A Phase I Pilot Study to Evaluate the Bioequivalence, Pharmacokinetics, and Safety of Inhaled Afatinib Dimaleate Compared to the Reference Oral Afatinib Dimaleate in Healthy Smoking Volunteers (EDDIS-a1)

This is a pilot Phase I open-label randomized single-dose two-period crossover study (in the EDDIS project) evaluating the bioequivalence, pharmacokinetics (PK), safety, and tolerability of inhaled afatinib dimaleate compared with the reference oral afatinib dimaleate in healthy volunteer smokers.
The study will enroll healthy adult volunteers smoker to assess the systemic exposure and lung deposition of inhaled afatinib dimaleate. Participants will receive both the test inhaled formulation and the reference oral formulation in separate periods with delayed phase between treatments.
Key endpoints include maximum plasma concentration (Cmax), area under the concentration-time curve (AUC), and lung deposition assessed via bronchoalveolar lavage (BAL), frequency of occurrence of side effects and cases of toxicity during the studies

开始日期2025-04-19

申办/合作机构-

NCT06753747

/ Not yet recruiting临床1/2期IIT

A Phase 1b/2 Trial of Afatinib Plus Palbociclib in Previously Treated Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

The goal of this clinical trial is to learn if Afatinib plus Palbociclib works in previously treated recurrent or metastatic esophageal squamous cell carcinoma. It will also learn about the safety of the combination of Afatinib and Palbociclib. The main questions it aims to answer are:
What is the safe and tolerable dose of Afatinib when combined with 100 mg of Palbociclib (administered orally, three weeks on and one week off)?
Does the combination therapy of Afatinib and Palbociclib induce a tumor response in patients with recurrent or metastatic esophageal squamous cell carcinoma who have received prior treatments?

开始日期2025-04-01

申办/合作机构

四川大学华西医院（四川省国际医院）

CTRI/2025/03/082447

/ Not yet recruitingN/AIIT

A comparative efficacy and safety of Oral Afatinib Targeted therapy plus chemotherapy versus Chemotherapy alone in locally advanced squamous cell cancer of Head and neck region from Tertiary care hospital in central India: A Randomized controlled trial - NIL

开始日期2025-03-30

申办/合作机构-

100 项与马来酸阿法替尼相关的临床结果

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100 项与马来酸阿法替尼相关的转化医学

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100 项与马来酸阿法替尼相关的专利（医药）

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3,808

项与马来酸阿法替尼相关的文献（医药）

2025-12-01·CANCER CHEMOTHERAPY AND PHARMACOLOGY

Evolution of computational techniques against various KRAS mutants in search for therapeutic drugs: a review article

Review

作者: Subramaniyan, Vetriselvan ; Ogaly, Hanan A ; Mehmood, Ayesha ; Khalid, Asaad ; Wadood, Abdul ; Hakami, Mohammed Ageeli

KRAS was (Kirsten rat sarcoma viral oncogene homolog) revealed as an important target in current therapeutic cancer research because alteration of RAS (rat sarcoma viral oncogene homolog) protein has a critical role in malignant modification, tumor angiogenesis, and metastasis. For cancer treatment, designing competitive inhibitors for this attractive target was difficult. Nevertheless, computational investigations of the protein's dynamic behavior displayed the existence of temporary pockets that could be used to design allosteric inhibitors. The last decade witnessed intensive efforts to discover KRAS inhibitors. In 2021, the first KRAS G12C covalent inhibitor, AMG 510, received FDA (Food and drug administration) approval as an anticancer medication that paved the path for future treatment strategies against this target. Computer-aided drug designing discovery has long been used in drug development research targeting different KRAS mutants. In this review, the major breakthroughs in computational methods adapted to discover novel compounds for different mutations have been discussed. Undoubtedly, virtual screening and molecular dynamic (MD) simulation and molecular docking are the most considered approach, producing hits that can be employed in subsequent refinements. After comprehensive analysis, Afatinib and Quercetin were computationally identified as hits in different publications. Several authors conducted covalent docking studies with acryl amide warheads groups containing inhibitors. Future studies are needed to demonstrate their true potential. In-depth studies focusing on various allosteric pockets demonstrate that the switch I/II pocket is a suitable site for drug designing. In addition, machine learning and deep learning based approaches provide new insights for developing anti-KRAS drugs. We believe that this review provides extensive information to researchers globally and encourages further development in this particular area of research.

2025-10-01·IMMUNOLOGY LETTERS

Impact of afatinib on intestinal and salivary IgA: Immune response alterations linked to gastrointestinal side effects

Article

作者: Uemura, Ippei ; Takahashi-Suzuki, Natsuko ; Satoh, Takashi

BACKGROUND:

Afatinib, an oral molecular-targeted anticancer agent, is effective but causes significant gastrointestinal side effects. These effects are associated with EGFR inhibition in intestinal cells and changes in the microbiota.

