Small Cell Carcinoma

©氨基观察-创新药组原创出品作者 | 郑晓为什么中国创新药可以迅速崛起？一个不约而同的答案是：工程师红利。虽然在最“idea”层面可能无法领先，但依靠工程师红利和效率优势，中国药企总能在海外前沿想法的基础上，推陈出新，完成诸多不可思议的突破。过去或许如此，但时移势易，这个答案或许已经不再适用当下。因为中国药企的“脑洞”，越来越大了。在日前的AACR大会上，我们就看到了这样的例子。维立志博的LBL-058，让外媒惊呼中国药企敢于与众不同。LBL-058的“脑洞”大开，它是全球第一个TCE和ADC的结合体：TCE-ADC。简单来说，LBL-058将两项概念结合在一起，由一个靶向DLL3的T细胞接合器与新型拓扑异构酶I抑制剂（TOP1i）有效载荷偶联而成。LBL-058能否成功还不得而知，但它的出现反映了一点，中国创新药企正在力争上游。创新本就是要跳脱既有的条条框框，更加天马行空地引入新奇的想法，务求能达到前人难以企及的高度。从过往来看，大多数科学进步取得重大飞跃背后，也都有着一个鲜为人知的真理：开创性的科学看起来是行不通的，直到它最终被实现或证伪。或许，这也是我们见证中国创新药繁荣的另一个角度，或者说信心的来源。/ 01 /脑洞大开的TCE-ADC任何技术的出圈都不是偶然，而是由其“底层逻辑”决定的。不管是TCE还是ADC的出圈都是如此。TCE的逻辑在于，能够一端与T细胞表面的CD3结合，另一端与目标细胞表面的受体结合，从而将T细胞直接引导至目标细胞附近，激活T细胞对目标细胞的攻击。与常规的IgG相比，TCE被认为比Fc介导的ADCC更有效。这一优势，也使得其在治疗血液瘤、实体瘤以及自身免疫性疾病领域的机会，不断被市场看见。而ADC则有着“魔法子弹”之称，其由抗体、细胞毒素载荷和连接子三部分构成，利用抗体将小分子毒素递送至目标肿瘤细胞内，兼具传统化疗的强大杀伤效应及抗体药物的肿瘤靶向性，实现“精准化疗”的效果。再加上技术的不断升级，ADC在肿瘤领域的竞争力愈发明显。不过，成年人不做选择题。维立志博LBL-058的思路是“我都要”：既要诱导强效的TDCC和T细胞活化，还能选择性地向DLL3阳性肿瘤细胞递送细胞毒性载荷。当然，这两种模式之间需要取得平衡。从构思来看，LBL-058提高了对DLL3的亲和力，降低了对CD3的亲和力，以减少在LBL-058与T细胞结合时有效载荷释放引起的细胞毒性。在此次AACR大会上，维立志博公布的也正是有关验证这一思路的研究，结果显示LBL-058确实更容易与DLL3阳性细胞结合。/ 02 /不能只做跟随者维立志博脑洞大开，也在情理之中。当下，DLL3靶点在小细胞癌的突围，需要的不只是跟随者。虽然小细胞癌的有效疗法稀缺，过去一直依赖于化疗，直到近年来免疫疗法才有所突破，但是，在技术大爆炸时代，免疫疗法的开发已经相当火热。在TCE领域，安进的Tarlatamab已经站稳脚跟。2024年5月，Tarlatamab凭借二期临床DeLLphi-301的数据获得FDA加速批准，99例患者ORR为40%，其中CR为2%，mDoR为9.7个月。Tarlatamab成为首款获批治疗SCLC的靶向免疫类药物，同时也是首款在实体瘤中获批的TCE。最新公布的数据，更是佐证了其战斗力。4月11日，安进宣布Tarlatamab在三期临床中达到OS主要终点，相比于化疗对照组显著延长mOS。在一个适应症获批的情况下，Tarlatamab上市首年（2个季度）销售额已经达到1.15亿美元。目前，其同时开展了二线、一线疗法的头对头实验。如果最终拿出惊艳的结果，无疑可以覆盖更多前线的SCLC患者，对应的护城河也会更稳固。而在ADC市场，包括再鼎医药、信达生物等在内的国内外企业都有所布局，并且取得了积极成果。例如，再鼎医药展现了竞争力，其1a期临床研究数据显示，ZL-1310在所有剂量水平上均表现出抗肿瘤活性，ORR达到了74%，并且安全性良好。由于ZL-1310纳入的所有患者均在接受标准含铂化疗后出现进展，92%的患者在接受免疫检查点抑制剂治疗后出现进展，56%的患者此前至少接受过两种治疗但均失败，即大部分都是末线患者，几乎无药可用。在这一背景下，ZL-1310能够拿出更为可观的数据，无疑值得期待。不管是TCE还是ADC，这些看起来具有前景的领域都已经被竞争对手占据先机，作为后来者自然要思考更多。维立志博的LBL-058在构思方面做了创新，目前其最核心的任务并不是对垒TCE或ADC，而是克服单一DLL3靶向疗法的耐药问题。如果最终临床研究证实其竞争力，那么突围逻辑自然也会更顺畅。/ 03 /见证更多中国“黑科技”LBL-058能否成功还不得而知。毕竟，目前其仅仅只是处于概念验证阶段，距离成药还有十万八千里。然而，不管怎么说，越来越多类似于LBL-058的出现，从另一个维度见证了中国创新药产业的成长。过去，很长一段时间，外界对于我们创新药产业竞争力的认知，都停留在工程师红利这一层面。固然，这一认知并无不妥，工程师红利也极具价值，但是，某种程度上这也意味着我国创新药行业仍需更进一步。过去，我们更多是在跟随他人，但是，所谓创新则必须完成一个不断突破的精进过程，从跟随到超越他人，再到超越自己。而这不能仅仅依靠工程技术的攻坚，更需要理念、思维的碰撞，需要跳脱既有的条条框框，更加天马行空地引入新奇的想法，务求能达到前人难以企及的高度。说白了，一家创新药企到底是“发明家”还是“做题家”非常关键。例如，在ADC热潮中，当国内药企们围绕HER2、Claudin18.2、TROP-2这些热门靶点做同质化研发的时候，同时期的海外Biotech们，已开始针对ADC研发一些可能改变未来的黑科技。而眼下，显然已经截然不同。我们不仅有工程师红利，还足够卷足够努力，一些国内药企也开始跳出舒适圈，带来一些具备奇思妙想的创新。尽管还需要时间的验证，跳出同质化内卷也十分艰难，但是，拓展新技术的道路，本就是布满荆棘与重重困难。与此同时，价值的多少也与挑战的大小，成正比。这也是我们对中国创新药未来更大的期待所在。PS：欢迎扫描下方二维码，添加氨基君微信号交流。

点上方蓝字“ioncology”关注我们，然后点右上角“…”菜单，选择“设为星标”ELCC 2025 微专辑扫描二维码可查看更多内容国际肺癌研究协会（IASLC）与欧洲肿瘤内科学会（ESMO）于2015年联合设立的海因·H·汉森奖（Heine H. Hansen Award），旨在纪念这位丹麦肺癌研究先驱、ESMO与IASLC联合创始人。该奖项每年颁发给为全球肺癌研究与教育作出突出贡献的学者，今年被授予在非小细胞肺癌（NSCLC）分类体系构建及肺癌诊疗指南制定方面有卓越贡献的Keith Kerr教授。Keith Kerr是苏格兰阿伯丁大学医学院和阿伯丁皇家医院的顾问病理学家及病理学教授，专业领域是胸部病理学，尤其是肺癌。他在获奖主题报告中指出：“随着精准医学和人工智能（AI）的发展，肺癌病理学家与临床医生之间长期存在的隔阂正在消弭，病理学分类成果正以创新方式融入临床决策。”祝贺您获得Heine H. Hansen奖。能否分享一下您获奖后的感想，简要介绍获奖主题演讲的核心观点？Dr. Kerr：获得这个奖项对我来说非常荣幸，尤其是作为一名病理学家，能够获得来自肿瘤学术机构（IASLC和ESMO）的奖项意义非凡。多年前我在接受胸部病理学培训时，我的导师就非常明确地指出，除了病理学本身，了解我所研究疾病的临床诊疗也至关重要。我一直努力保持对临床诊疗动态的关注，这对病理学家非常重要。