编者按：2026年欧洲肺癌大会（ELCC）于3月25日至28日在丹麦哥本哈根盛大召开。作为全球肺癌领域最具影响力的学术盛会之一，本届大会在罕见靶点诊疗领域释放了诸多重磅信号：从HER2突变一线治疗格局的重塑，到KRAS G12D抑制剂的崭露头角，再到抗体药物偶联物（ADC）向一线治疗的战略前移，罕见靶点正从“边缘”走向“中心”。

 

会议期间，《肿瘤瞭望》特邀2026 ELCC大会科学委员会主席、英国皇家马斯登医院Sanjay Popat教授与国际肺癌研究协会（IASLC）主席、同济大学附属东方医院周彩存教授，立足大会最新进展，围绕“肺癌罕见靶点精准诊疗”热点话题进行深度探讨，以期为临床实践提供前沿洞见。

 

Sanjay Popat教授：罕见驱动基因突变非小细胞肺癌（NSCLC）的诊疗始终是我们面临的重大挑战，而精准的基因分型是识别这些患者的关键所在。近年来，个体化治疗取得了显著进展。在2026年ELCC大会上，我们看到了一系列极具影响力的数据更新，尤其是在HER2领域。Beamion LUNG-1研究的最新数据为Zongertinib在HER2酪氨酸激酶结构域（TKD）突变的晚期NSCLC中的美国食品药品监督管理局（FDA）获批提供了有力支持。该药物在初治患者中展现出快速且深度的缓解，确认客观缓解率（ORR）达76%，中位无进展生存期（PFS）为14.4个月，中位缓解持续时间（DoR）为15.2个月，均显示出持久的疗效。更为重要的是，我们首次观察到该药物在活动性脑转移患者中的颅内活性。研究显示，在伴有活动性脑转移的患者中，颅内ORR达47%，中位颅内PFS为8.2个月；而在未接受过脑部放疗的患者中，颅内ORR更是高达59%[1]。这一数据意义重大，因为此类患者群体通常被排除在临床试验之外。基于如此确切的全身及颅内疗效，我认为，在药物可及的前提下，Zongertinib应成为HER2突变晚期NSCLC一线治疗的标准。

 

Prof.Sanjay Popat：The rare driver diagnoses within non-small cell lung cancer are an ongoing problem，and it’s very important that we try and identify these patients accurately with appropriate genotyping.We continue to make huge advances in personalized therapy over the years.At ELCC 2026，we saw updates on these and for me，the most impactful data sets were for HER2.We had updated data which supports the FDA approval for Zongertinib for tyrosine kinase domain(TKD)mutant，advanced non-small cell lung cancer，here demonstrating very rapid responses，very deep responses，PFS in excess of 1 year.And for the first time，we’ve seen intracranial activity of the drug in patients with untreated，asymptomatic brain metastases，demonstrating very good response rates.And I think really，this is a standard first-line drug if available.I understand it’s available in China.I’m not sure about the regulatory environment，but from my viewpoint，the efficacy data is suitable for first-line treatment.

 

周彩存教授：确实如此。对于携带罕见驱动基因的患者，我们目前已有多种靶向药物可供选择。这些酪氨酸激酶抑制剂（TKI）不仅肿瘤缓解率高、无进展生存期长，且具备良好的中枢神经系统活性。我非常赞同Sanjay Popat教授的观点，TKI应成为HER2突变NSCLC一线治疗的标准。但当前的关键在于如何精准筛选出合适的患者。在中国，我们高度重视活检，通过超声支气管镜（EBUS）或穿刺获取足量组织进行检测。以往我们较多采用PCR检测，虽速度快但覆盖有限；如今我们更应推行大panel检测，这一点至关重要。

 

Prof.Caicun Zhou：That’s great.For patients with uncommon oncogenic drivers，nowadays we have targeted therapies for several of them.We have TKIs that are very good，with high tumor response rates and longer PFS.They also have CNS activity.I could totally agree with you:the TKI should be standard of care for first-line treatment of HER2 mutation，but nowadays we need to find the right patients with uncommon mutations.So in China we do a lot of biopsies.We try to get tissue.For us，we can do EBUS，we can do core needle biopsy，try to get enough tissue.Next，we need the test.Usually we perform a lot of PCR-based tests.PCR is faster，but we cannot do a panel.So nowadays we should do panel testing.