OBJECTIVE:

To investigate the effects of afatinib on intestinal mucosal immunity in rats, focusing on IgA levels in the intestine and saliva, and to understand the innate and acquired immune responses to these side effects.

METHODS:

Male Wistar rats received afatinib (5.2 mg/kg) daily for 24 h (Day 1) and for 2 weeks (Day 14). Gene expression in the intestine was analyzed using quantitative polymerase chain reaction. IgA levels in the intestine and saliva were measured using enzyme-linked immunosorbent assay.

RESULTS:

Afatinib suppressed α-defensin 5 and pIgR in the jejunum and ileum, indicating reduced innate immunity. It increased IgA levels in the intestine and saliva, suggesting altered acquired immunity. Salivary IgA levels significantly correlated with intestinal IgA levels.

CONCLUSIONS:

Afatinib affects gastrointestinal mucosal immunity, suppresses innate defense, and alters IgA production. Salivary IgA could serve as a marker for monitoring these effects, aiding cancer therapy management.

2025-08-01·JOURNAL OF CLINICAL EPIDEMIOLOGY

The importance of reporting computed tomography scan intervals in real-world oncology studies: a simulation analysis of afatinib in advanced-stage non-small cell lung cancer

Article

作者: Geater, Sarayut Lucien ; Iwsakul, Sasiwimon

OBJECTIVES:

In real-world oncology studies, progression-free survival (PFS) is often used as a surrogate endpoint. However, the interval of the computed tomography (CT) scans, which might impact PFS, is usually not mentioned in publications based on real-world data. This study aims to determine the relationship between CT scan interval and PFS captured across different assessment frequencies (captured PFS or cPFS). The secondary objective is to identify appropriate correction factors for median PFS (mPFS) in real-world data, necessary for comparisons with clinical trials.

STUDY DESIGN AND SETTING:

A simulation was conducted to create theoretical PFS data. Time-to-event analyses, including Kaplan-Meier survival curves, Cox regression models, parametric survival models, and multilevel survival regression models, were used to assess the effect of various CT scan intervals on cPFS durations. The Laplace regression model was used to compute fiftieth-percentile ratios.

RESULTS:

The mPFS (95% CI) captured by cPFS6, cPFS12, cPFS16, and cPFS20 were 11.56 (10.78, 12.71), 12.42 (11.17, 13.80), 12.98 (11.70, 13.96), and 13.80 (12.71, 14.49) months, respectively. There was a significant difference in mPFS durations captured at different CT scan intervals. The correction factors for converting mPFS from cPFS12, cPFS16, and cPFS20 to cPFS6 were 1.06, 1.09, and 1.14, respectively.

CONCLUSION:

Longer CT intervals resulted in longer mPFS, leading to a systematic overestimation of about 1 to 2 months.