因此，能够获得肿瘤学机构颁发的奖项对我而言意义重大。我的获奖演讲主要强调两个方面。首先是Heine H. Hansen对肺癌及其治疗（尤其是小细胞癌领域）的深远影响。我的年龄足以让我认识他，虽然从未见过他本人，但我会记住他的成果。我的病理学导师与他相识，并密切关注他的研究工作。演讲的另一重点是治疗学发展对近三四十年病理学与诊断技术进步的重要推动作用。尽管病理学家传统上更关注做出诊断，但过去某些诊断并不一定与患者治疗密切相关，然而这种局面在肺癌领域已发生扭转。这正是我职业生涯中见证并希望传递的故事。（上下滑动可查看）Dr Kerr: Well, thank you very much for that. It really is a great honor to receive this award, especially for me as a pathologist to receive an award from an oncology organization is really very special to me. When I was trained a long time ago in thoracic pathology, my mentor was very clear that it was very important for me to be aware of the clinical aspects of the diseases that I was dealing with, as well as the pathology. I have always tried to be clinically aware of what is going on, and I think that is really important for a pathologist. So, it really means a lot to me to get this award from such an organization.I think the key points that I tried to emphasize in my talk accepting the Heine Hansen Award were really two-fold. One was the influence Heine Hansen had on certain aspects of lung cancer and its treatment, particularly in the arena of small cell carcinoma. I am old enough to remember Heine Hansen. I never met him, but I remember him from his work. My pathology teacher knew Heine Hansen and followed his work carefully. The other main point of my talk was how far pathology and diagnostics have evolved over the last 30 or 40 years, largely driven by therapeutics. Although we pathologists tend to concentrate on making a diagnosis, sometimes that diagnosis is not necessarily very relevant for the treatment of the patient, but that has all changed in lung cancer in particular. That is really the story I tried to tell from over the course of my career.您对2025年欧洲肺癌大会（ELCC）哪些讨论和研究最感兴趣？Dr. Kerr：本届ELCC有很多非常精彩的演讲和研究。由于分会场并行，我未能全部参与，但仍注意到几个亮点领域：1.治疗进展：有很多新药和新组合正在涌现，最引人注目的是MARIPOSA研究，其结果显示在EGFR突变NSCLC一线治疗中，埃万妥单抗（amivantamab）联合兰泽替尼（lazertinib）的疗效被证明优于奥希替尼单药，甚至可能优于奥希替尼联合化疗。对EGFR突变NSCLC患者来说，增加了一种新的联合方案，意义重大，尽管其毒性问题引发热议，也有一些临床试验也在探索如何降低毒性。2.人工智能（AI）应用：一些会场探讨了AI将如何影响肺癌治疗的各个方面（包括病理学）。虽然该领域存在炒作成分且资本大量涌入，但人们看到了很多机会。有时，我会担心新技术的快速普及，而我们还没有找到最佳的利用方式。这些新技术真的会对我们有帮助吗？AI看起来会有帮助，可能非常有趣且功能强大，但具体的技术应用路径需进一步探索。3.病理诊断：2025 ELCC的一个会场讨论了诊断服务的问题，以及如何在世界各地（尤其是在资源匮乏的地区）提供诊断服务，尤其是基因分型。我们有时会忽视一个事实：并非每个人都能负担广泛基因检测、高端技术解决方案以及液体活检。这些检测费用昂贵，但提供的信息可能远远超出了治疗患者的实际需求。我有时觉得，尤其是在资源受限的地方，或许资源更应投入在“简单步骤诊断”，因其已能提供大部分必要信息（不是全部）。有时，我们会忽略这种"简约智慧"的价值。（上下滑动可查看）Dr. Kerr: This year at ELCC 2025, there have been lots of very good presentations and studies. Of course, because of our parallel sessions, I haven’t been able to get to everything, but I have attended a few. I think there are 2 or 3 areas that stand out to me for different reasons. In terms of therapeutics, obviously there is a lot going on with new drugs and new combinations coming along. One of the standout discussions at this meeting has been the presentation of the MARIPOSA data where amivantamab and lazertinib have been shown in first-line to be almost superior as a combination to osimertinib in EGFR-mutated tumors, and probably also superior to osimertinib plus chemotherapy. This is a new combination for our EGFR-mutated patients, which