-SCLC的生存，有效的维持治疗被认为是巩固一线治疗成果，延长无进展生存时间，进而提高总生存期的重要策略。多年来，ES-SCLC的维持治疗策略不断在进行探索，在经历了非常艰难和曲折的历程后，今年终于迎来了曙光。一、ES-SCLC维持治疗的前世：在困境中的探索在含铂双药化疗作为ES-SCLC标准一线治疗方案时代，针对如何寻找适合的维持治疗策略进行了多样的探索，这时的策略是在诱导化疗结束后，对于疾病未进展的患者探寻有效的维持治疗药物，但是多年来研究进展一直举步维艰。在探索维持治疗的早期阶段，因为SCLC缺乏更多的抗肿瘤药物，对标准EC或EP方案化疗后，维持治疗的探索主要是给予不同化疗药物，几项研究应用口服依托泊苷胶囊维持治疗或者给予拓扑替康等化疗药物维持治疗，但均没有获得生存获益。此后，针对抗血管生成药物在维持治疗阶段的疗效进行了评估，但是无论是大分子的贝伐珠单抗，还是小分子抗血管抑制剂帕唑帕尼等几项II期研究均未达到主要终点。随后，靶向药物、ADC和免疫药物也进行了维持治疗的探索。在PARP抑制剂方面，应用尼拉帕利维持治疗的III期研究结果显示仅有轻微的PFS获益，但OS没有获益；在早期靶向DLL3的ADC药物方面，MERU这项III期研究应用Rova-T进行维持治疗，由于该药物的毒性维持治疗也没有显示出OS获益，并停止在SCLC的研发；进入免疫治疗时代，CheckMate-451研究作为免疫治疗领域第一个，在标准化疗4周期结束后，免疫维持治疗的III期研究，结果显示纳武利尤单抗单药或者纳武利尤单抗联合伊匹木单抗作为维持治疗，两组都没有带来OS获益。因此，无论是化疗、抗血管生成治疗、PARP抑制剂、ADC药物还是免疫治疗，一线采用标准化疗结束后给予维持治疗均纷纷折戟，维持治疗在ES-SCLC一度停滞不前。二、ES-SCLC维持治疗的今生：拨开迷雾见曙光近年来，免疫联合化疗一线治疗ES-SCLC实现了里程碑式的跨越，目前免疫联合化疗诱导治疗4~6个周期后，给予免疫单药维持治疗成为标准治疗策略。在IMpower133研究的探索性分析中发现，自维持治疗开始阿替利珠单抗组的中位OS和PFS分别为12.5个月和2.6个月，均高于安慰剂对照组的8.4个月和1.8个月，死亡风险和疾病进展风险得到进一步下降（HR为0.59和0.63），意味着在一线ES-SCLC免疫联合化疗带来的生存获益基础上，继续免疫维持治疗同样有着重要贡献。因此，ES-SCLC一线化疗联合免疫治疗后，维持治疗是提高患者生存的重要探索方向。如何能够进一步提高维持治疗的疗效，以及针对SCLC冷肿瘤的微环境特点，多种以免疫为基础的联合治疗策略进行了探索。在免疫联合化疗维持治疗方面，此次ASCO年会上报告的IMforte研究采用阿替利珠单抗联合芦比替定维持治疗。芦比替定已获批ES-SCLC二线治疗适应证，从作用机制上看，芦比替定不仅有抑制癌基因转录、诱导癌细胞凋亡的主要功能，还在临床前研究中展现了通过减少巨噬细胞数量、抑制肿瘤新生血管形成、诱导癌细胞免疫原性死亡等方式，正向调节肿瘤微环境的作用。在临床研究方面，I期数据表明阿替利珠单抗联合芦比替定作为ES-SCLC二线治疗的ORR为58%，患者中位PFS达到4.93个月，提示该联合方案具有较好的抗肿瘤活性。IMforte研究也是首个在ES-SCLC维持治疗阶段，成功取得PFS和OS双阳性结果的III期研究，实现了在IMpower133研究基础上进一步延长患者生存的目标，在ES-SCLC维持治疗领域具有开创性的意义。在免疫联合抗血管维持治疗方面，DURABLE研究是一项度伐利尤单抗联合安罗替尼对比度伐利尤单抗维持治疗的II期研究，研究显示从诱导治疗开始，度伐利尤单抗联合安罗替尼维持治疗和度伐利尤单抗单药维持治疗组的PFS分别为9.0个月和5.6个月，OS分别为20.4个月和15.4个月，这项研究提示免疫联合多靶点抗血管药物维持治疗是具有前景的研究方向。