235

项与马来酸阿法替尼相关的新闻（医药）

2025-06-23

·CPHI制药在线

老靶点EGFR在肺癌领域的创新韧性

关注并星标CPHI制药在线近日，翰森制药宣布，其第三代EGFR-TKI阿美替尼（Aumseqa）的上市许可申请，已获英国药品和健康产品管理局 (MHRA）批准，作为单药治疗成人局部晚期或转移性非小细胞肺癌（NSCLC）且具有激活的EGFR突变的患者的一线治疗，以及成人局部晚期或转移性EGFR T790M突变阳性NSCLC患者的治疗，成为首个出海欧洲的中国原研三代EGFR-TKI。从NDA受理到获批，阿美替尼历经了三年的漫长等待。阿美替尼的成功出海，再次彰显了EGFR这一老靶点的创新韧性。EGFR的作用机制EGFR（表皮生长因子受体）是一个跨膜酪氨酸激酶受体，对于细胞增殖、迁移、分化等都发挥着关键作用。当EGFR与表皮生长因子（EGF）结合后，可参与细胞正常生长和分裂，是人体表皮细胞的调控开关。TKI（酪氨酸激酶抑制剂）是一组通过多种抑制模式破坏蛋白激酶信号转导通路的药物。EGFR-TKI可通过竞争性抑制EGFR的ATP结合位点，阻断EGFR的自磷酸化和下游信号通路的激活，实现抑制肿瘤细胞的增殖、存活和诱导肿瘤细胞凋亡的治疗目的。EGFR基因在非小细胞肺癌（NSCLC）中的总体发生率为17.2%。但在包括中国在内的东南亚地区，其发生率则高达40%-60%。因此，EGFR-TKI成为NSCLC领域的主流治疗药物。从EGFR发现至今，EGFR-TKI已历经三代更迭。如今，第四代已箭在弦上，另外还有其他技术路线产品正在临床阶段。EGFR-TKI的造富能力有多强？2002年，阿斯利康的吉非替尼（Gefitinib）在日本获批上市，开启了EGFR-TKI时代。目前，已经历三代更迭，代表产品分别是：第一代：吉非替尼、厄洛替尼、埃克替尼；第二代：阿法替尼、达可替尼；第三代：奥希替尼、阿美替尼、伏美替尼、贝福替尼、奥莫替尼、兰泽替尼、瑞齐替尼。吉非替尼上市首年销售额便达到6700万美元，2003年获FDA批准上市，销售额暴涨240%，高达2.28亿美元。罗氏的厄洛替尼于2004年获得FDA批准后，销售额也一路高涨，2013年达到销售额巅峰13.39亿法郎（14.58亿美元）。2015年11月，阿斯利康的奥希替尼（Tagrisso）获FDA批准上市，用于单药一线治疗外显子19缺失（EGFR ex19del）或外显子21 L858R突变（EGFR ex21 L858R）的局部晚期或转移性非小细胞肺癌（NSCLC）患者，开启了三代EGFR-TKI治疗时代。目前，该药物已获批5项适应症。奥希替尼自上市以来销售额稳步上升，2018年被批准一线疗法后销售额突飞猛进，2021年首次突破50亿美元大关，2023年全球销售额达到57.99亿美元，2024年全球销售额达到65.80亿美元，成为阿斯利康第二大畅销药。成立于2003年的贝达药业，更是凭借中国第一个自主研发的EGFR-TKI-盐酸埃克替尼（商品名：凯美纳），成为国内首个销售额破十亿的创新药。目前成为主流的三代EGFR-TKI依然面临着严峻的肿瘤耐药挑战，在经奥希替尼二线治疗后出现耐药的NSCLC患者中，大约10%-26%的患者存在EGFR C797S耐药性突变。EGFR-TKI与肺癌的对抗之战已然来到第四阶段。"后EGFR时代"之战目前第四代EGFR-TKI大战已经打响，全球约有20多款四代EGFR-TKI进入临床，其中以Black Diamond Therapeutics的BDTX-1535的数据最为亮眼。BDTX-1535是一种中枢神经系统渗透剂第四代不可逆（共价）EGFR抑制剂，可靶向第三代EGFR TKI获得性和内在耐药性突变，对野生型EGFR有选择性，同时有很好的渗脑作用。在II期研究中，接受每日1次200mg BDTX-1535治疗的EGFR突变型NSCLC患者有42%（8/19）实现了客观缓解（ORR）。为了克服EGFR-TKI耐药难题，行业还开发了EGFR抗体、EGFR ADC、EGFR PROTAC等方向产品。EGFR抗体的研发很早就开始了，但在肺癌治疗领域一直未能成功，这是因为EGFR信号通路的激活依赖于配体介导的EGFR受体二聚化，EGFR单抗可以与EGFR胞外区结合，抑制配体介导的受体二聚化，从而抑制EGFR信号传递。而EGFR突变发生在胞内区，因此EGFR单抗无法阻止EGFR信号传递。2015年，首款EGFR单抗necitumumab获批用于治疗NSCLC，不过疗效非常有限。2021年5月，强生的EGFR/cMET双抗埃万妥单抗以I期试验结果获得FDA加速批准，用于治疗铂化疗后进展的EGFR 20ins突变的局部晚期或转移性NSCLC，成为首个成功进入肺癌领域的EGFR抗体疗法。在EGFR单抗的基础上，ADC技术带来了新的突破。乐普生物的EGFR ADC新药维贝柯妥塔单抗（MRG003）是国内进展最快的，由EGFR靶向单抗与强效的微管抑制剂MMAE分子通过vc链接体偶联而成，维贝柯妥塔单抗针对肺癌的适应症正在临床研究中。PROTAC作为一种具有新结构新机制的肿瘤靶向药物，可以降解整个蛋白而不仅仅是抑制酶活性，因此可能克服耐药性问题，是EGFR赛道一个理想的成药方向。全球已有20多个PROTAC药物进入临床研究，包括海思科的EGFR PROTAC药物HSK40118和贝达药业/C4 Therapeutics的EGFR PROTAC药物CFT8919，正在开展临床试验，用于治疗不可手术的、携带EGFR突变的晚期NSCLC患者。历久弥新的EGFR靶点，在一代代技术更迭下，演绎着属于自己的创新韧性。参考来源： 1.翰森制药公告 2.Dawei Hong, Bizhong Zhou, Bei Zhang, Hao Ren, Liquan Zhu, Guowan Zheng, Minghua Ge, Jingyan Ge, Recent advances in the development of EGFR degraders: PROTACs and LYTACs, European Journal of Medicinal Chemistry Volume 239, 5 September 2022, 114533. 3.Specific non-genetic IAP-based protein erasers (SNIPERs) as a potential therapeutic strategy. Eur J Med Chem 2021;216:113247.END来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

