Serplulimab

点击上方蓝字 关注我们 编者按：国际肺癌研究协会（IASLC）主办的2025年世界肺癌大会（WCLC 2025）于2025年9月6日在西班牙巴塞罗那盛大召开，作为肺癌及其他胸部恶性肿瘤领域全球领先的多学科肿瘤学盛会，WCLC致力于传递领域最前沿进展，为世界各地的专家学者及研究者提供分享前沿研究成果、促进合作交流的平台。近年来，中国创新药在WCLC上频频崭露头角，成为大会备受瞩目的焦点。会议期间，《肿瘤瞭望》在WCLC现场特邀IASLC前任首席执行官、美国纽约西奈山伊坎医学院Fred Hirsch教授；IASLC前任主席、加州大学戴维斯分校综合癌症中心David Gandara教授与复宏汉霖美国首席医学官Ely Benaim博士，围绕肺癌治疗前沿与“中国方案”最新研究展开讨论，本文整理讨论精华内容，以飨读者。 从WCLC重磅进展 看肺癌诊疗最新趋势 Ely Benaim 博士 复宏汉霖美国首席医学官 今年WCLC有哪些研究亮点？这些新研究成果将如何直接影响肺癌的临床实践？ Dr.Ely Benaim: What are the research highlights of this year's World Conference on Lung Cancer(WCLC)? And how will these new findings directly impact clinical practice in lung cancer treatment? Fred Hirsch 教授 IASLC前任首席执行官、美国纽约西奈山伊坎医学院 刚刚结束的首场主席专场（Presidential Symposium）中有多项重要研究成果，首先是对比奥希替尼联合化疗与奥希替尼单药治疗的FLAURA2研究最新数据，先前联合治疗的无进展生存期（PFS）已显示获益，但其总生存期（OS）结果仍待明确。此次公布的数据显示，联合治疗的OS显著优于单药治疗，但也伴随毒性，临床中需充分评估治疗风险。在EGFR靶向治疗领域，随着治疗选择日益丰富和新证据不断涌现，治疗策略排序仍是争论焦点。事实上，基于早前FLAURA2研究的PFS结果，已有不少中心采用联合治疗，此次OS数据发布将进一步支持其应用。 此外，对仅占1-2%的ROS1阳性非小细胞肺癌（NSCLC），靶向新药zidesamtinib公布的数据也显示，它对TKI经治患者仍有44%的较高客观缓解率（ORR），对未接受TKI治疗患者的颅内缓解率为83%；其它一些处于早期开发阶段的新药也值得关注。 Prof.Fred Hirsch: In the first Presidential Symposium that just concluded, a number of studies were highly important. The first key result is from the FLAURA2 study, which compared osimertinib plus chemotherapy with osimertinib monotherapy. While the progression-free survival (PFS) benefit of the combination therapy was already established, the conclusion of overall survival (OS) was still pending. The results released today showed that the combination therapy is indeed superior to monotherapy in terms of OS. Of course, the combination also leads to more toxicities, so the risks need to be fully assessed in practice. I personally believe that how to arrange the most reasonable therapy sequence in EGFR-targeted therapy remains controversial, and with more and more options available, this field is very dynamic. Based on the previous PFS results, many centers were already using the combination therapy, and today's OS data from FLAURA2 study will further support its application. Furthermore, in ROS1-positive patients, whose mutation frequency is only 1-2%, results from the new drug zidesamtinib were also released today. Its highlight is that it showed a high response rate (44%) even in patients who had previously received tyrosine kinase inhibitor (TKI) treatment, and the intracranial response rate in TKI-naive patients was 83%, which is quite impressive. Of course, there are many other promising new drugs in early-stage development. 上下滑动查看英文 David Gandara 教授 IASLC前任主席、加州大学戴维斯分校综合癌症中心 主席专场公布的另一项研究显示，ALK阳性NSCLC患者术后使用克唑替尼，相较仅观察并未展现出更优的疗效，结果初看令人失望；但同一治疗场景中，阿来替尼带来的获益已被明确证实，因此这类研究的意义恰恰在于——通过“退一步”的阴性结果，帮我们更清晰地厘清药物在疾病不同阶段的价值。 除新的治疗策略外，本届WCLC还涵盖多项重要议题，例如Hirsch教授尤为关注的生物标志物研究，以及平台型研究（master protocol）、实用型临床研究（pragmatic protocol）和富集设计（enrichment design）等新型临床研究设计方法。 而在小细胞肺癌（SCLC）领域，我在大会上首次报告了一项以血浆蛋白组学检测将SCLC分为五个亚型的研究，其中仅两个亚型对现有免疫+化疗方案真正敏感，如何基于该分型精准治疗，将是未来的重点探索方向。 