 

Sanjay Popat教授：完全正确。尤其是在EGFR 20外显子插入突变（EGFR ex20ins）领域，目前已发现数百种不同的插入变异，基于PCR的技术只能捕获极少部分。如果不采用二代测序（NGS），可能根本无法发现这类患者。

 

Prof.Sanjay Popat：It’s very true.And I think especially when it comes to something like EGFR exon 20 insertion，right?For example，we know in EGFR we have many hundreds of EGFR exon 20 insertion variants，and the PCR-based technologies will only pick up a very small number of these insertions.So if you’re not using NGS，you’re not going to find your patient.

 

周彩存教授：检测的重要性贯穿诊疗全程，不仅在基线，在疾病进展时同样需要再次检测。

 

Prof.Caicun Zhou：The testing is very important.Not only at the baseline，we also need to test at the time of disease progression.I think that’s correct.

 

Sanjay Popat教授：我们在临床中观察到患者可能出现脱靶驱动基因。例如，若考虑继续使用EGFR或ALK抑制剂，但在进展时发现了脱靶驱动基因，则继续使用TKI已无意义，患者需转向化疗或抗体药物偶联物（ADC）为基础的策略。因此，了解患者在初诊和复发时的生物学背景，对临床决策至关重要。

 

Prof.Sanjay Popat：One of the things we’re noticing is that patients have off-target drivers.So for example，if we’re thinking about giving another EGFR inhibitor or another ALK inhibitor，it’s pointless if there’s an off-target driver;those patients need a chemo-based strategy or ADC-based strategy to try and improve their outcomes.So understanding the biology of the patient at diagnosis and at relapse is，I think，critical to the decision making.

 

周彩存教授：除了HER2突变，KRAS G12D领域也有令人兴奋的进展。一些化合物显示出约40%的缓解率和较长的PFS，但截至目前，我们尚无这些药物在中枢神经系统中是否有效的数据。在中国和美国均是如此。

 

Prof.Caicun Zhou：Right.So except for HER2-mutant lung cancer，we also have very interesting compounds for KRAS G12D.There are some compounds showing benefit，with around 40%response rates and quite longer PFS for survival.So far，we do not have any data on whether these compounds work or not in the CNS.In China and the United States，that’s right.

 

Sanjay Popat教授：KRAS G12D领域确实非常令人期待。在亚洲，KRAS G12D突变NSCLC的发生率远高于西方，而西方以KRAS G12C突变更为常见。这是一个非常重要的领域，不仅关乎胰腺癌，也关系到从不吸烟者和吸烟者中的KRAS G12D突变肺癌患者。该领域正快速发展，涌现出多种不同的药物。

 

Prof.Sanjay Popat：The KRAS G12D space，I think，is a very exciting space.In Asia，you see a lot more G12D non-small cell lung cancer than we do in the West，where G12C is more common.But this is a very important area.It’s a big problem for pancreatic cancer，but also for never-smoker and smoker populations with G12D KRAS-mutant lung cancer.And this area，I think，is evolving very，very quickly with many different agents.

 

周彩存教授：我们特别关注联合治疗，尤其是与免疫治疗的联合。但毒性问题，特别是肝毒性，不容忽视。部分患者无法耐受KRAS G12C抑制剂联合免疫治疗。

 

Prof.Caicun Zhou：Especially we talk a lot about combination therapy.We talk about combining with IO，but toxicity is a kind of problem，especially liver toxicity.Some patients could not tolerate the combination of a KRAS G12C inhibitor plus IO.

 

Sanjay Popat教授：我完全同意。KRAS G12C抑制剂活性很强，但要推向一线，必须与免疫检查点抑制剂联合，有时甚至需要联合化疗。我们观察到高发的腹泻、转氨酶升高，部分源于免疫激活，部分来自药物本身。这些患者常需使用激素，如何确保他们安全完成全程治疗是一大挑战。随着KRAS G12D抑制剂的开发，我们同样需要关注其不良反应谱。

 

Prof.Sanjay Popat：I think this is completely correct.KRAS G12C inhibitors are very active，but we need to combine them with checkpoint inhibitors to move to first line.And sometimes perhaps even with chemo as well.We see very high rates of diarrhea，we see high rates of ALT/AST rise.Sometimes it’s due to immune activation，sometimes it’s due to the drug itself.These patients often need steroids.It can become very problematic to make sure they get the right treatment all the way through.We’re starting to see signals of that with some types of G12D inhibitors as well.And we have to be mindful of the adverse event profile as these drugs continue to be developed.