上市批准申请上市医药出海

2025-06-17

·PRNewswire

Lung Cancer Research Foundation Announces Request for Proposals Focused on Curing EGFR Mutant Lung Cancers

New Team Science Award is $1.5 million Over Three Years NEW YORK, June 17, 2025 /PRNewswire/ -- The Lung Cancer Research Foundation (LCRF) announces today a new funding mechanism: the 2025 LCRF Team Science Award on Advancing Therapies Toward Curing EGFR Mutated Lung Cancers. The Request for Proposals is now open for submissions. Designed to bring together scientific teams to accomplish innovative breakthroughs, this team science award must include at least two projects directed at understanding and treatment of resistant or persistent disease in EGFR mutated lung cancer. Lung cancer is responsible for more deaths worldwide than any other cancer, accounting for an estimated 124,730 deaths annually in the United States alone.1 In the last 10 to 15 years, accelerated clinical trials and FDA approvals of targeted therapies for non-small cell lung carcinoma have been possible in part due to advances in molecular profiling of tumors. Many of these targeted therapies are directed against oncogenic drivers. Epidermal growth factor receptor (EGFR) mutations were the first oncogenic drivers that were successfully targeted with the use of tyrosine kinase inhibitors (TKIs). Subsequently additional oncogenic driver alterations in EML4-ALK, BRAF, RET, KRAS G12C, HER2, MET, NTRK, ROS1 and NRG1 were identified along with corresponding therapeutic options for treatment. Several TKIs including gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib have been approved by the FDA for the treatment of EGFR mutated (EGFRmut+) Non Small Cell Lung Cancer (NSCLC.) Despite substantial progress in the treatment of EGFRmut+ lung cancer, available treatments are not curative, and resistance invariably develops. Sometimes biopsies are repeated to identify the source of resistance to potentially evaluate patients for additional targeted therapy. Usually, at some point in time chemotherapy is employed to treat the disease. Immunotherapy in the form of PD-1/PD-L1 inhibitors has revolutionized the treatment of many forms of lung cancer but has not proven effective in the treatment of most oncogene-driven lung cancers. Given that therapeutic options available to date are not curative, there is a need for novel approaches to treat these lung cancers and improve outcomes for patients with the ultimate intention of cure. This grant mechanism will focus on furthering the development of novel therapies for patients with EGFRmut+ NSCLC. "There has been so much scientific discovery in EGFR mutated lung cancer, and with the development of targeted treatments, patients are living longer," said Benay Taub, lung cancer survivor. "However, even with the best of circumstances, resistance develops and we need patients to have more treatment options. The goal of this award is to support a team of committed researchers in pursuit of improved treatments and outcomes for lung cancer patients and hopefully, one day, a cure." "EGFR discoveries were the start of oncogene-driven treatment and while the science has made great strides, there is still a significant need for more to be discovered," says Dr. Antoinette Wozniak, Chief Scientific Officer for LCRF. "Our commitment to people affected by lung cancer is simple: continue to fund research that pushes the boundaries of what is known to what is possible – toward a cure. This award will hopefully move the science in that direction." "Tomorrow's breakthroughs are made possible by research that happens today," emphasized David Carbone, MD, PhD, Director, Translational Therapeutics Program, The Ohio State University Wexner Medical Center and member of LCRF's Scientific Advisory Board. "Taking a team approach to combatting resistance in EGFR mutant lung cancer promises to accelerate the pace of discovery." This new Team Science Award is made possible by a generous private donation from Benay and Steven Taub. Their visionary support reflects a deep belief in the power of collaboration to drive scientific discovery. Submissions to the Request for Proposals will be reviewed through a two-step process: Letters of Intent will be accepted until midnight on July 29, 2025; if selected, projects will then be chosen to submit full proposals. All applications will be subject to a rigorous review by LCRF's Scientific Advisory Board. More details about the Request for Proposal, along with eligibility, requirements, and deadlines can be found at LCRF.org/FundingOpportunities. Siegel RL, Giaquinto AM, Jemal A. CA: A Cancer Journal for Clinicians, Vol 24,Issue 1, Jan/Feb 2024 About the Lung Cancer Research Foundation (LCRF) The Lung Cancer Research Foundation® (LCRF) is the leading nonprofit organization focused on funding innovative, high-reward research with the potential to extend survival and improve quality of life for people with lung cancer. LCRF's mission is to improve lung cancer outcomes by funding research for the prevention, diagnosis, treatment, and cure of lung cancer. To date, LCRF has funded 429 research grants, totaling nearly $48 million, the highest amount provided by a nonprofit organization dedicated to funding lung cancer research. For more information about the LCRF grant program and funding opportunities, visit lcrf.org/research. Contact: LUNG CANCER RESEARCH FOUNDATION (LCRF) Sheila Sullivan Sr. Director, Marketing & Communications [email protected] SOURCE Lung Cancer Research Foundation WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