Prof.David Gandara: As demonstrated in another study presented during the presidential symposium, postoperative treatment with crizotinib in ALK-positive NSCLC patients did not demonstrate superior efficacy compared to chemotherapy, with initial results appearing disappointing. However, clear benefits of alectinib in this therapeutic setting have already been established. This underscores the critical value of such studies—through "negative findings" from this "step back," we gain crucial insights to better clarify the value of targeted therapies at distinct disease stages. In addition to new therapies, there is a lot of other important information at the WCLC conference, such as biomarkers that Professor Hirsch is most interested in, as well as new clinical trial designs like master protocols, pragmatic protocols, and enrichment designs, among others. And in the field of small cell lung cancer(SCLC), I reported for the first time at this conference on a study that used a plasma proteomics approach to classify SCLC into five subtypes, of which only two truly respond to the existing immunotherapy plus chemotherapy regimen; how to carry out more precise treatment based on this subtyping will be a key area for future consideration. 上下滑动查看英文 聆听肺癌治疗“中国之声” 合力推动国产创新药惠及全球患者 Ely Benaim 博士 复宏汉霖美国首席医学官 让我印象尤为深刻的是，不论是在美国癌症研究协会（AACR）、美国临床肿瘤学会（ASCO）年会还是本次WCLC大会上，我们都看到了大量涌现的中国高质量研究数据报告，且涵盖基础与临床研究，例如复宏汉霖在本次WCLC上展示了有关PD-L1抗体偶联药物（ADC）、EGFR抗体及PD-1抗体（斯鲁利单抗）等研究。两位曾多次到访中国，与众多中国专家进行交流。请问两位如何看待中国研究成果集中涌现？这将产生怎样的影响？  Dr. Ely Benaim: What has particularly impressed me this year is the rapid increase of data from China, which we have seen presented at the annual meetings of the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO), as well as at this WCLC conference. The data, including both basic and clinical research, and the quality of the clinical data is very high. For example, Henlius also presented projects at the conference regarding anti-PD-L1 antibody-drug conjugates (ADC), EGFR antibody, and PD-1 antibody（serplulimab）. Both of you have been to China many times and have interacted with numerous Chinese experts. How do you view this explosion of data, and what kind of impact will it have on treatment? David Gandara 教授 IASLC前任主席、加州大学戴维斯分校综合癌症中心 现在全球癌症治疗最主要的新药来源已是中国，中国不少机构技术进步很快，有最先进的设备和一流的科学家，更关键的是有庞大的患者群体。像此前提到的ALK相关研究，在美国耗时八年完成，而在中国可能仅需两年。新技术、优秀人才与庞大患者资源的结合，催生了大量创新药和临床研究成果，很多甚至来自美国研究者不熟悉的企业。 在2025 ASCO年会上，我主持了名为“i-One”的分会场，当时我甚至把年会称为“中国之年”，因为来自中国的新研究和报告极多，今天在WCLC，我们也看到了许多中国研究成果，这确实开启了新的篇章。 Prof.David Gandara: Currently, the main source of new drugs for cancer treatment worldwide is already China. Many research centers in China are making very rapid technological progress, possessing the most advanced equipment and first-class scientists. More importantly, China has a huge patient population. For example, the previously mentioned study of ALK-positive patients took eight years to complete in the United States, while the same study, if conducted in China, might only take two years to complete. Combining new technologies, excellent talent, and a large patient population will lead to the emergence of a large number of innovative drugs and clinical research results, many of which are from companies that American researchers are not even familiar with yet. At the recent 2025 ASCO annual meeting, I chaired a session called "i-One." At that time, I even referred to ASCO 2025 as the “Year of China” because there were simply too many new studies and reports from China. And today at WCLC, we also saw many research findings from China, which indeed is a new day, a new awakening. 