 

周彩存教授：因此，我们需要研发更有效的KRAS G12C和HER2抑制剂。要开发更有效的KRAS抑制剂，可以利用新技术，如蛋白降解剂。

 

Prof.Caicun Zhou：So another way is we should produce more potent KRAS G12C and HER2 inhibitors.To produce more potent KRAS inhibitors，we can use new technology such as protein degraders.

 

Sanjay Popat教授：没错。KRAS药物开发有多种途径，我们需要思考是水平抑制、垂直抑制，还是使用分子胶或其他形式的蛋白降解剂。许多不同的靶点正在被开发。我认为未来几年KRAS领域的研发将非常精彩。在KRAS G12C已确立、新一代药物和KRAS G12D抑制剂即将涌现的同时，泛RAS抑制剂也初现端倪。问题在于，我们应选择突变特异性抑制剂、泛RAS抑制剂，还是需要联合治疗？

 

Prof.Sanjay Popat：That’s right.And I think there are many different approaches to drugging KRAS.We need to think about whether we drug it horizontally，vertically，whether we use a molecular glue or some other form of protein degrader.Many different targets are being developed.There are many different approaches to this.I think the next few years in the development space of KRAS，in general，is going to be very，very interesting.Because in the space that we have already established with G12C，we have next-generation G12C coming.We have first-generation G12D nearly around the corner，but we also have pan-RAS inhibitors as well.The question is，how do we then work out which is the right strategy to use?Do we use a mutation-specific inhibitor，pan-RAS，or do we even need combinations?

周彩存教授：这正是关键问题，我完全同意。但我们将目光投向ADC时代。现在我们有了ADC联合化疗、ADC联合免疫治疗、ADC联合双特异性抗体。如果ADC联合免疫治疗比KRAS G12C抑制剂联合免疫治疗疗效更好，我们还需要开发更有效的TKI吗？TKI毒性更小，更易于给药。

 

Prof.Caicun Zhou：I totally agree with you.But we look forward to the ADC era.Now we have ADC plus chemo，ADC plus IO，ADC plus bispecifics.If ADC plus IO produces better efficacy compared with KRAS G12C inhibitor plus IO，do we still need to develop more potent TKI?TKI is less toxic and easier to administer.

 

Sanjay Popat教授：我认为这非常正确。ADC领域发展迅速，尤其在中国。我对中国正在开发的众多ADC非常感兴趣，你们在临床试验招募和展示这些药物的疗效与安全性方面做得非常出色。但有趣的是，在某些情况下，这些ADC可能会进入一线治疗，无论是单药还是联合免疫检查点抑制剂。现在关键问题是，如果这些药物进入一线，那么靶向治疗的位置在哪里？特别是对于KRAS？我认为对于EGFR突变肺癌，我们仍然需要某种TKI作为基础。但我可以看到未来EGFR领域一线TKI联合ADC的局面。在这种情况下，罕见突变亚型该如何应对？在罕见领域生成数据将非常困难。但这就是我们前进的方向，或许在EGFR领域，这将对更广泛的驱动基因阳性领域产生深远影响。

 

Prof.Sanjay Popat：I think this is very true.The field of ADCs is moving very，very quickly，especially in China.I’m very interested in the number of ADC compounds which are being developed in China，and you are doing a great job，I have to say，in recruiting to trials and demonstrating the efficacy and safety profile of these.But what is becoming very interesting is，in some scenarios，these ADCs，I think，may move to first line，either as monotherapy or probably in combination with a checkpoint inhibitor.Now，the key issue is，if these are moving to frontline，then where do the targeted therapies fit in?Particularly when it comes to KRAS?I think for EGFR-mutant lung cancer，we’re still going to need to have some sort of TKI;that’s still going to be the backbone.But I can see a world where it’s going to be first-line TKI plus ADC in the future for EGFR.What do we do about rarer mutation subtypes in that scenario?It’s going to be very hard to generate data in that rare space.But this is the way we’re moving，perhaps in EGFR，and that has broader implications for the wider oncogene-addicted field.