免疫疗法临床研究

2025-06-14

·医药速览

HER2和EGFR的20号外显子插入突变为何难出药？

在肺癌领域，HER2和EGFR基因的突变一直是研究的重点。HER2（人表皮生长因子受体2）和EGFR（表皮生长因子受体）是酪氨酸激酶受体家族的成员，它们在细胞生长、分化和存活中起着关键作用。当这些基因发生突变时，可能导致细胞的异常增殖，从而引发癌症。其中，HER2和EGFR基因的20号外显子插入突变是两种较为特殊且“难治”的突变类型，它们在肺癌患者中的比例相对较低，但治疗难度较大，目前缺乏理想的药物。HER2/EGFR 20号外显子插入突变的基本特性（一）突变位置与常见突变形式HER2 20号外显子插入突变：突变位于激酶结构域C端附近（20号外显子），常见突变形式包括YVMA、G778_P780dup等。这些插入突变会导致HER2蛋白的结构发生改变，从而影响其功能。EGFR 20号外显子插入突变：突变发生在激酶结构域（20号外显子），常见的插入突变形式有A763_Y764insFQEA、D770_N771insSVD等。这些突变同样会改变EGFR蛋白的三维结构，进而影响其与底物的结合和催化活性。（二）活性变化与结构特征活性变化：这两种突变均为激活型突变，即它们会导致HER2和EGFR蛋白的激酶活性增强，从而促进细胞的增殖和存活。这种异常的活性是肿瘤发生和发展的关键因素之一。结构特征：HER2 20号外显子插入突变使得激酶活性增强，同时空间位阻增大，这使得药物难以接近并结合到其活性位点。而EGFR 20号外显子插入突变则导致构象更加封闭，ATP结合口袋难以接近，这进一步增加了药物设计的难度。EGFR 20号外显子插入突变结构示意图为何很难设计出高效小分子药物？（一）突变位点靠近ATP结合口袋导致空间拥挤插入突变会“向外鼓出”额外的氨基酸残基，使得结合口袋的构象发生改变，空间变得狭窄，药物难以进入。传统的EGFR/HER2抑制剂，如阿法替尼、厄洛替尼等，在设计时并未考虑到这种结构变化，因此它们与插入突变型受体的结合效率大幅下降。这就像是原本设计好的钥匙无法匹配经过改造的锁孔一样，药物无法有效地与突变蛋白结合，从而无法发挥其抑制作用。（二）难以兼顾选择性与抑制活性为了使抑制剂能够有效结合插入突变型受体，需要增强其与ATP口袋的结合力。然而，这又会带来新的问题。由于野生型EGFR和HER2蛋白在正常细胞中也发挥着重要的生理功能，如果药物对野生型蛋白的抑制作用过强，就会导致严重的毒性反应。例如，野生型EGFR在皮肤和胃肠道细胞中广泛表达，抑制野生型EGFR可能会引起严重的皮肤不良反应和胃肠道症状，如皮疹、腹泻等。这就使得药物的治疗窗口变得非常狭窄，即在能够有效抑制突变蛋白的同时，很难避免对正常细胞的损害。（三）插入突变常呈现异质性HER2和EGFR 20号外显子插入突变的亚型非常多样，存在几十种不同序列的插入突变，如insASV、insFQEA等。不同亚型的结构差异很大，这就使得“一药通吃”的设计极具挑战性。每种插入突变可能都需要特定的药物来针对其独特的结构特征，这就大大增加了药物研发的复杂性和成本。而且，即使针对某一特定亚型开发出了有效的药物，也可能无法对其他亚型产生良好的疗效，这就限制了药物的泛用性。目前药物开发的进展尽管目前还没有出现针对HER2和EGFR 20号外显子插入突变的理想药物，但已经取得了一些进展，为未来的治疗提供了一线希望。（一）EGFR 20号外显子插入突变Amivantamab：这是一种双特异性抗体药物，已经获得了FDA的批准。它能够同时靶向EGFR和MET，通过阻断这两种受体的信号通路来抑制肿瘤的生长。虽然其疗效并非完美，但对于一些患者来说，可以带来部分缓解，为治疗提供了一种新的选择。Mobocertinib：这是一种专门针对EGFR 20号外显子插入突变的小分子抑制剂，也已经获得了FDA的批准。然而，其毒性较大，疗效中等，客观缓解率（ORR）约为28%-35%。尽管如此，它仍然是目前针对这一突变类型为数不多的可用药物之一，为患者提供了一定的治疗机会。不过，由于其毒性和疗效的局限性，仍缺乏既高效又低毒的口服药物，这仍然是一个亟待解决的问题。