上下滑动查看英文 Fred Hirsch 教授 IASLC前任首席执行官、美国纽约西奈山伊坎医学院 当前中国在药物研发和生物技术方面的发展确实令人瞩目，但也带来了一些挑战，其中最大的挑战在监管层面。例如我们希望看到中国研究在西方人群中得到验证，但这类研究往往耗时数年，所以后续应重点关注监管如何应对新药新研究的涌现，且美国FDA和欧洲EMA都应积极参与。从患者角度来看，肺癌治疗虽已进展显著，但仍迫切需要新药、新疗法和新技术，尽早用上能精准匹配需求的治疗，监管必须跟上这样的快速发展。我们已计划召开一系列汇聚各方代表的会议，坦诚探讨监管在新形势下的定位，以及如何适应并推动发展。 Prof.Fred Hirsch: The current development of China in drug research and biotechnology is indeed very impressive, but it also brings some challenges, the biggest of which is undoubtedly at the regulatory level. For example, we hope to see Chinese trials validated in Western populations, but such clinical trials often take many years to finish. Therefore, the next issue that needs to be focused on is how the regulatory system should respond to this surge of new drugs and new research, both the FDA and EMA should be involved. From the patient's perspective, even though significant progress has been made in the field of lung cancer, the patient's need for new drugs, new therapies, and new technologies is still very urgent, especially for treatments that can be accessed early and matched to the right patients. Therefore, the regulatory system must keep pace with this rapid development. We have already planned to convene some meetings, hoping to bring all parties together to openly discuss the position of regulation and how to adapt to and promote the current exciting pace of development. David Gandara 教授 IASLC前任主席、加州大学戴维斯分校综合癌症中心 创新药要获得FDA批准，通常需提供西方人群数据，过去，甚至可能要求中国企业重新开展临床研究。但是至少在我参与的ASTRIDE等研究中，情况已有所不同。FDA态度相当务实，认可在中国完成且疗效出色的ASTRUM研究，仅要求提供斯鲁利单抗在美国人群中的疗效和安全性与中国数据一致的证据，即允许通过“桥接研究”满足监管要求，ASTRIDE研究正是这样的研究。此外，斯鲁利单抗也已获欧洲EMA批准上市，这些都反映出监管思路的更新，能让创新药更快进入美国市场，让患者更早获益，对整个领域也是积极的改变。 同时，ASTRIDE研究旨在证明斯鲁利单抗疗效和毒性与现有药物相当，那么临床医生为何要选斯鲁利单抗，而不是更熟悉的同类药物？毒性更低、疗效更好，或为特定患者带来更多获益，才是选择它的理由，这正是ASTRIDE研究的价值：虽然它是一项桥接研究，但也融入了一些极具意义的分子层面分析，比如之前提到以血浆蛋白组学检测，预测SCLC患者的获益可能，即PROFIT SCLC检测，如检测结果为阳性，患者就适用斯鲁利单抗，从而真正带来新的治疗机会。 Prof.David Gandara: For an innovative drug to gain FDA approval in the U.S., it has typically needed to provide data from Western populations, and previously, Chinese companies would even be asked to completely re-conduct their clinical studies. However, in at least some of the studies I have participated in, such as the ASTRIDE study, the situation has already been different. The FDA's attitude is quite pragmatic, recognizing the ASTRUM study, which was completed in China and showed excellent efficacy. It only required evidence that the efficacy and safety of serplulimab in the American population are consistent with the Chinese data, allowing us to use so-called “bridging studies” to meet regulatory requirements. We are currently conducting such a study. Furthermore, serplulimab has already been approved by the EMA in Europe. All of this reflects an updated regulatory mindset, allowing innovative drugs to enter the U.S. market more quickly, benefiting patients sooner. This is a positive change for the entire field. In the mean time, the ASTRIDE study is designed to prove that serplulimab is comparable to existing drugs in both efficacy and toxicity, but what does this mean for its application in Europe or the U.S.? The key lies in the details of the study. Why would a clinician choose serplulimab over a more familiar drug of the same class? The reasons for selecting it would be lower toxicity, better efficacy, or greater benefit for specific patients. This is precisely where the value of the ASTRIDE study lies. Although it is a bridging study, it also incorporates some very meaningful molecular-level analyses, such as the plasma proteomics test mentioned earlier, which predicts the likelihood of benefit from immunotherapy for SCLC patients, we call it the PROFIT SCLC test. With this test, we can tell clinicians that if a patient's test result is positive, serplulimab is suitable for them, which truly provides a new treatment opportunity for these patients. 上下滑动查看英文 Ely Benaim 博士 复宏汉霖美国首席医学官 我同意，这也是我与FDA打交道时的体会，例如对全球多中心试验，FDA会要求美国患者占比达10-30%，类似ASTRIDE研究证明创新药在美国人群中的疗效和安全性，继而进入审批讨论流程，但我认为这一流程需继续加快。尽管肺癌治疗已取得巨大进步，晚期肺癌仍无法真正治愈，患者依然存在迫切治疗需求，而我们的最终目标，至少是将肺癌转变为一种可长期控制的慢性病，类似当前的大多数乳腺癌。 因此，我认为当前来自中国的临床研究热潮，至少能在I/II期研究层面发挥重要作用。例如，一项入组40例患者的单臂研究或小规模随机对照试验，6个月就能完成并读出结果，在过去几乎不可想象，同时也能让我们在进入审批流程前，更快速清晰地明确下一步方向。FDA重视并逐步认可中国数据，核心关切仍是这些研究是否适用于美国人群。 Dr.Ely Benaim: This is also my experience with the FDA. For example, in global multi-center trials, the FDA will require the proportion of American patients to be 10-30%, enrolling American patients just like in the ASTRIDE study. This serves to prove that the efficacy and safety of the innovative drug in the American population are consistent with the Chinese data, and then the approval discussion process begins, but I believe the process still needs to be accelerated. As mentioned before, while great progress has been made in lung cancer treatment, advanced lung cancer still cannot be truly cured, and patients continue to have an urgent need for treatment. Our ultimate goal is at least to turn lung cancer into a chronic disease that can be controlled long-term, just like most breast cancers now. Therefore, I believe this wave of clinical research from China can at least play a significant role in promoting Phase I/II studies. For example, a single-arm study or a small-scale randomized controlled trial enrolling 40 patients could be completed and have its results read out in just 6 months, which was almost impossible in the past. This also allows us to know the next steps more quickly and clearly before entering the approval discussion process. Currently, the FDA is indeed looking seriously and accepting data from China, but it also wants to ensure that the study conclusions are applicable to the American population. 上下滑动查看英文 聚焦在研ADC新星 看后起之秀发力改写诊疗格局 Ely Benaim 博士 复宏汉霖美国首席医学官 Hirsch教授，作为PD-L1 ADC药物HLX43美国临床研究的主要研究者（PI），您能否从ADC药物在肺癌治疗中的发展脉络出发，阐释HLX43的独特机制与定位？纵观ADC药物从过去有限的角色到如今成为治疗支柱的变迁，您认为HLX43未来将如何重塑NSCLC治疗格局？ Dr. Ely Benaim: Professor Hirsch, you are the principal investigator (PI) for the U.S. portion of our other clinical study evaluating the anti-PD-L1 ADC drug, HLX43. Could you explain the unique mechanism of HLX43 and its positioning, starting from the developmental trajectory of ADC drugs in lung cancer treatment? Looking at the transformation of ADC drugs from their limited role in the past to becoming a pillar of treatment today, how do you think HLX43 will reshape the NSCLC treatment landscape in the future? Fred Hirsch 教授 IASLC前任首席执行官、美国纽约西奈山伊坎医学院 目前，ADC药物的研发进展迅速，部分新型ADC在临床中展现出令人鼓舞的疗效。然而，现有的PD-1/L1抗体疗法仍存在明显局限——仅有约40%的患者能够从中明确获益，其余患者则出现初始无应答或继发性耐药，治疗需求远未满足。因此，开发新型靶向PD-1/L1的药物显得尤为迫切。另一方面，肺鳞癌与非鳞癌在生物学行为上存在显著差异，这种差异如何影响免疫治疗的效果，仍需深入探索；同时也要求新一代PD-1/L1靶向药物对鳞癌患者具备更强的疗效。基于现有早期数据，靶向PD-L1的ADC药物HLX43在上述两个方向都表现出良好的潜力，值得进一步关注与研究。 总体而言，ADC发展极具前景也充满挑战。约一个月前我在《Clinical Cancer Research》上发表的评论文章就特别强调了这一点。ADC的靶点选择多样，有些ADC的靶点由基因突变驱动，有些则由蛋白过表达或拷贝数改变驱动。虽然靶向驱动基因本身可以有效抑制肿瘤生长，如靶向EGFR突变的TKI药物，但ADC药物的作用机制不同，这要回到其基本作用机制：ADC的起效依赖于抗体能否精准结合细胞表面蛋白，连接子及载荷毒素能否有效内化进入细胞，以及高效毒素的杀伤，以上三个关键环节仍有优化空间，而我认为HLX43在各个环节均有改进，有望进一步推动现有成果迈向更深层次的发展。 Prof. Fred Hirsch: The research and development of ADCs is currently progressing quickly, and the efficacy data of some new ADC drugs is very encouraging. We indeed need new drugs to assist existing PD-1/L1 antibodies, because only about 40% of patients can obtain clear clinical benefits from current treatments. Other patients either do not respond or develop resistance, and the treatment plans for these patients are still undecided, which is also an important area that needs new PD-1/L1-targeted drugs. In addition, the biological behavior of squamous cell carcinoma is significantly different from that of non-squamous cell carcinoma, We still need a deeper understanding of how this difference impacts immunotherapy, and new PD-1/L1-targeted drugs also need to be more effective for patients with squamous cell carcinoma. Based on the preliminary data, HLX43, a PD-L1-targeted ADC, has great potential in both above-mentioned areas, and we need to follow its development. Overall, ADC is a very promising direction for development, but it is also full of challenges. A review article I published in Clinical Cancer Research about a month ago also specifically mentioned this point. We know that the selection of targets for ADCs is highly diverse. Some ADC targets are driven by genetic mutations, while others are driven by protein overexpression or copy number alterations. Although targeting the driver gene itself can effectively inhibit tumor growth—as seen with TKIs targeting EGFR mutations—the mechanism of action of ADC drugs is different, which brings us back to their fundamental mode of action: the mechanism of action of ADCs involves three key parts. First, whether the antibody can accurately bind to the cell surface protein; second, whether the linker and the drug can successfully enter the cell; and third, an effective payload of toxins. All three of these parts still have room for optimization. I personally believe that HLX43 has been optimized and improved in all three of the above-mentioned aspects, and therefore, I believe it has the potential to further advance the existing achievements to a deeper level. 上下滑动查看英文 David Gandara 教授 IASLC前任主席、加州大学戴维斯分校综合癌症中心 我还想补充一点，约两年前ADC还被认为前景广阔，但如今热度有所回落，原因是当时出现了一批所谓“不限癌种（tumor-agnostic）”ADC，但其中许多都已失败，如靶向CEACAM5、HER3及部分TROP家族靶点的ADC，其中的启示就是——“靶点选择至关重要”，也解释了为何PD-L1是理想的ADC靶点，上百项研究都证实过它的重要性。我们必须回归ADC设计的原点，即靶向肿瘤特异性靶点，而我也非常期待HLX43后续研究结果。 Prof.David Gandara: I'd also like to add something: about two years ago, the prospects for ADC drugs were considered extremely broad, but now the enthusiasm has somewhat decreased. The reason is that a group of so-called "tumor-agnostic" ADCs appeared at that time. However, many of these drugs, such as ADCs targeting CEACAM5, HER3, and some TROP family targets, failed. This taught us that "the target is very important," which is also why PD-L1 is a suitable ADC target. Over 100 studies have now proven that PD-L1 is an extremely important target, so we must also return to the origin of ADC design, which is to target tumor-specific targets. I am also very much looking forward to the results of the subsequent related studies on HLX43. Ely Benaim 博士 复宏汉霖美国首席医学官 最令我印象深刻的是HLX43设计上的突破，如药物-抗体比高（DAR）、效能强大、能被癌细胞快速内吞，且系统性毒性较低。这些创新靶点明确、递送精准，未来很可能彻底改变我们对ADC的认知，带来真正的治疗新希望。 Dr.Ely Benaim: For me, what's most impressive is the breakthrough in its design. For example, HLX43 has a very high drug-to-antibody ratio (DAR), has high potency, and can be rapidly internalized by cancer cells, yet it has very low systemic toxicity. The design of these innovations have clear targets and precise drug delivery, and they are likely to change our perception of ADCs in the future, bringing genuine new hope for treatment. 从AI赋能到量身定制 展望未来肺癌精准治疗 Ely Benaim 博士 复宏汉霖美国首席医学官 如果五年后我们还在这里交流，届时肺癌治疗的新进展和新成果会是什么？虽然目前热议的是个体化治疗、靶向治疗等课题，但还有很多未被充分讨论的方向，如人工智能（AI）在临床试验设计和新药研发中的应用。两位认为未来肺癌治疗领域的发展方向会是什么？ Dr.Ely Benaim: If we were to meet here in five years, what new developments and achievements would we be discussing? While topics like personalized medicine and targeted therapy are currently being widely discussed, there are actually many other directions we haven't touched on, such as the application of artificial intelligence (AI) in clinical trial design and new drug R&D. What do you both believe the true direction of future development will be? Fred Hirsch 教授 IASLC前任首席执行官、美国纽约西奈山伊坎医学院 以SCLC为例，它的生物学行为与NSCLC存在显著差异，且本身具有高度异质性，例如不同共突变可能影响治疗效果。随着对相关机制的理解不断深入，我们也愈发认识到SCLC的复杂性。因此我们需更深入了解肿瘤的生物学本质，进一步研究生物标志物，并探索基于标志物制定治疗方案。也许五年后，我们就将进入“联合治疗”的新时代，即基于科学依据和生物学行为，通过严谨设计将多种治疗合理组合。 Prof.Fred Hirsch: Take SCLC for example, its biological behavior is significantly different from NSCLC, and it is highly heterogeneous itself, as different co-mutations can affect treatment. As our understanding of it deepens, the complexity of SCLC also increases. We still need a deeper understanding of the biological nature of tumors, to further study biomarkers, and to explore how to formulate treatment plans based on them. Perhaps in five years, we'll enter a new era of "combination therapy"—that is, a rational combination of multiple treatments, rigorously designed based on scientific evidence and biological behavior. David Gandara 教授 IASLC前任主席、加州大学戴维斯分校综合癌症中心 我认为未来五年最重要的方向，是比当前更深入的个体化治疗，过去我们曾用“精准肿瘤学”、“个体化治疗”等名字，但对患者而言，最重要的是被医生视为独立的个体，而不是“百分之一”，只有这样才可能使不同患者获得完全不同的治疗。 