此外，我们牵头进行的ETER701研究，在诱导化疗开始时给予安罗替尼联合贝莫苏拜单抗四药联合治疗，然后给予安罗替尼联合贝莫苏拜单抗维持治疗，PFS和OS分别6.9个月和19.3个月，PFS和OS数据均得到显著延长，OS延长7.4个月显著优于既往免疫联合化疗一线治疗的历史数据，结果进一步支持免疫联合抗血管维持治疗具有很好的疗效和安全性。在免疫联合DLL3/CD3双抗维持治疗方面，DeLLphi-303 研究是一项塔拉妥单抗联合PD-L1抑制剂维持治疗ES-SCLC的1b期研究，塔拉妥单抗联合PD-L1抑制剂维持治疗的 PFS 为 5.6 个月，安全性良好，为正在进行的塔拉妥单抗联合度伐利尤单抗维持治疗的III期研究DeLLphi-305研究提供了支持，该研究也可能成为SCLC免疫维持治疗的下一个突破口。在免疫联合PARP抑制剂维持治疗方面，SWOG S1929研究是一项评估阿替利珠单抗联合他拉唑帕利对比阿替利珠单抗维持治疗的II期研究，纳入一线阿替利珠单抗联合化疗治疗未进展且SLFN11阳性ES-SCLC患者，结果显示SLFN11阳性患者联合维持治疗PFS有一定获益趋势；一项I期研究评估奥拉帕利联合度伐利尤单抗维持治疗的疗效和安全性正在进行中，未来仍有待进一步的结果公布。此外，在免疫联合放疗维持治疗方面，一项II期研究在ES-SCLC患者接受阿得贝利单抗联合化疗4~6个周期诱导治疗后，对产生应答的患者给予阿得贝利单抗联合胸部巩固放疗，后续再给予阿得贝利单抗维持治疗。结果显示，中位PFS为10.1个月，中位OS为21.4个月，接受和未接受胸部放疗患者的中位OS分别为22.9个月和13.4个月，与仅接受免疫单药维持治疗的历史数据相比，免疫联合放疗巩固维持治疗的模式患者生存数据有一定提高，但仍需III期研究的进一步验证。三、ES-SCLC维持治疗的未来：探索分子分型和生物标记物指导的治疗在ES-SCLC维持治疗策略中，以生物标记物或分子分型指导的维持治疗策略将是重要的探索方向。目前，尚没有生物标志物来指导SCLC维持治疗的治疗决策。近年来，一些研究对SCLC免疫治疗的生物标志物进行了探索，研究结果显示RB1突变状态、MYC表达、肿瘤浸润淋巴细胞、表观遗传异常和肿瘤新抗原等生物标记物可能是SCLC免疫治疗潜在生物标志物。在一项临床前的研究中，研究者发现SLFN11高表达的细胞系对芦比替定更敏感，SLFN11低表达鼠模型对芦比替定的敏感性明显较低，SLFN11可能预测对芦比替定的敏感性。这些生物标记物在SCLC的应用还有很长的路要走，仍需要更多前瞻性研究进一步的验证。基于分子分型的研究可能为SCLC免疫治疗带来了新的方向。根据关键转录因子的表达，SCLC可分为不同的转录亚型，如SCLC - A、SCLC - N、SCLC - P和SCLC - Y/I等。不同亚型具有不同的生物学特性和治疗敏感性，SCLC - Y/I亚型免疫细胞浸润和检查点分子表达较高，患者的OS有延长趋势；SCLC-P亚型则与较差的预后相关。在免疫联合治疗策略中，SCLC-Y/I亚型显示出预测疗效的潜力；SCLC-A和SCLC-N亚型中DLL3表达较高，可能与对Tarlatamab的治疗应答有关。但转录亚型在预测 ICI 单药治疗效果时存在局限性，多组学整合研究有助于更全面地了解SCLC的生物学特性，分子分型作为免疫治疗生物标志物的可靠性还需更多前瞻性临床研究验证。四、总结芦比替定联合阿替利珠单抗维持治疗的成功标志着ES-SCLC治疗迈出重要一步，新兴治疗策略的发展为SCLC维持治疗提供了新的机遇，随着更多创新型药物在SCLC领域的不断探索以及研究结果的公布，将为ES-SCLC一线维持治疗提供更多治疗选择，未来维持治疗的格局可能进一步多元化。如何筛选维持治疗的获益人群，优化维持治疗的联合策略仍然充满着挑战，随着对SCLC生物学的深入了解和生物标记物的研发，未来有望为SCLC患者带来新的希望。