Crizotinib

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。

多元化新药的发展促就了当下时代肺癌领域的万象新生，本届的WCLC，让我们在享受部分经典研究带来的疗效震撼外，也不断接受来自新型药物新型治疗模式的洗礼冲击，BIG简要整理，以飨同仁，共同跟上全球肺癌的研究步伐。 目录： 非小细胞肺癌  晚期  1. III期FLAURA2研究：奥希替尼靶化联合一线OS重磅面世，获益显著！  2. ACROSS2研究：阿美替尼联合化疗挑战EGFR合并伴随突变肺癌一线获佳绩！  3. EGFR突变晚期NSCLC一线方案讨论  4. HARMONI研究：双抗Ivonescimab+化疗对比单纯化疗治疗TKI耐药后EGFR突变肺癌获佳绩。  5. COMPEL：奥希替尼联合含铂化疗治疗一线奥希耐药的脑部未进展的肺癌  6. ARROS-1研究：新一代ROS1抑制剂Zidesamtinib  7. PDL1ADC HLX43 I期结果出炉，ORR46.7%！  8. TROPION-Lung01研究：Dato-DXd颅内疗效确切，CNS cORR 38%！  9. E4512：克唑替尼术后辅助ALK+肺癌，获阴？  10. NAUTIKA1研究：阿来替尼围手术期处理ALK+肺癌，MPR 60.7%  11. ALK耐药机制研究  12. KRAS G12C抑制剂olomorasib联合化免一线治疗KRASG12C突变肺癌，ORR 50~68%  13. GFH375治疗KAS G12D肺癌，有效率57.7%。  14. 肺癌双抗的探讨  15. HER2靶点  16. EGFR/HER3双抗ADC BL-B01D1治疗晚期实体瘤，初显疗效！  17. PRMT5抑制剂BMS-986504 初步结果，肺癌有效率29%，TP53突变41%ORR。  18.双抗ADC BL-B01D01+奥希替尼治疗EGFR突变肺癌，ORR100%！ 围手术期  1. NADIM ADJUVANT研究：O药+化疗早期NSCLC术后辅助模式III期告捷！  2. Checkmate816研究OS结果更新  3. AEGEAN研究：度伐利尤单抗围手术期处理复发进展结果更新  4. RATIONALE-315研究：替雷利珠单抗围手术期处理OS结果获阳！  5. Keynote671研究：K药围手术期治疗NSCLC，4年疗效更新（结阴：结阳）  6. STAS（气腔内播散）在IA期肺癌的预后价值  7. NADIM研究，化免围手术期处理模式对手术的影响  8. 早期肺癌：VATS PK 开放手术，孰更优？  9. NeoADAURA研究：MRD分析显示ctDNA可作为新辅助治疗的预后因素  10. SKYSCRAPER-05研究：TIGIT抑制剂tiragolumab联合T药±化疗围手术期治疗II-IIIB期NSCLC。  局晚期  1. 特瑞普利单抗+化疗术前诱导不可手术局晚期NSCLC，手术转化率高！  2. EA5181研究：I药同步放化+免疫巩固对比单纯免疫巩固，未见疗效提升？PACIFIC模式仍是标准。  3. 局晚期SCLC：大分割放疗 PK 常规分割，未达到非劣效终点  4. III期NSCLC汇总性图片  小细胞肺癌  1. SEZ6：SCLC新晋明星靶点  2. IDeate-Lung01研究：B7H3 ADC药物I-Dxd治疗SCLC II期结果坚挺！  3. DeLLphi-303研究：tarlatamab联合EP冲击ES-SCLC一线OS达25.3个月。   CD3/DLL3 BITE类药物tarlamab继获批SCLC二线治疗后，本次携一线数据强势亮相，在初治广泛期SCLC中，进行4~6周期的tarlatamab联合EP化免治疗后，采用tarlatamab+阿替利珠单抗/度伐利尤单抗维持治疗，结果显示，中位OS达到25.3个月，中位PFS为5.3个月，ORR29%。基于此，III期DeLLphi-305研究正在开展中。  4. DLL3 ADC SHR4849治疗复发SCLC初步疗效优秀！  5. PDL1/VEGF-A双抗BNT327联合化疗一线治疗ES-SCLC，uORR 86.8%。  6. II研究：特瑞普利单抗用于同步放化疗后未进展的局晚期SCLC的巩固治疗  7. 卡瑞利珠单抗探索局晚同步放化疗夹心治疗模式初显疗效  8. 广泛期SCLC的免疫治疗对比  9. 局晚期SCLC目前正在开展的关键III期临床研究  间皮瘤    01   非小细胞肺癌   晚期   1.III期FLAURA2研究：奥希替尼靶化联合一线OS重磅面世，获益显著！ 奥希替尼单药在创造了晚期EGFR敏感突变的非小细胞肺癌一线疗效新高度后，继续升级探索，通过与AC方案联合（4周期后奥希替尼+培美曲塞维持治疗）对比奥希替尼单药，III期FLAURA2在2023年已报道主要终点PFS的成功（25.5：16.7个月，HR=0.62），时隔2年后，最具临床意义的III期OS结果尘埃落定，以47.5：37.6个月，HR=0.77，P=0.02的绝对统计学优势和临床差异证明了靶化联合在EGFR敏感突变晚期肺癌一线的绝对地位，成就了新的一线标准。各亚组人群均呈获益趋势，且靶化联合组药物暴露分析显示化疗仅使用了较短的时间（中位暴露8.3个月）。该研究的成功一度引爆了与会现场的激烈讨论，也引发了对于晚期EGFR突变肺癌一线的方案（MARIPOSA研究埃万妥单抗联合拉泽替尼， OS HR=0.75（NEJM同步发文）；AENESA2研究阿美替尼联合化疗，OS未成熟 初步HR=0.44 ）对比讨论见标题3。 2.ACROSS2研究：阿美替尼联合化疗挑战EGFR合并伴随突变肺癌一线获佳绩！ 国产三代EGFR-TKI阿美替尼此次大会也带来了亮眼的研究探索，联合AC化疗一线治疗EGFR敏感突变同时伴随替他突变（TSG）的晚期NSCLC，结果显示，对比单纯靶向，主要终点研究者评估的PFS分别为19.8：16.5个月，HR=0.55，OS目前尚不成熟。靶化联合能明显提升疗效，但也不难看出，这类伴随突变的人群整体PFS相比其他混合人群的PFS有所下降，此类人群对于强化治疗的需求明确。 3.EGFR突变晚期NSCLC一线方案讨论 4.HARMONI研究：双抗Ivonescimab+化疗对比单纯化疗治疗TKI耐药后EGFR突变肺癌获佳绩。 Ivonescimab是一款PD1/VEGFR双抗，联合化疗挑战EGFR突变肺癌靶向耐药后的二线治疗，结果显示，相比传统单纯化疗，主要终点PFS 6.8：4.4个月，HR=0.52，P<0.00001，获得阳性结果，另一联合终点OS亦有获益趋势（16.8：14.0个月，HR=0.79，P=0.057），为EGFR突变二线提出新的化疗加持模式，也引发了学者对于靶向耐药后二线新治疗方案（MARIPOSA-2研究：埃万妥单抗联合化疗；HERTHENA-Lung02研究：HER3 ADC药物Patritumab）以及免疫+化疗+抗血管三联方案的对比讨论。 COMPEL：奥希替尼联合含铂化疗治疗一线奥希耐药的无转移肺癌 5、COMPEL：奥希替尼联合含铂化疗治疗一线奥希耐药的无转移肺癌 相比仅进行单纯化疗，PFS及OS均有获益，提示奥希替尼耐药后持续使用的价值。 ARROS-1研究：新一代ROS1抑制剂Zidesamtinib A 6.ARROS-1研究：新一代ROS1抑制剂Zidesamtinib。 总体疗效44%，处治疗效89%，对于G2032R难治耐药突变疗效54%，为ROS1提供新一代治疗药物。 7.PDL1ADC HLX43 I期结果出炉，ORR46.7%！ PDL1单抗HLX43 I期结果出炉，ORR46.7%！ 8、TROPION-Lung01研究：Dato-DXd颅内疗效确切，CNS cORR 38%！ TROPION-Lung01研究：Dato-DXd颅内疗效确切，CNS cORR 38%！ E4512：克唑替尼术后辅助ALK+肺癌，获阴？ 9、E4512：克唑替尼术后辅助ALK+肺癌，获阴？ 阿来替尼基于ALINA研究（DFS HR 0.24）确立了ALK TKI在术后辅助的地位，但克唑替尼的E4512研究结果显示在DFS和OS上均未显示出阳性结果，这让很多学者诧异，也有学者尝试分析其失败原因。 10.NAUTIKA1研究：阿来替尼围手术期处理ALK+肺癌，MPR 60.7%。 NAUTIKA1研究：阿来替尼围手术期处理ALK+肺癌，MPR 60.7% ALK耐药机制研究 11、 ALK耐药机制研究 两点有意思的发现：相比克唑替尼耐药后使用下一代TKI，直接使用下一代TKI获得性突变发生频率更低。MET扩增是ALK耐药后最常见的脱靶性突变类型。 12、KRAS G12C抑制剂olomorasib联合化免一线治疗KRASG12C突变肺癌，ORR 50~68% KRAS G12C抑制剂olomorasib联合化免一线治疗KRASG12C突变肺癌，ORR 50~68% 13、GFH375治疗KAS G12D肺癌，有效率57.7%。 GFH375治疗KAS G12D肺癌，有效率57.7%。 肺癌双抗的探讨 HER2靶点 15、HER2靶点 HER2突变在NSCLC的发生率为2-4%，T-DM1被批注作为二线治疗，其他药物如savebertinib（BAY 2927088）及zongertinib正在探索中。此次一款HER2 ADC药物TQB2102疗效公布，结果显示，在37里HER2突变患者中ORR为61%，在11例HER2扩增或蛋白过表达的患者中，有效率为44.4%，在11例同时具有HER2异常及EGFR突变的患者中，ORR为100%。 2.EGFR/HER3双抗ADC BL-B01D1治疗晚期实体瘤，初显疗效ORR 66%！ 16、EGFR/HER3双抗ADC BL-B01D1治疗晚期实体瘤，初显疗效！ BL-B01D1是一项EGFR/HER3双抗ADC，毒素为DNA拓扑异构酶（Ed-04），在本次公布的数据中，整体ORR为57.9%，mPFS为6.9个月，mOS为24.8个月。在3代TKI进展后未进行化疗的患者中，ORR为65.2%，mPFS为12.5个月，mOS尚未达到，为EGFR突变肺癌带来新的药物类型。可期。 17、PRMT5抑制剂BMS-986504 初步结果，肺癌有效率29%，TP53突变41%ORR。 PRMT5抑制剂BMS-986504 初步结果，肺癌有效率29%，TP53突变41%ORR。 18.双抗ADC BL-B01D01+奥希替尼治疗EGFR突变肺癌，ORR100%！   围手术期   1、NADIM ADJUVANT研究：O药+化疗早期NSCLC术后辅助模式III期告捷！ 本次O药在早期可切除肺癌（IB-IIIA）R0切除后的术后辅助中，探索了一种新的辅助治疗模式，术后进行O药+化疗4周期辅助治疗后，后续O药6周期维持治疗，相比传统仅进行化疗4周期辅助化疗，主要终点DFS 虽尚未达到，但36个月的DFS率显著提升（73.3%：59.9%，HR=0.65，P=0.085），敏感性分析亦支持。 围手术期的研究对比 Checkmate816研究OS结果更新 2、Checkmate816研究OS结果更新 CheckMate -816研究开创了化免联合（O药+含铂化疗）作为新辅助治疗方案，用于可切除（肿瘤≥4厘米或淋巴结阳性）NSCLC的治疗模式，主要终点pCR（24%：4.6%）和EFS（54.8：20.9个月）均显著提升，年初报道了OS结果（HR 0.72），依然获得了统计学意义和临床意义的改善。此次大会对OS结果进行了亚组分析，获益趋势相似，但需注意的是，对于R1切除的患者未有提升，需谨慎选择，为未来其他研究的开展提供人群参考。 AEGEAN研究：度伐利尤单抗围手术期处理复发进展结果更新 3、AEGEAN研究：度伐利尤单抗围手术期处理复发进展结果更新 AEGEAN研究模式是术前4 周期新辅助度伐利尤单抗 + 含铂化疗，术后进行 12 周期度伐利尤单抗治疗，对比术前4 周期安慰剂 + 含铂化疗，术后 12 周期安慰剂治疗，之前结果显示主要终点两组pCR率分别为17.2%和4.3%，P=0.000036中位EFS分别HR=0.68，P=0.003902，本次远期分析显示，度伐利尤围手术期治疗模式可以减少复发，增加手术完成率。 