下周我将在美国西南肿瘤协作组（SWOG）大会做主题报告，回顾过去二十年肺癌领域的变迁。二十年前，我们只有针对EGFR靶点的药物，而到去年12月，指南要求检测11个致癌基因，这意味着什么？如果我们广泛检测，就像撒下一张大网，可以捕到很多“鱼”；如果只做有限检测，就如同小网捕鱼，收效甚微。例如检测EGFR突变时，就可能意外发现ROS1突变——上周我就有这样一例患者，意外发现的基因突变彻底改变了治疗。为每一位患者量身定制治疗，才是未来真正的方向。 Prof.David Gandara: I believe the most important direction for the next five years is personalized therapy, and it will be even more in-depth than it is today. We previously used names like "precision oncology" and "individualized therapy" to refer to it. But for the patient, the most important thing is that when they see a doctor, they hope the doctor will consider them as a unique individual, not just "one of a hundred," which is the only way for different patients to receive completely different treatment plans. Next week, I will be speaking in the plenary session at the Southwest Oncology Group (SWOG) conference, reviewing the changes in the field of lung cancer over the past twenty years. First, I will look back at twenty years ago, when only targeted drugs for one target, EGFR, were available. By last December, according to the guidelines, we already needed to test for 11 oncogenes. What does this mean? If we test broadly, it's like casting a wide net and we can catch many "fish"; if we only do limited testing, it's like fishing with a small net, and the returns are minimal. For example, when testing for EGFR, we might incidentally discover a ROS1 mutation with a frequency of only 1%. I had one such patient last week; the accidental discovery of another gene mutation completely changed his treatment plan. Therefore, personalized therapy for each individual patient is the true direction of future development. 上下滑动查看英文 Ely Benaim 博士 复宏汉霖美国首席医学官 谈到联合治疗，我首先考虑的是安全性，因其往往受限于过高的毒性。在当前临床研发中，利用机器学习和AI，基于药物结构预测毒性的做法越来越普遍。事实上，我们已经积累了海量数据——数百万接受过不同药物治疗的患者，现有数据规模足以支持新工具在药物进入人体试验前，预测潜在可行的联合方案。 因此我认为，机器学习必将对未来癌症治疗产生重大影响。它不仅能辅助分析现有药物的真实世界证据，还可基于已知的毒性和疗效模式设计新药，在临床试验前预测出许多问题。复宏汉霖已在很多研发环节尝试应用人工智能，许多企业也在做类似探索。二位认为机器学习和AI将如何推动新药临床研发？ Dr.Ely Benaim: Your comments make me think that throughout our education and professional training, we have always placed a strong emphasis on biological characteristics, as well as on evidence and data. For example, when combination therapy is mentioned, the first thing I think of is safety, because the limitation of combination therapy is often its excessive toxicity. A practice that is becoming more common in the clinical R&D field is to use machine learning and artificial intelligence to predict toxicity based on drug structure. In fact, we have already accumulated a large amount of data—millions of patients have been receiving various different drug treatments. The amount of data is now large enough that new tools can predict which potential drug combinations are feasible before the drugs even enter human trials. So in my opinion, machine learning will definitely have a big impact on cancer treatment in the future. It can not only help us analyze the real-world evidence of existing drugs, but also design new drugs based on existing toxicity and efficacy patterns, allowing many problems to be predicted before clinical trials. Our company is now trying to apply artificial intelligence in many stages of R&D, and many companies are doing similar things. So, how do you think machine learning and AI will help in the clinical R&D of new drugs? 