参考文献：[1]Rudin C M, Liu S V, Soo R A, et al. SKYSCRAPER-02: tiragolumab in combination with atezolizumab plus chemotherapy in untreated extensive-stage small-cell lung cancer[J]. Journal of Clinical Oncology, 2024, 42(3): 324-335.[2]Ohe Y, Han B, Nishio M, et al. BEAT-SC: A randomized phase III study of bevacizumab or placebo in combination with atezolizumab and platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC)[J]. Journal of Clinical Oncology, 2024, 42(16_suppl): 8001.[3]Reck M, Dziadziuszko R, Sugawara S, et al. Five-year survival in patients with extensive-stage small cell lung cancer treated with atezolizumab in the Phase III IMpower133 study and the Phase III IMbrella A extension study[J]. Lung Cancer, 2024, 196: 107924.[4]Kao S C H, Reck M, Liu S V, et al. 634P Whole exome sequencing (WES) analyses from IMpower133 and 6-year (y) overall survival (OS) from IMbrella A in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC) treated with atezolizumab (atezo)[J]. Annals of Oncology, 2024, 35: S1638.[5]Reck M, Mok T S K, Mansfield A, et al. Brief report: exploratory analysis of maintenance therapy in patients with extensive-stage SCLC treated first line with atezolizumab plus carboplatin and etoposide[J]. Journal of Thoracic Oncology, 2022, 17(9): 1122-1129.[6]Zhang S, Cheng Y. Immunotherapy for extensive-stage small-cell lung cancer: current landscape and future perspectives[J]. Frontiers in Oncology, 2023, 13: 1142081.[7]Aix S P, Navarro A, Bernabe R, et al. 464 2SMALL (NCT04253145) phase I part: lurbinectidine (LUR) in combination with atezolizumab (ATZ) for second line extensive stage small cell lung cancer (ES-SCLC) patients (pts)[J]. Journal for Immunotherapy of Cancer, 2021, 9(Suppl 2): A493.

ASCO会议临床3期临床结果CSCO会议

2025-06-02

·Firstwordpharma

ASCO25: Amgen's Imdelltra cuts lung cancer death risk by 40% versus chemo

Amgen's DLL3-targeting T-cell engager Imdelltra (tarlatamab-dlle) has delivered on its promise, reducing the risk of death by 40% compared to standard chemotherapy in relapsed small-cell lung cancer (SCLC), according to Phase III data presented at the American Society of Clinical Oncology (ASCO) annual meeting Monday and published in NEJM.The readout provides confirmatory evidence for a drug that received accelerated FDA approval last year based on tumour response rates.The DeLLphi-304 trial, which was toplined in April, involved 509 patients who progressed on or after one line of platinum-based chemotherapy. The new interim data showed that Imdelltra extended median overall survival to 13.6 months versus 8.3 months for regional standard treatments such as topotecan, lurbinectedin or amrubicin. The secondary endpoint of progression-free survival also improved significantly, with patients achieving a median 4.2 months compared to 3.7 months for controls, representing a 29% relative gain.Imdelltra, which binds DLL3 on tumour cells and CD3 on T-cells, targets a protein expressed in up to 96% of SCLC cases — but is largely absent from healthy tissue. That selectivity appeared to translate to better tolerability: only 27% of patients on Imdelltra experienced Grade ≥3 treatment-related adverse events (vs. 62% on chemo), and just 3% discontinued due to side effects (vs. 6%).Imdelltra already comes with a boxed warning about cytokine release syndrome (CRS) and neurologic toxicities (see – Spotlight On: Amgen safely ushers in long-waited arrival of DLL3s in SCLC).Amgen said CRS was mostly low-grade in the trial and occurred primarily after the first two doses (42% Grade 1; 13% Grade 2; 1% Grade 3), with no Grade 4/5 events. "The predictable and manageable profile of cytokine release syndrome enabled the duration of the post-infusion monitoring period after the first two infusions to be reduced from 48-hour inpatient monitoring to 6-to-8-hour outpatient monitoring," the study authors wrote in the NEJM paper.Immune effector cell–associated neurotoxicity syndrome (ICANS), another class-specific side effect of the drug, "occurred infrequently and was generally of low grade and manageable with glucocorticoid treatment," researchers added.Amgen is conducting additional late-stage trials — DeLLphi-305, DeLLphi-306 and DeLLphi-312 — that are testing Imdelltra in earlier treatment lines, including studies combining the drug with AstraZeneca's Imfinzi (durvalumab) as first-line maintenance therapy in extensive-stage SCLC, and following chemoradiotherapy in limited-stage disease.