 

周彩存教授：我完全同意。在中国，我们有多个III期试验在比较EGFR抑制剂联合，尤其是第三代EGFR-TKI联合ADC。我们将在不久的将来获得数据。如果PFS能够进一步改善，这种联合治疗将成为新的标准治疗。

 

Prof.Caicun Zhou：I totally agree with you.In China，we have several phase III trials comparing EGFR inhibitor plus，especially the third-generation EGFR TKI plus ADC.We have so many such kinds of trials.We will know the data in the near future.If the PFS could be further improved，that combination will become the new standard of care.

 

Sanjay Popat教授：我认为是的。我们需要确定的关键问题之一是，在一线应该使用哪种类型的ADC？我们有许多正在开发的TROP2 ADC，它们的疗效特征略有不同，毒性特征也截然不同。我们如何选择正确的ADC与TKI联合？这是一个持续的挑战。

 

Prof.Sanjay Popat：I think so.One of the key issues we need to establish is what is the right type of ADC to be using upfront?We have many TROP2 ADCs in development.They all have a slightly different efficacy profile.They definitely have a different toxicity profile.How do we then choose the right ADC to partner with whichever TKI?This is an ongoing challenge.

 

周彩存教授：我认为是的。尤其在中国，我们有多种ADC。我们有EGFR ADC，有双特异性ADC（EGFR-MET ADC），也有许多HER2 ADC。

 

Prof.Caicun Zhou：Especially in China，we have so many kinds of ADCs.We have EGFR ADC，we have bispecific ADC(EGFR-cMET ADC)，EGFR-HER3 ADC，we also have so many HER2 ADCs.

 

Sanjay Popat教授：我认为一个仍然非常相关的问题是，到底是有效载荷（payload）更重要，还是靶点更重要？

 

Prof.Sanjay Popat：One of the questions I think is still really relevant is，is it really the payload that’s more important，or is it the target that’s more important?

 

周彩存教授：我认为，对于ADC来说，如果靶点没有差异，那么有效载荷就成为关键。所以在中国，我们正在开发混合有效载荷的ADC。我们可以在一个ADC中放入两种有效载荷。我们也有混合靶点ADC，如TROP2联合另一个靶点。这种双靶点ADC的研究正在进行中，目前尚无数据。这是一个非常有趣的问题。

 

Prof.Caicun Zhou：I would say，for an ADC，if there is no difference in the target，then the payload becomes the key.So in China，we are developing mixed payload ADCs.We can do two payloads in one ADC.We also have mixed ADCs such as TROP2 plus another target.This kind of dual-target ADC study is just ongoing.So far，we do not have any data.That’s a very kind of problem.

 

Sanjay Popat教授：我非常期待这方面的进展，因为我认为双有效载荷和生物有效载荷非常有趣，可能会占据主导地位。但ADC有许多不同的优化需求需要解决：我们是否获得了足够的靶点覆盖？我们是否具有足够的细胞毒性？最重要的是，我们是否获得了足够的脑穿透性？因为我们不能忘记，在肺癌领域，我们积累到的经验是：脑部控制等于最佳生存。

 

Prof.Sanjay Popat：I’m very much looking forward to this，because I think dual payloads and biological payloads are very interesting，and may take over.But there are so many different optimization needs for ADCs that we have to work out.Are we getting enough target coverage?Are we really having enough cytotoxicity?And above all，are we getting adequate brain penetration?Because we can’t forget that at the end of the day，one lesson we’ve learned，I think，in lung cancer is brain control equals best survival.

 

周彩存教授：尤其当患者生存期延长时，脑转移成为我们需要解决的更重要的问题。所以现在我们正试图开发具有中枢神经系统穿透性、中枢神经系统活性的化合物与ADC联合。我认为这是一种控制中枢神经系统转移的双重化合物策略。相关研究正在进行中，目前尚无数据可分享。

 

Prof.Caicun Zhou：Especially if patients survive longer，brain metastasis becomes a more important question we need to answer.So nowadays we try to develop CNS-penetrative，CNS-active compounds combined with ADC.So I would say that is a dual compound approach to control CNS metastasis.So the study is ongoing;so far，do not have any data to tell you.