is potentially very significant. There are issues with toxicity, and this was the subject of a great deal of discussion and also some clinical trials trying to ameliorate that toxicity. That is one thing. We had a very interesting session on how artificial intelligence is potentially going to impact on all sorts of aspects of lung cancer care, including pathology. There is a lot of hype around this area. There is a lot of investment and money being poured into this. I am sure people see a lot of opportunities. Sometimes I get concerned about the rapid adoption of new technology when we haven’t figured out the best way to use that technology. Is it really going to help us? I does look as if it will, but exactly how that looks remains to be determined, I think. But it is certainly very interesting and potentially very powerful. The last thing, and this is relevant to my area – the issue of delivering diagnostics was discussed in one of the sessions, and how we deliver diagnostics, and especially genotyping, in different parts of the world, especially in parts of the world where there are challenges around resources. I think sometimes we lose sight of the fact that not everyone can afford extensive genotyping, very high-end technology solutions, liquid biopsy testing. These are expensive tests. They often deliver far more information than what is actually required to treat the patient. I sometimes feel, especially in places where resources are constrained, that those resources may be better invested in the simpler diagnostic steps, which still liver most, if not all, of the information that is required for the patient. Sometimes, we lose sight of that simplicity.Heine H. Hansen奖历届得主Enriqueta Felip (2024)Paul Baas (2023)Fred R. Hirsch (2022)Johan Vansteenkiste (2021)Fiona Blackhall (2020)Françoise Mornex (2019)Fabrice Barlesi (2018)Rafal Dziadziuszko (2017)Suresh Senan (2016)Pieter Postmus (2015)《肿瘤瞭望》在ELCC现场报道（来源：《肿瘤瞭望》编辑部）声 明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

HEIDELBERG, Germany, April 15, 2025 /PRNewswire/ -- NEC Laboratories Europe and Data-Driven.AI are working together to enhance medical laboratory diagnosis and increase the effectiveness of preventive health measures and early clinical intervention to improve the well-being of patients. If detected early, many illnesses and diseases can be managed or resolved without serious complications. However, by the time recognizable symptoms present themselves, conditions may already be advanced. In addition, doctors may miss symptoms that call for a specific range of tests to confirm a diagnosis. Giampaolo Pileggi, Project Manager in Biomedical AI at NEC Laboratories Europe, explains, "The human body is incredibly complex, its organ systems working in harmony to keep us healthy. Over time, a minor issue with one system can quickly become serious and affect others." He adds, "Doctors can greatly benefit from AI systems that can uncover hidden correlations in medical data, detecting even the slightest anomalies that may indicate an imbalance in the body. These advanced tools can help physicians to intervene promptly, improving diagnosis and