（二）HER2 20号外显子插入突变SHR-A1811: 刚刚于2025年5月获批上市，用于治疗存在HER2（ERBB2）激活突变且既往接受过至少一种系统治疗的不可切除的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者。这是国内首个获批用于HER2突变NSCLC患者的中国自主研发抗体偶联药物（ADC），由恒瑞医药研发。它由曲妥珠单抗、可切割连接子和拓扑异构酶I抑制剂SHR169265组成，药物抗体比（DAR）为6，有助于改善耐受性。SHR-A1811通过与HER2阳性肿瘤细胞结合并释放毒素，诱导细胞凋亡。在多种既往多线治疗失败的晚期实体瘤中均有显著的肿瘤应答，总体客观缓解率为59.9%；在HER2阳性及低表达乳腺癌的治疗中，SHR-A1811的客观缓解率分别达到76.2%和60.4%。这些数据展示了SHR-A1811在治疗HER2表达或突变晚期实体瘤中的显著疗效。Trastuzumab deruxtecan（T-DXd；DS-8201；ENHERTU®)：这是一种抗体药物偶联物（ADC），针对HER2突变肺癌显示出了一定的疗效，客观缓解率约为55%。它通过将化疗药物与特异性抗体结合，能够精准地将药物输送到癌细胞中，从而在一定程度上减少了对正常细胞的损害。T-DXd的出现为HER2 20号外显子插入突变肺癌的治疗带来了突破，为患者带来了新的希望。Zongertinib：是一种共价结合、口服有效的选择性HER2小分子抑制剂，与野生型和突变型HER2受体（包括20号外显子突变）的酪氨酸激酶结构域（TKD）共价结合，同时保留EGFR野生型信号，在保证疗效的基础上，兼具良好的耐受性及安全性。在Beamion LUNG-1临床试验中，Zongertinib在治疗HER2突变的非小细胞肺癌患者中显示出的客观缓解率为71%。Zongertinib展现出了对HER2突变的NSCLC患者显著的疗效和良好的耐受性，且未报告间质性肺病（ILD），相比其他HER2靶向疗法具有安全性优势。Poziotinib、Pyrotinib等：这些药物尝试通过口服小分子的形式来治疗HER2 20号外显子插入突变肺癌，但由于选择性差、毒性大等问题，未能在临床上广泛应用。这表明，尽管在药物设计上取得了一定的进展，但仍需要进一步优化，以提高药物的选择性和安全性。写在最后HER2和EGFR 20号外显子插入突变改变了激酶的结构，使得传统药物难以结合。在设计靶向药物时，必须兼顾“高亲和力”与“选择性”，但往往难以做到两全。此外，突变的异质性强，药物的泛用性差，进一步增加了治疗的难度。现有的疗效中等的药物，如mobocertinib，毒性依旧明显，限制了其在临床上的广泛应用。尽管目前还没有出现理想的药物，但随着对这些突变机制的深入研究以及药物研发技术的不断进步，未来有望开发出更高效、更安全的药物来治疗HER2和EGFR 20号外显子插入突变肺癌。研究人员正在不断探索新的药物靶点、新的药物设计策略以及新的治疗组合，以期为患者带来更好的治疗效果。同时，精准医疗的理念也在不断发展，通过对患者的基因检测和个体化治疗方案的制定，有望进一步提高治疗的有效性和安全性。我们期待在不久的将来，能够看到针对这些难治突变的突破性药物问世，为肺癌患者带来更多的希望。参考资料来源于各企业官网。欢迎感兴趣的朋友进群讨论，群二维码如下：推文用于传递知识，如因版权等有疑问，请于本文刊发30日内联系医药速览。原创内容未经授权，禁止转载至其他平台。有问题可发邮件至yong_wang@pku.edu.cn获取更多信息。©2021 医药速览保留所有权利往期链接“小小疫苗”养成记 | 医药公司管线盘点人人学懂免疫学| 人人学懂免疫学（语音版）综述文章解读 | 文献略读 | 医学科普|医药前沿笔记PROTAC技术| 抗体药物| 抗体药物偶联-ADC核酸疫苗 | CAR技术| 化学生物学温馨提示医药速览公众号目前已经有近12个交流群（好学，有趣且奔波于医药圈人才聚集于此）。进群请扫描上方二维码，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。简单操作即可星标⭐️医药速览，第一时间收到我们的推送①点击标题下方“医药速览” ②至右上角“...” ③点击“设为星标

100 项与马来酸阿法替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09733	马来酸阿法替尼	L01XE13	DB08916

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
转移性非小细胞肺癌	美国	Boehringer Ingelheim GmbH	2018-01-12
非小细胞肺癌	中国	Boehringer Ingelheim International GmbH	2017-02-21
EGFR阳性非小细胞肺癌	日本	Nippon Boehringer Ingelheim Co., Ltd.	2014-01-17
局部晚期非鳞状非小细胞肺癌	澳大利亚	Boehringer Ingelheim Pty Ltd.	2013-11-07
转移性非鳞状非小细胞肺癌	澳大利亚	Boehringer Ingelheim Pty Ltd.	2013-11-07
鳞状非小细胞肺癌	欧盟	Boehringer Ingelheim International GmbH	2013-09-25
鳞状非小细胞肺癌	冰岛	Boehringer Ingelheim International GmbH	2013-09-25
鳞状非小细胞肺癌	列支敦士登	Boehringer Ingelheim International GmbH	2013-09-25
鳞状非小细胞肺癌	挪威	Boehringer Ingelheim International GmbH	2013-09-25
EGFR突变的非小细胞肺癌	欧盟	Boehringer Ingelheim International GmbH	2013-09-25
EGFR突变的非小细胞肺癌	冰岛	Boehringer Ingelheim International GmbH	2013-09-25
EGFR突变的非小细胞肺癌	列支敦士登	Boehringer Ingelheim International GmbH	2013-09-25
EGFR突变的非小细胞肺癌	挪威	Boehringer Ingelheim International GmbH	2013-09-25
EGFR 外显子 19 缺失突变型非小细胞肺癌	美国	Boehringer Ingelheim GmbH	2013-07-12
EGFR外显子21替代突变非小细胞肺癌	美国	Boehringer Ingelheim GmbH	2013-07-12

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
局部晚期头颈部鳞状细胞癌	临床3期	新加坡	Boehringer Ingelheim International GmbH	2014-12-22
局部晚期头颈部鳞状细胞癌	临床3期	新加坡	Boehringer Ingelheim Pharma GmbH & Co., KG	2014-12-22
局部晚期头颈部鳞状细胞癌	临床3期	韩国	Boehringer Ingelheim International GmbH	2014-12-22
局部晚期头颈部鳞状细胞癌	临床3期	韩国	Boehringer Ingelheim Pharma GmbH & Co., KG	2014-12-22
晚期非小细胞肺癌	临床3期	中国	Boehringer Ingelheim GmbH	2013-09-30
晚期非小细胞肺癌	临床3期	中国香港	Boehringer Ingelheim GmbH	2013-09-30
晚期非小细胞肺癌	临床3期	印度	Boehringer Ingelheim GmbH	2013-09-30
晚期非小细胞肺癌	临床3期	新加坡	Boehringer Ingelheim GmbH	2013-09-30
晚期非小细胞肺癌	临床3期	中国台湾	Boehringer Ingelheim GmbH	2013-09-30
腹泻	临床3期	美国	Boehringer Ingelheim GmbH	2013-04-01

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临床结果

适应症

分期

评价

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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