RATIONALE-315研究：替雷利珠单抗围手术期处理OS结果获阳！ 4、RATIONALE-315研究：替雷利珠单抗围手术期处理OS结果获阳！ RATIONAL315研究是针对可切除II-IIIA期NSCLC患者术前进行3-4周期的替雷利珠单抗+含铂双联化疗，术后接受最多8个周期的替雷利珠单抗辅助治疗，对比仅化疗术前术后处理，中期分析结果显示EFS HR 0.56，此次OS结果显示 HR 0.65，具有统计学和临床意义，开拓了国内免疫围手术期治疗新纪元。 5、Keynote671研究：K药围手术期治疗NSCLC，4年疗效更新（结阴：结阳） Keynote671研究：K药围手术期治疗NSCLC，4年疗效更新（结阴：结阳） STAS（气腔内播散）在IA期肺癌的预后价值 6、STAS（气腔内播散）在IA期肺癌的预后价值   基于III期JCOG0802研究（IA NSCLC）分析显示，节段切除和肺叶切除具有相似的局部复发率，但是无论何种切除方式，具有气腔内播散（STAS）的患者局部复发率均较高，组织分级3级的STAS发生率更高。 NADIM研究，化免围手术期处理模式对手术的影响 7、NADIM研究，化免围手术期处理模式对手术的影响 NADIM研究是在局部晚期可切除IIIA-IIIB期NSCLC患者开展的术前化免（O药+PC）新辅助治疗3周期，术后免疫辅助治疗6个月，对比仅进行术前化疗新辅助，获得了pCR率和MPR率的显著提升，此次对该研究的手术相关结果进行了总结汇报，显示出了该治疗模式在提升手术疗效的同时，安全性未见影响。 早期肺癌：VATS PK 开放手术，孰更优？ 8、早期肺癌：VATS PK 开放手术，孰更优？ 基于3项随机独立研究数据分析显示，全胸腔镜肺叶切除术（VATS）相比开放手术降低了21%的死亡风险。讨论考虑一些非肿瘤因素入院频率有关。 9、NeoADAURA研究：MRD分析显示ctDNA可作为新辅助治疗的预后因素 奥希替尼单药或奥希替尼联合化疗均能增加MRD的清除率，术前MRD的清除情况与MPR相关。 SKYSCRAPER-05研究：TIGIT抑制剂tiragolumab联合T药±化疗围手术期治疗II-IIIB期NSCLC。 10、SKYSCRAPER-05研究：TIGIT抑制剂tiragolumab联合T药±化疗围手术期治疗II-IIIB期NSCLC。 96% R0切除，很多学者对cohortA组的疗效获益非常感兴趣。   局晚期   1、特瑞普利单抗+化疗术前诱导不可手术局晚期NSCLC，手术转化率高！ 对于不可手术切除的III期NSCLC，采用替雷利珠单抗联合白紫+铂类诱导治疗2-4周期，手术转化率76.9%，pCR率55%。 2. EA5181研究：I药同步放化+免疫巩固对比单纯免疫巩固，未见疗效提升？PACIFIC模式仍是标准。 EA5181研究：I药同步放化+免疫巩固对比单纯免疫巩固，未见疗效提升？ 3、局晚期SCLC：大分割放疗 PK 常规分割，未达到非劣效终点 局晚期SCLC：大分割放疗 PK 常规分割，未达到非劣效终点 4、III期NSCLC汇总性图片 包括：III期NSCLC的可切除性建议，III期不可切除性NSCLC的2年OS率逐年变化   02   小细胞肺癌 1、SEZ6：SCLC新晋明星靶点 目前SCLC发现了众多可用靶点，包括B7H3、DLL3、HER3、TROP2、SEZ6，SEZ6 在神经内分泌肿瘤中高表达，其代表药物ABBV-706在本次大会公布了亮眼的疗效结果，在复发难治的SCLC患者中，ORR为56.1%-59.0%，PFS 5.6~6.8个月，在SCLC目前一众ADC药物中疗效显著。目前与免疫联合在SCLC的一线2/3期研究SEZanne计划开展，值得期待。 2、IDeate-Lung01研究：B7H3 ADC药物I-Dxd治疗SCLC II期结果坚挺！ I-Dxd是一款靶向B7H3的ADC药物，本次公布的结果显示，12 mg/kg I-Dxd治疗经治SCLC，确认ORR为48.2%，中位PFS和OS分别为4.9、10.3个月，二线和三线治疗的ORR分别为56.3%、45.7%。优秀的结果支持III期IDeate-Lung02研究的开展，为SCLC的破局提供新利剑。 3.DeLLphi-303研究：tarlatamab联合EP冲击ES-SCLC一线OS达25.3个月。   CD3/DLL3 BITE类药物tarlamab继获批SCLC二线治疗后，本次携一线数据强势亮相，在初治广泛期SCLC中，进行4~6周期的tarlatamab联合EP化免治疗后，采用tarlatamab+阿替利珠单抗/度伐利尤单抗维持治疗，结果显示，中位OS达到25.3个月，中位PFS为5.3个月，ORR29%。基于此，III期DeLLphi-305研究正在开展中。 DeLLphi-303研究：tarlatamab联合EP冲击ES-SCLC一线OS达25.3个月。   CD3/DLL3 BITE类药物tarlamab继获批SCLC二线治疗后，本次携一线数据强势亮相，在初治广泛期SCLC中，进行4~6周期的tarlatamab联合EP化免治疗后，采用tarlatamab+阿替利珠单抗/度伐利尤单抗维持治疗，结果显示，中位OS达到25.3个月，中位PFS为5.3个月，ORR29%。基于此，III期DeLLphi-305研究正在开展中。 DLL3 ADC SHR4849治疗复发SCLC初步疗效优秀！ 4、DLL3 ADC SHR4849治疗复发SCLC初步疗效优秀！  自DLL3的BITE型药物Tarlatamab获批小细胞肺癌后，该靶点被广泛开发，此次大会DLL3的ADC药物SHR4849（topo-I毒素）公布了I期临床疗效，整体有效率73.2%，DCR率93.0%；二线ORR为77%，DCR为97%；脑转移受试者ORR为83.3%，疗效喜人。 重新审视SCLC的分型和靶点 5、PDL1/VEGF-A双抗BNT327联合化疗一线治疗ES-SCLC，uORR 86.8%。 6、II研究：特瑞普利单抗用于同步放化疗后未进展的局晚期SCLC的巩固治疗 ADRIATIC研究（度伐利尤单抗）开创了免疫治疗作为局晚期SCLC同步放化疗后的巩固治疗模式，此次特瑞普利单抗也开展了相似的临床研究，结果显示，相比未进行巩固治疗，PFS和OS均有显著提升趋势（HR 0.54；0.41），相比ADRIATIC研究获益相近，再次印证了该治疗模式的地位。 7、卡瑞利珠单抗探索局晚同步放化疗夹心治疗模式初显疗效 度伐利尤单抗的ADRIATIC研究打开了免疫治疗在局晚期SCLC的临床应用，在此基础上，一些新的探索模式不断诞生，此次国内的卡瑞利珠单抗在局晚期SCLC，先进行化免2周期诱导+同步放化疗+免疫巩固，对比化疗诱导+同步放化疗，PFS和OS均有提升（HR=0.42；0.32），提出了更多可能。 8、广泛期SCLC的免疫治疗对比 9、局晚期SCLC目前正在开展的关键III期临床研究 涉及免疫、BITE、双抗，模式上多围绕同步放化疗开展的各类同步加持或巩固治疗模式。   03   间皮瘤 间皮瘤的治疗，依托病理来源不同推荐方案不一。靶点探索正在加快。 近期活动 9月26-29日，BiG将召开以「创新出海 云起潮升」为主题的第十一届IMPACT年会，届时上海杭州双城联动，向全球化，再出发！ ▼ 时间及地点： 9月26-27日 上海-张江希尔顿；规模：600-800人  9月29日 杭州-西湖大学；规模：100人（需单独注册） 报名入口 9月26-27日 上海会议注册码 9月29日 西湖大学会议注册码 会议门票：审核制(免费)，不含餐。优先Biotech/Pharma、临床、院校科学家、投资机构 付费门票：详见上二维码，注册内信息 1v1资本对接会  路演项目征集 可扫码填写项目信息 现场开放1v1咨询台，与各大头部VC面对面 ▼ 电脑端链接：https://event.mymova.com/spa4/#/?eventname=11bigvc 共建Biomedical创新生态圈！ 如何加入BiG会员？