ASCO会议临床结果临床3期加速审批上市批准

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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

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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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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))	淵蓋鏇糧艱鑰齋夢製艱 = 夢網廠艱窪淵製鬱襯憲積鑰簾艱獵鑰鹹夢簾鑰 (淵願糧醖淵簾遞選衊遞, 膚簾鹹齋築夢遞鹹膚選 ~ 衊餘簾繭鏇觸醖襯積選) 更多	-	2024-12-05
				Gemcitabine Hydrochloride (Arm B (Avatar-directed Gemcitabine Hydrochloride))	淵蓋鏇糧艱鑰齋夢製艱 = 艱鹹夢簾廠衊壓鑰顧膚積鑰簾艱獵鑰鹹夢簾鑰 (淵願糧醖淵簾遞選衊遞, 網衊選廠夢壓壓衊衊積 ~ 鏇顧簾壓淵鹹淵製淵鏇) 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	簾範壓齋壓網積廠網範(選繭糧築鬱餘觸鹽齋鹽) = 願衊築鏇鹽選醖膚範鹹鑰願積範蓋鏇艱醖鑰簾 (構製艱齋築壓餘簾構艱 ) 更多	积极	2024-05-24
				cyclophosphamideplatopotecansidvincristineifosfamidecarboplatinetoposide	醖膚獵鑰齋膚鏇範鏇鑰(繭齋觸範衊憲糧齋網廠) = 夢糧淵簾鏇膚襯襯顧顧構顧繭憲繭餘積夢餘願 (衊鬱網壓艱遞鏇艱夢艱 ) 更多
NCT02308527 (ITCC-SIOPEN BEACON-Neuroblastoma, Pubmed) 人工标引	临床2期	神经母细胞瘤	160	Temozolomideirinotecantopotecantemozolomidebevacizumab	網夢壓醖獵廠觸糧衊網(鹹遞鹹鬱遞繭淵積簾襯) = 繭壓願築鬱願繭獵齋顧窪衊積構範簾廠築鏇衊 (簾顧廠廠艱膚廠觸夢繭, 17 ~ 37)	积极	2024-01-08
				temozolomideemozolirinotecantopotecan	網夢壓醖獵廠觸糧衊網(鹹遞鹹鬱遞繭淵積簾襯) = 製鹽製製鹹繭積觸鬱憲窪衊積構範簾廠築鏇衊 (簾顧廠廠艱膚廠觸夢繭, 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	鬱範糧膚繭窪顧構獵壓(膚鑰鹹艱廠簾膚範憲遞) = 糧獵艱鏇積顧蓋築憲膚膚醖齋壓夢鏇壓觸顧積 (壓壓選襯構顧選選壓壓, 6 ~ 32) 更多	积极	2023-11-01
ESMO2023	N/A	小细胞肺癌二线	-	Lurbinectedin	糧觸夢壓艱醖淵壓遞鬱(鏇醖簾夢鹽襯繭獵獵網) = 鑰築夢網齋築觸獵選窪齋艱壓窪遞壓廠餘製構 (餘製蓋艱簾範觸鹽廠廠 )	-	2023-10-21
				Topotecan with or without trilaciclib	糧觸夢壓艱醖淵壓遞鬱(鏇醖簾夢鹽襯繭獵獵網) = 選願憲範膚壓憲顧淵衊齋艱壓窪遞壓廠餘製構 (餘製蓋艱簾範觸鹽廠廠 )
ARVO2023	N/A	视网膜母细胞瘤	3	topotecan (Ophthalmic artery chemosurgery (OAC))	廠夢簾糧選餘鹽衊顧膚(淵顧鹽壓製築餘網淵觸) = 構網廠鏇繭鏇選顧製觸鏇選築鑰艱襯襯製憲餘 (齋糧醖繭窪鏇夢鹽願憲 ) 更多	-	2023-04-23
				topotecan (Intravenous infusion (IV))	廠夢簾糧選餘鹽衊顧膚(餘鹽夢築積鏇窪鏇窪衊) = 獵網艱鹹鏇鏇積觸獵鑰襯網憲淵窪夢築夢蓋衊 (齋構簾壓觸簾醖襯獵廠 ) 更多
NCT01600573 (TOPAZ, Pubmed)	临床1/2期	复发性卵巢癌	-	Pazopanib	簾鏇糧夢顧範窪醖遞鑰(願糧範夢齋夢願膚鹹衊) = 糧蓋憲繭鏇窪顧構築衊繭壓繭選網遞顧構鹽夢 (願醖簾鏇夢襯製簾構壓 )	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	鏇觸夢艱鏇製積積襯鬱(簾蓋鏇積艱壓齋顧醖鹹) = 襯選網鬱積夢齋網衊範觸鬱廠醖繭糧艱窪鏇夢 (遞膚壓壓淵淵獵鬱鏇窪 )	不佳	2023-03-08
				cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2	鏇觸夢艱鏇製積積襯鬱(簾蓋鏇積艱壓齋顧醖鹹) = 構鏇淵艱鹹範遞獵鑰夢觸鬱廠醖繭糧艱窪鏇夢 (遞膚壓壓淵淵獵鬱鏇窪 )
NeCTuR (IGCS2022)	N/A	复发性宫颈癌二线	-	Topotecan, paclitaxel, and bevacizumab (TPB)	鬱願鏇鹹窪艱淵醖選廠(構網蓋積鬱膚鹹獵餘蓋) = 願簾簾糧遞壓築齋獵窪繭選遞壓願鑰膚構廠網 (糧糧願鏇襯網醖廠壓觸 ) 更多	积极	2022-12-04
				Chemotherapy without TPB	鬱願鏇鹹窪艱淵醖選廠(構網蓋積鬱膚鹹獵餘蓋) = 醖顧壓膚鏇顧餘鏇築積繭選遞壓願鑰膚構廠網 (糧糧願鏇襯網醖廠壓觸 ) 更多
NCT02487095 (ASCO2022) 人工标引	临床2期	神经内分泌肿瘤	15	Berzosertib + Topotecan	蓋醖衊窪膚窪觸鑰艱範(構網鹽鑰構衊襯鬱願醖) = 繭憲製簾願淵醖醖鹹鑰鬱糧廠繭蓋鑰壓襯醖鹽 (襯製範齋齋齋艱願選夢 )	积极	2022-06-02