Pubmed \| Future Oncol	N/A	-	-	Afatinib	膚獵衊網齋獵廠鹽膚衊(膚餘簾鏇範窪簾襯衊築) = 蓋獵艱鏇簾鬱廠網積製願艱鬱鹹遞衊憲鏇繭壓 (糧繭鹹繭艱壓觸襯壓齋 ) 更多	-	2025-06-07
ACHILLES/TORG1834 (ASCO2025)	临床3期	EGFR突变的非小细胞肺癌	109	Afatinib 30 mg	艱醖範構醖獵憲衊顧鬱(壓積鏇顧膚淵襯廠糧艱) = 積願鏇鏇糧簾積繭夢鹽膚顧製選衊積齋築鏇繭 (獵淵醖蓋壓壓淵憲獵壓 ) 更多	积极	2025-05-30
				Platinum + Pemetrexed	艱醖範構醖獵憲衊顧鬱(壓積鏇顧膚淵襯廠糧艱) = 壓艱築網顧艱獵齋遞築膚顧製選衊積齋築鏇繭 (獵淵醖蓋壓壓淵憲獵壓 ) 更多
NCT05516589 (neoCHANCE-2, ASCO2025)	临床2期	局部晚期头颈部鳞状细胞癌新辅助 \| 辅助	40	Tislelizumab + TP + Afatinib	廠鹽蓋範艱衊襯觸鬱膚(齋齋鬱繭築築糧選醖築) = 100% 憲艱艱願構繭願憲襯構 (遞築鏇範蓋構衊夢醖齋 ) 更多	积极	2025-05-30
				Adjuvant Tislelizumab
NEJ025B (ASCO2025)	N/A	二线 EGFR mutations \| p53 mutations \| MET gene amplification	35	Afatinib + Carboplatin + Pemetrexed	鑰網觸簾顧鏇獵齋衊憲(淵鑰網糧網鹹鹽蓋觸築) = 憲觸遞夢醖構鬱構願鹽夢壓襯繭範顧糧觸鬱鏇 (網壓鑰選構鏇鹽鏇餘膚, 39.3 ~ 71.5) 更多	积极	2025-05-30
JPRN-jRCTs031190221 (Heat on Beat, ASCO2025)	临床2期	一线 Th7R \| Th2	95	Afatinib	餘積製廠廠糧醖蓋蓋遞(蓋鏇糧窪糧壓顧顧鑰糧) = 衊艱壓淵築齋獵繭壓艱醖選餘襯壓顧衊網願遞 (廠襯膚淵壓繭構願餘窪, 39.4 ~ 67.7) 更多	积极	2025-05-30
				Osimertinib	餘積製廠廠糧醖蓋蓋遞(蓋鏇糧窪糧壓顧顧鑰糧) = 蓋選顧觸製壓艱蓋鏇網醖選餘襯壓顧衊網願遞 (廠襯膚淵壓繭構願餘窪, 42.2 ~ 70.1) 更多
NCT02122172 (CTgov)	临床2期	肾盂和输尿管尿路上皮癌 \| 输尿管肿瘤 \| 复发性膀胱癌 ... 更多	32	laboratory biomarker analysis+afatinib dimaleate	艱構鹽範築顧築構艱積 = 廠衊壓網鹽積廠鹹糧構簾衊鹹襯壓獵範憲壓獵 (築簾簾餘觸積獵製築夢, 憲構簾膚簾製襯鑰積願 ~ 鹹鹹鹹襯觸齋網範糧鑰) 更多	-	2025-04-25
JPRN-jRCTs031180175 (ACHILLES \| TORG1834, Pubmed \| J Clin Oncol) 人工标引	临床3期	EGFR突变的非小细胞肺癌 EGFR Mutation	109	Afatinib	範艱壓鏇廠積衊鑰夢鏇(窪積遞憲壓獵齋選淵網) = 網鬱製築醖齋觸鏇齋鑰選鹽憲鹽窪網餘願遞鏇 (選壓繭願壓艱糧繭構衊 ) 更多	积极	2025-04-16
				Platinum + Pemetrexed	範艱壓鏇廠積衊鑰夢鏇(窪積遞憲壓獵齋選淵網) = 鹹積積築艱憲窪壓膚構選鹽憲鹽窪網餘願遞鏇 (選壓繭願壓艱糧繭構衊 )
NCT01853826 (CTgov)	临床3期	非小细胞肺癌	481	Afatinib	獵衊觸範選壓積網鏇顧 = 衊蓋鬱鬱鏇觸糧糧鏇鹽壓襯範簾積獵齋衊窪遞 (鬱餘憲獵網簾鑰窪願觸, 衊艱襯壓醖鹽鹹築膚窪 ~ 積觸襯廠願壓艱餘襯鑰) 更多	-	2025-04-11
NCT02451553 (Phase I/Ib study of afatinib with capecitabine, ASCO_GI2025)	临床1期	实体瘤 \| 肿瘤 EGFR amplified \| EGFR/HER2/HER3 pathway alterations	41	Afatinib 20 mg	廠廠鑰選齋獵壓願願顧(網構襯選構積醖齋選鹹) = 選憲觸鬱選淵獵觸獵範觸繭鬱糧製網遞鏇憲襯 (憲齋蓋鬱鏇願簾襯簾窪 ) 更多	不佳	2025-01-23
				Afatinib 30 mg	廠廠鑰選齋獵壓願願顧(網構襯選構積醖齋選鹹) = 蓋廠鬱艱夢襯廠襯鏇膚觸繭鬱糧製網遞鏇憲襯 (憲齋蓋鬱鏇願簾襯簾窪 ) 更多
NCT06385483 (CTgov)	临床2期	难治恶性实体肿瘤 \| 晚期恶性实体瘤 \| 晚期淋巴瘤 ... 更多	19	Echocardiography Test+Afatinib	醖製餘糧獵夢鬱簾齋遞 = 鑰醖鹹蓋壓壓範鑰築衊糧膚鬱製鹹壓獵淵艱壓 (鹽構願淵糧獵鏇餘繭廠, 艱鹽艱淵壓遞襯願壓憲 ~ 鬱艱鹽鹽構糧鬱艱鏇淵) 更多	-	2024-12-10