 

Sanjay Popat教授：我认为我们可以达成共识，未来几年药物开发领域将非常令人兴奋。我们有许多正在开发的药物，包括靶向药物（TKI）、多种RAS抑制剂，还有许多免疫治疗双特异性化合物正在开发。新型免疫检查点正在建立。在此背景下，我们有新型ADC，包括传统ADC、新型有效载荷ADC和双特异性ADC。我们如何将这些组合起来，真正为患者最大化获益？这将是一个巨大的挑战。

 

Prof.Sanjay Popat：I think we can agree that the next few years are going to be very exciting in the world of drug development.We have many drugs being developed，both targeted agents(TKIs)，both RAS inhibitors in many different aspects，and we have many IO bispecific compounds being developed.We have novel types of IO checkpoints being established.And on the background of that，we have novel ADCs，both traditional ADCs and novel payloads，and bispecific ADCs.How do we combine all of these to really maximize the outcomes for our patients?This is going to be a big challenge.

 

周彩存教授：这是一个非常重要的问题。如果ADC联合免疫治疗成为标准治疗，门槛会更高。下一个ADC很难再与之联合。我不确定下一个ADC能否超越这一标准。

 

Prof.Caicun Zhou：A very important question we need to answer.If ADC plus IO becomes standard of care，the bar becomes higher.It’s difficult for the next ADC to combine with it.I’m not sure the next ADC could beat that standard.

 

Sanjay Popat教授：这确实是个问题。也许在未来几年内，我们会在疗效上达到某种平台期。我认为这将是一个“幸福的烦恼”。所以让我们继续推进临床试验，确保患者能够接触到新治疗，最重要的是，确保我们拥有精准、准确的基因分型。没有准确的基因分型，我们就无法恰当地对患者进行分层，为他们提供正确的治疗。

 

Prof.Sanjay Popat：Maybe we are in a position where over the next few years we reach a sort of plateau in activity.I think this would be a nice problem to have.So let’s carry on recruiting to trials，making sure that our patients get exposure to new treatments，and above all，ensure we have very good and accurate genotyping.Without accurate genotyping，we cannot properly stratify our patients to get them the right treatment.

 

周彩存教授：我完全同意。生物标志物始终重要。我们需要生物标志物，我们需要组织，我们需要检测。但到目前为止，我们还没有非常好的ADC生物标志物，尤其是对于TROP2 ADC。TROP2 ADC在我们的市场上可用于EGFR突变肺癌。我认为TROP2 ADC将可用于治疗野生型晚期NSCLC。

 

Prof.Caicun Zhou：I totally agree.Biomarkers are always important.We need biomarkers，we need tissue，we need to test.But so far，we do not have any very good biomarker for ADCs，especially for TROP2 ADC.TROP2 ADC is available in our market for EGFR-mutant lung cancer.I would say the TROP2 ADC will be available in the market to treat wild-type advanced non-small cell lung cancer.That’s true.

 

Sanjay Popat教授：确实如此。一些ADC正在开发预测性免疫组化评分，利用数字病理平台评估TROP2或HER2表达。另一些ADC则在开发中不要求靶点表达。我们需要观察实施的障碍是什么、生物标志物检测的疗效获益是什么、安全性平衡如何。但随着这些药物不断进化和发展，我认为未来几年将非常有趣。我们密切关注这一领域。毫无疑问，TROP2对于EGFR突变人群和野生型人群都是一个非常可行的靶点。关键问题是，对于野生型人群，我们是否需要生物标志物分层？这是一个持续的关键问题。

 

Prof.Sanjay Popat：That’s true.And some ADCs are being developed with a predictive immunohistochemistry(IHC)score，looking at TROP2 or HER2 expression using digital pathology platforms.Other ADCs are being developed without a requirement for target expression.We have to see what the barriers to implementation are，what the efficacy benefits are for biomarker testing，and what the safety balances are.But I think it’s going to be very interesting over the next few years as these drugs continue to evolve and develop.We keep a very careful eye on this space.Certainly，TROP2 is a very，very viable target for the EGFR-mutant population and a very viable target for the wild-type population.The key issue is，do we need biomarker stratification for the wild-type population or not?This is a key ongoing question.

 

周彩存教授：所以我们需要共同努力解决这个问题，为未来的精准医学找到正确的生物标志物。

 

Prof.Caicun Zhou：So we need to work together to solve the problem，to find the right biomarker for future precision medicine.

 

Sanjay Popat教授：我完全同意。

 

Prof.Sanjay Popat：I would totally agree.