上下滑动查看英文 Fred Hirsch 教授 IASLC前任首席执行官、美国纽约西奈山伊坎医学院 在预测毒性及寻找毒性相关生物标志物方面，我们长期以来一直面临着数据不足，但如今有着海量数据和诸多数据收集机会，完全可能借助机器学习和AI来预测毒性。ADC药物有毒性，联合疗法中使用的药物也各有毒性，毒性问题是必须要应对的挑战，需要相应制定合理的联合治疗方案、预测毒性，并最终实现毒性的预防。 Prof.Fred Hirsch: When it comes to predicting toxicity and finding toxicity-related biomarkers, we've actually always lacked sufficient data. But now we really have a massive amount of data and many opportunities for data collection, so it's entirely possible to use machine learning and AI to predict toxicity. Toxicity is a very significant problem—for example, the toxicity of the ADC drugs we discussed earlier, and of course, the drugs used in combination therapy each have their own toxicity, and that's a challenge we have to face. We need to learn how to formulate right drug combinations, predict toxicity, and even achieve toxicity prevention. David Gandara 教授 IASLC前任主席、加州大学戴维斯分校综合癌症中心 目前关于AI仍有许多争议，有人认为它会是救星，也有人担心负面影响，关键在于如何运用。在肿瘤学领域，AI或机器学习可分析数千个潜在新靶点（包括蛋白或基因突变），进而筛选出其中十个最具研发前景的靶点——这正体现了AI的价值。 我举一个实例：我在本次大会上关于SCLC分型的报告，完全基于机器学习完成。我们团队分析了血液循环中的7000种蛋白质，研究了它们的生物学功能和与SCLC的关系，最终建立了一个分子分型体系。结合患者数据后，我们发现不同分型患者的生存期确实存在差异，并且仅有少数分型对免疫治疗真正产生应答。我认为，这样才是未来：有方向、有指导地审慎使用AI而非随意滥用，才能更快速、更有效地推动研究，让治疗早日惠及患者。 Prof.David Gandara: I think there's still a lot of controversy when it comes to AI. Some people think it'll be our savior, while others worry about its negative impacts. The key is how we use it. In oncology, an AI or machine learning program might analyze thousands of potential new targets, including proteins or gene mutations, and then screen out the ten most promising ones to advance. That's the value of AI. I'll give you a practical example: my report on SCLC subtyping at this WCLC conference was conducted entirely using machine learning. Our team analyzed 7,000 proteins in blood circulation, studied their biological functions and the relationship between those functions and small cell lung cancer. We eventually established a molecular subtyping system, and then combined with patient data, we found that different subtypes do have differences in survival, and only a few subtypes truly respond to immunotherapy. In my opinion, this is the future: using AI in a directed and guided way, not arbitrarily. Only then can it help us advance research faster and better, allowing treatment to benefit patients sooner. 上下滑动查看英文 Fred Hirsch IASLC前任首席执行官、美国纽约西奈山伊坎医学院 西奈山Tisch癌症研究所(TCI)胸部肿瘤中心执行主任，TCI生物标志物发现部副主任。Hirsch曾在科罗拉多大学担任医学和病理学教授18年，并曾担任国际肺癌研究协会(IASLC)首席执行官。 David Gandara IASLC前任主席、加州大学戴维斯分校综合癌症中心 国际液体活检协会首席医疗官 加州大学戴维斯分校综合癌症中心主任高级顾问 夏威夷大学癌症中心转化与临床研究项目兼职临床教授、名誉教授 国际肺癌研究协会(IASLC)前主席 Ely Benaim 复宏汉霖美国首席医学官 全面负责复宏汉霖美国的临床医学研发等相关事务，作为美国市场的医学负责人，他同时支持复宏汉霖的研发和商务拓展等相关事宜。 Ely Benaim博士在委内瑞拉中央大学获得医学博士学位，曾在田纳西大学儿科系担任副教授，并曾在Amgen, Takeda Oncology, Berg, Rexahn Pharmaceuticals, Novocure, SonALAsense等公司担任首席医学官或其他重要职位。他在科学和医学领域拥有超过25年的工作经验，其中包括在生物制药行业的17年工作经验。 （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。