patient care." In regions such as Europe, where age-related illnesses are common, prevention and early-stage intervention are critical to help maintain healthy living and control health services costs. Standard blood tests identify low or elevated levels that may be cause for concern, thus providing clear hints to problematic anomalies, but diagnosing an underlying cause often requires further investigation. NEC Laboratories Europe and Data-Driven.AI are using machine learning to identify unique patterns in blood results that may call for further investigation. Using embedding propagation, NEC technology combines blood analysis information with other patient information to build a condensed representation of their health, which can be used to help predict future patient conditions through additional recommended testing. Diego Facchini, CEO and founder of Data-Driven.AI, says, "As humans, we exhibit characteristic responses to infections, illnesses or imbalances within our bodies, which can be detected through patterns in normal blood values or specific markers found in laboratory diagnostics." He further explains, "The continuous training and refinement of AI models have the potential to revolutionize early disease detection by identifying subtle deviations in a person's health that might be overlooked by traditional methods. By leveraging machine learning algorithms and vast datasets, AI can enhance diagnostic accuracy and improve predictive capabilities, which represent a significant breakthrough in the field of disease detection and prevention." NEC technology's ability to detect subtle nuances in a patient's well-being or current health status has a wide range of potential applications, such as predicting unexpected events in intensive care units and helping diagnose long COVID and the early onset of neurodegenerative diseases such as Parkinson's. About NEC Laboratories Europe NEC Laboratories Europe research and develop cutting-edge technology to create innovative social solutions. Located in Heidelberg, Germany, major research areas of NEC Laboratories Europe include artificial intelligence, blockchain security, 5G and 6G networks, and IoT platforms. These technologies promote NEC Group solutions for a better society in the fields of digital health, safer cities, public services and communication infrastructure. For more information visit . About Data-Driven.AI Data-Driven.AI is a technology company specializing in artificial intelligence and software development, creating innovative solutions that transform data into actionable insights. By leveraging advanced machine learning algorithms, predictive analytics and automation, the company designs and develops AI-driven software applications that optimize business processes, enhance decision-making and unlock new opportunities across industries. With a strong focus on innovation, Data-Driven.AI empowers organizations to harness the full potential of their data, improving efficiency, accuracy and scalability in an increasingly digital world. For more information visit . SOURCE NEC Laboratories Europe GmbH WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED