Epidermal growth factor receptor (EGFR) signaling plays a key role in regulating epidermal cell proliferation, survival, and differentiation. Keratins form a scaffold with epidermal desmosomes that involves ErbB/ EGFR signaling and keratin deficiency makes keratinocytes more sensitive to EGFR activation. Erlotinib, an EGFR inhibitor, was approved 20 years ago for cancer treatment and is generally used at 150 mg daily in adults >50 kg. While gastrointestinal and cutaneous side effects commonly occur at doses of 150 mg, adverse events occur less often at lower doses. We first reported erlotinib as effective for Olmsted syndrome, a rare hereditary EDD with painful PPK that results from variants in TRPV3. Erlotinib is now the treatment of choice for children and adults with Olmsted syndrome. Erlotinib is thought to inhibit formation of a complex that includes TRPV3, EGFR, and its primary skin-based ligand, TGF-a, which in turn regulates keratinocyte proliferation and differentiation. High-throughput screening to identify compounds that stabilize keratin filaments have also pointed to the EGFR pathway for targeting. Reviews and recent case reports have suggested the benefit of erlotinib for PC,
Given these preliminary data, we hypothesize that EGFR activation is a characteristic feature of keratinopathies. Further, we expect that oral low-dose erlotinib will improve the scaling and skin thickening of the spectrum of keratinopathies and be tolerated by most patients. For those who experience pain, particularly from plantar involvement, we predict that erlotinib therapy will improve mobility and pain. Finally, we aim to find the mechanism by which erlotinib improves the phenotypes of the various keratinopathies to better understand these disorders and predict response. We will look specifically at the impact on differentiation vs. hyperproliferation and barrier function, as well as the immune modulatory effects of the erlotinib using a multi-omics approach.

开始日期2025-12-01

申办/合作机构

Northwestern University

[+1]

NCT04172779

/ Not yet recruiting临床2期IIT

Phase IIa Single-arm Clinical Trial of Hepatocellular Carcinoma Chemoprevention With Low-dose Erlotinib in Patients With Liver Cirrhosis

This phase IIa trial studies long-term low-dose erlotinib hydrochloride treatment to assess its efficacy and safety to prevent development of hepatocellular carcinoma in patients with liver cirrhosis.

开始日期2025-07-01

申办/合作机构

The University of Texas Southwestern Medical Center

[+1]

NCT06161558

/ Not yet recruiting临床1期IIT

Phase 1 Umbrella Trial of Erlotinib In Combination With Select Tyrosine Kinase Inhibitors In Adult Patients With Advanced Solid Tumors

Cancers that return or spread after their first line of treatment are often difficult to treat with limited next step options. Based on preclinical studies, the EGFR-targeting tyrosine kinase inhibitor (TKI) Erlotinib may be better in stopping or slowing the growth of tumors when given in combination with the multitargeting TKI Lenvatinib or Axitinib. Participants will be screened with a physical exam and tests including urine and blood tests, imaging scans, and a test of their heart function. Erlotinib, axitinib, and lenvatinib are all capsules taken by mouth. All participants will take their drugs at home every day. Some participants will take erlotinib plus lenvatinib once a day. Some participants will take erlotinib once a day and axitinib twice a day. Assignment to one of the treatment arms will be determined by the study. Participants will record their doses in a diary. Treatment is given in 28-day cycles. All participants will have 4 clinic visits during their first treatment cycle. After that, they will have a clinic visit at the start of each new cycle. Imaging scans, blood and urine tests, and other tests will be repeated during various clinic visits. Participants will remain in the study for as long as the treatment is helping them. They will have follow-up phone calls after they stop treatment....

开始日期2025-04-03

申办/合作机构

National Cancer Institute

100 项与盐酸厄洛替尼相关的临床结果

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100 项与盐酸厄洛替尼相关的转化医学

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100 项与盐酸厄洛替尼相关的专利（医药）

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11,925

项与盐酸厄洛替尼相关的文献（医药）

2025-05-24·Journal of biomolecular structure & dynamics

Design, synthesis, molecular modeling, and biological evaluations of novel chalcone based 4-Nitroacetophenone derivatives as potent anticancer agents targeting EGFR-TKD

Article

作者: Khan, Andleeb ; Abdulaal, Wesam H. ; Khan, Mohammad Imran ; Mir, Showkat Ahmad ; Meher, Rajesh Kumar ; Nayak, Binata ; Baitharu, Iswar ; Murmu, Narayan

A series of chalcone-based 4-Nitroacetophenone derivatives were designed and synthesized by the single-step condensation method. These compounds were identified by ¹H NMR,¹³C NMR, MS, and FTIR analysis. Further, the derivatives were evaluated against four cancer cell lines H1299, MCF-7, HepG2, and K526. The IC₅₀ value of potent compounds NCH-2, NCH-4, NCH-5, NCH-6, NCH-8, and NCH-10 was 4.5-11.4 μM in H1299, 4.3-15.7 μM in MCF-7, 2.7-4.1 μM in HepG2 and 4.9-19.7 μM in K562. To assess the toxicity against healthy cells all potent molecules were evaluated against the HEK-293T cell line, and IC₅₀ values exhibited by NCH-2, and NCH-3 were 77.8, 74.3, and other molecules showed IC₅₀ values > 100 μM. The EGFR expression was determined by using rabbit anti-EGFR monoclonal antibody and significant EGFR expression was knocked down observed in H1299 treated with NCH-10 as well as erlotinib. The underlying mechanism behind cell death was investigated through bioinformatics. First, the molecules were optimized and docked to the binding site of the EGFR kinase domain. The best complexes were simulated for 100-ns and compounds NCH-2, NCH-4, and NCH-10 achieved stability similar to the erlotinib bound kinase domain. The free energy binding (ΔG_bind) of NCH-10 was found to be more negative -226.616 ± 2.148 kJ/mol calculated by Molecular Mechanics Poisson Boltzmann's Surface Area (MM-PBSA) method. Both in vitro and in silico results conclude that the present class of chalcone-based 4-Nitroacetophenone derivatives are potent anti-cancer agents targeting EGFR-TKD and are 39 folds more effective against H1299, MCF-7, HepG2, and K562 carcinoma cell lines than healthy HEK-293T cell lines.

2025-05-01·BIOORGANIC CHEMISTRY

Design, synthesis, and biological evaluation of novel amidoxime or amidine analogues of some 4-anilino-6,7-dimethoxyquinazolines with a potent EGFR inhibitory effect

Article

作者: Çelik, İsmail ; Altuntaş, Tunca Gül ; Göker, Hakan ; Kütük, Özgür ; Acar Halıcı, Cemre

A series of 6,7-dimethoxy-4-anilinoquinazoline derivatives, which have amidine (4a-4d, 5a-5c, 6a-6d) and amidoxime (4e, 5d, 6e) moieties, were synthesized and evaluated their anticancer activity on various cancerous cell lines (H1975, HCC827, and H23). Among the synthesized compounds, 4c was found to be the most potent inhibitor of EGFR, comparable to erlotinib, with higher than 10 μM EC₅₀ values for H1975 and H23 and 0.16 μM EC₅₀ value for HCC827 cells. 4c activated mitochondrial apoptosis signaling and suppresses EGFR downstream signaling, such as ERK1/2 and PI3K/Akt pathways in HCC827 NSCLC cells (EGFR Del19) as erlotinib. Molecular docking and molecular dynamics simulations studies were performed to evaluate the interaction and binding energies of all synthesized compounds against EGFR wild type, EGFR T790M/L858R, EGFR L858R, and EGFR exon-19 deletion mutant (del-747-749). 4c showed a similar binding profile with erlotinib as stable binding interaction values. Also, 4c formed additional hydrogen bonds via the amidine group in its structure, potentially increasing its affinity and stability within the binding pocket. Hence, 4c was selected as a lead compound for further pharmacomodulation.

2025-04-01·JOURNAL OF MOLECULAR STRUCTURE

Anticancer activity of fused quinazoline-quinazolinone: Synthesis, biological evaluations, and computational studies

作者: Sidek, Fatin Nur Elyana Mohd ; Goh, Bey Hing ; Ariffin, Azhar ; Keflee, Rashidi Dzul ; Daker, Maelinda ; Marzuki, Marini ; Abdulwahab, Muhammad Kumayl ; Halim, Siti Nadiah Abdul ; Norazit, Anwar ; Adzrill, Muhammad Hakim Muhamad ; Noor, Suzita Mohd ; Tan, Yee Seng

Although several methods for the synthesis of the fused quinazoline-quinazolinone derivatives have been reported, their biol. activity has not been thoroughly investigated.The objectives of the present study were to synthesize a series of fused quinazoline-quinazolinone derivatives and evaluate them for their anticancer activity alongside their potential as EGFR inhibitors, through in vitro, in vivo and in silico studies.This study presents the synthesis, biol. evaluation, and computational anal. of a series of quinazoline-quinazolinone fused ring derivatives as potential epidermal growth factor receptor (EGFR) inhibitor targeting non-small cell lung cancer (NSCLC).Compounds 3a-e were synthesized through the cyclization of quinazolinone with resp. aldehydes, yielding new quinazoline ring.Compound 3b recorded significant activity against H1975 cells (IC₅₀ = 15.9 ± 1.2 μM) and moderate activity against A549 cells (IC₅₀ = 32.9 ± 1.2 μM) in the MTT assay, compared to gefitinib (IC₅₀ = 20.2 ± 1.1 μM and 34.0 ± 1.2 μM, resp.).It also inhibited EGFR and PI3K enzymes at 10 μM in the Western Blot assay.The compound induced apoptosis and cell cycle arrest at the G0/G1 phase in H1975 cells.Addnl., the fish embryo acute toxicity assay showed that the compound was non-toxic at 400 μM on zebrafish embryos.In silico studies using mol. docking and mol. dynamics revealed that the binding of the compound to EGFR was stabilized by hydrophobic and hydrogen bonding interactions.These results suggest that the quinazoline-quinazolinone derivative holds promise as an EGFR inhibitor and warrants further investigation.

376

项与盐酸厄洛替尼相关的新闻（医药）

2025-04-01

·正大天晴药业集团

2025 ELCC | 安罗替尼联合治疗如何“精准制导”EGFR突变晚期非小细胞肺癌？

2025年欧洲肺癌大会（ELCC）上，正大天晴1类创新药安罗替尼联合EGFR-TKI治疗非小细胞肺癌的三项前瞻性临床研究入选壁报展示，为A+T（安罗替尼联合EGFR-TKI）联合方案治疗EGFR敏感突变晚期非小细胞肺癌（NSCLC）再添新的循证依据。肺癌是引起人类恶性肿瘤相关性死亡的首要原因，其中NSCLC是肺癌的主要类型，对全球疾病发病率和死亡率有着极其重要的影响。表皮生长因子受体（EGFR）突变作为非小细胞肺癌的重要驱动基因，亚裔人群和我国的肺腺癌患者EGFR基因敏感突变阳性率为40-50%，尽管目前EGFR酪氨酸激酶抑制剂（EGFR-TKIs）靶向药物能够显著改善EGFR敏感突变晚期NSCLC患者的临床获益，但EGFR-TKIs耐药问题与EGFR 19del或L858R等特定亚型的疗效差异仍是临床痛点[1-3]。既往多项研究表明抗血管生成药物联合EGFR-TKI（A+T联合方案）具有协同增效作用[4-9]。本次大会上公布的安罗替尼联合EGFR-TKI治疗EGFR-TKIs耐药、EGFR 19del或L858R突变晚期NSCLC三项研究，有望为广大患者带来新的治疗希望。1.安罗替尼联合舒沃替尼治疗EGFR-TKIs耐药EGFR突变晚期非小细胞肺癌患者的II期研究（WU-KONG9）67P - A Phase II Study of Sunvozertinib Combined with Anlotinib in EGFR-TKIs resistant EGFRm Advanced NSCLC Patients（WU-KONG9）通讯作者：复旦大学附属中山医院胡洁第一作者：复旦大学附属中山医院胡洁内容概要：该研究为一项开放标签、单臂、II期研究，旨在评估安罗替尼联合舒沃替尼用于治疗EGFR-TKI耐药的EGFR突变晚期NSCLC患者临床效果。主要终点为客观缓解率（ORR），次要终点包括疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）及安全性。新增基于二代测序（NGS）和类器官药物敏感性评估的探索性终点，以探索耐药机制。截至2024年12月25日，10例患者完成剂量递减安全导入，3例进入剂量扩展阶段。舒沃替尼联合安罗替尼耐受性良好，未发生剂量限制性毒性（DLT）事件，最终确定推荐联合剂量（RCD）为舒沃替尼300 mg（qd），联合安罗替尼12 mg（qd，d1-14，q3w）。12例患者完成首次疗效评估，ORR为33.3%，DCR达100%。研究表明，舒沃替尼联合安罗替尼耐受性良好，在EGFR-TKI治疗失败的EGFR突变NSCLC患者中显示出潜在抗肿瘤活性。目前研究正在持续入组中。2.安罗替尼联合伏美替尼用于一线治疗EGFR L858R突变的晚期非小细胞肺癌75P - Firmonertinib plus anlotinib for first-line treatment of advanced EGFR L858R mutated non-small cell lung cancer通讯作者：四川省肿瘤医院周进第一作者：四川省肿瘤医院周进内容概要：该研究为一项前瞻性、多中心、II期临床研究，旨在探索伏美替尼联合安罗替尼作为一线方案治疗晚期EGFR L858R突变NSCLC的临床效果。主要终点为ORR，次要终点包括PFS、DCR、安全性及患者报告结局（PRO）等。研究还将探索性分析治疗3周后循环肿瘤DNA（ctDNA）状态对预后的影响。截至2025年1月10日，共入组16例患者并接受治疗，其中，11例患者完成至少一次疗效评估，中位随访时间255天，中位PFS尚未达到。研究者基于RECIST v1.1标准评估的ORR为90.9%，DCR为100%，中位缓解深度（DpR）为41.1%。治疗3周后4例患者实现ctDNA清除，此4例患者DpR相对较高，分别为79.4%、67.5%、46.3%和45.9%，证明伏美替尼联合安罗替尼一线对肿瘤有显著的抑制作用。目前正在进行长期随访以进一步评估生存结局。3.安罗替尼联合伏美替尼治疗初治EGFR突变非小细胞肺癌患者：FOCUS-A研究更新结果62P - Firmonertinib (formerly furmonertinib) combined with anlotinib in patients with treatment-naive EGFR-mutant non-small-cell lung cancer: updated results from FOCUS-A study通讯作者：上海交通大学附属胸科医院韩宝惠第一作者：上海交通大学附属胸科医院韩宝惠内容概要：该研究为一项单臂、多中心、前瞻性Ⅱ期临床研究，旨在探索伏美替尼联合安罗替尼在初治EGFR突变NSCLC患者中的抗肿瘤活性与安全性。主要终点为研究者评估的ORR。次要终点为PFS、DCR和安全性等。截至2024年12月6日，共纳入40例患者，中位随访时间27.8个月。总体ORR为87.5%，DCR为100%，中位PFS为25.1个月。18例外显子19缺失突变患者ORR为77.8%，确认的ORR为77.8%，中位PFS未达到；22外显子21 L858R突变患者ORR为95.5%，确认的ORR为81.8%，中位PFS为19.0个月；在16例基线存在中枢神经系统（CNS）转移的患者中，ORR为87.5%，DCR为100%，中位DpR为50.39%，中位PFS为25.1个月。CNS转移患者中，外显子19缺失突变与外显子21 L858R突变患者的中位PFS无显著差异（未达到 vs. 25.1个月）。16例基线存在CNS转移患者的中位CNS-PFS为33.2个月。数据显示，安罗替尼联合伏美替尼方案在实验人群中展现出持久的抗肿瘤活性及可耐受的安全性，有望为EGFR突变NSCLC患者提供新的用药方案。一直以来，正大天晴以未被满足的临床需求为导向，不断在肿瘤领域深耕。未来，期待开展更多A+T模式临床探索，为EGFR敏感突变晚期NSCLC的精准治疗提供更多循证证据。参考文献：[1]中国临床肿瘤学会（CSCO）非小细胞肺癌诊疗指南2024[2]Wang Z, Cheng Y, An T, et al. Detection of EGFR mutations in plasma circulating tumour DNA as a selection criterion for first-line gefitinib treatment in patients with advanced lung adenocarcinoma (BENEFIT): a phase 2, single-arm, multicentre clinical trial. Lancet Respir Med. 2018;6(9):681–90. [3]Hong S, Gao F, Fu S, et al. Concomitant genetic alterations with response to treatment and epidermal growth factor receptor tyrosine kinase inhibitors in patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer. JAMA Oncol. 2018;4(5):739–42.[4]Kawashima Y, Fukuhara T, Saito H, et al. Bevacizumab plus erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Respir Med. 2022 Jan;10(1):72-82. [5]Zhou Q, Xu CR, Cheng Y, et al. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell. 2021 Sep 13;39(9):1279-1291.e3.[6]Zhang L, Wang L, Wang J, et al. Anlotinib plus icotinib as a potential treatment option for EGFR-mutated advanced non-squamous non-small cell lung cancer with concurrent mutations: final analysis of the prospective phase 2, multicenter ALTER-L004 study. Mol Cancer. 2023 Aug 5;22(1):124.[7]Zhao H, Yao W, Min X, et al. Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706). J Thorac Oncol. 2021 Sep;16(9):1533-1546. doi: 10.1016/j.jtho.2021.05.006. Epub 2021 May 24. PMID: 34033974.[8]Ponce Aix S, Novello S, Garon EB, et al. RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated, EGFR-mutated, metastatic non-small cell lung cancer: Europe/United States subset analysis. Cancer Treat Res Commun. 2021;27:100378. [9]Zhao H, Yao W, Min X, et al. Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706). J Thorac Oncol. 2021 Sep;16(9):1533-1546. doi: 10.1016/j.jtho.2021.05.006. Epub 2021 May 24. PMID: 34033974.▲ 上下滑动查看更多声明：1.新闻稿旨在促进医药信息的沟通和交流，仅供医疗卫生专业人士参阅，非广告用途。2.本公司不对任何药品和/或适应症作推荐。3.本新闻稿中涉及的信息仅供参考，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。若您想了解具体疾病诊疗信息，请遵从医生或其他医疗卫生专业人士的意见或指导。● 谢承润受邀参加中国发展高层论坛为生物医药产业发展积极建言● 中国生物制药2024全年业绩发布：营收净利双双实现两位数增长创新产品收入突破120亿创新高● 在妇科肿瘤领域创新突破，正大天晴双星闪耀2025 SGO● 多类型肿瘤高表达！正大天晴FGFR2b单抗首次获批临床

临床2期临床结果

2025-03-31

·BiG生物创新社

EGFR突变NSCLC进入“排列组合”时代

作者｜Bio-three肺癌尤其是非小细胞肺癌（NSCLC），目前是全球癌症领域中最大的健康挑战。根据 Cancer.Net 编辑委员会报道，2023 年美国的新发病例达到238,340 例，死亡病例达到127070 人。NSCLC 约占所有肺癌病例的 85%，主要分为腺癌、鳞状细胞癌或大细胞癌。手术干预仍然是早期NSCLC （I 至 II 期）诊断患者的金标准，然而复发的风险仍然存在，术后五年内复发率在 30% 至 55% 之间波动。表皮生长因子受体（EGFR）基因是 NSCLC 病理发展的关键参与者，总体发生率为 17.2%。但在中国在内东南亚地区，它的患病率则高达40%~60%。厄洛替尼、吉非替尼和表奥希替尼等多种皮生长因子受体酪氨酸激酶抑制剂（EGFR TKI），已成为具有 EGFR 致敏突变的晚期非小细胞肺癌（NSCLC）患者的标准治疗方法，但耐药性通常在10至14个月后发生。耐药机制的机制多种多样，最明显的是 EGFR 基因获得继发突变，改变 EGFR 蛋白结构，增强其 ATP 亲和力，降低EGFR TKI的疗效，促进肿瘤增殖。此外如MET基因替代途径的激活，绕过了EGFR TKI的作用，确保癌细胞的持续生长和存活。HER3虽然缺乏内在激酶活性，但在与其他受体（如HER2、EGFR和MET）异二聚化后成为有效的信号转导实体。这些异二聚体充当复杂的分子开关，可以参与各种细胞内信号转导级联反应，有助于形成强大而有弹性的增殖信号网络，从而增强细胞承受靶向治疗的能力。NSCLC 中 EGFR TKI 耐药机制总结（Front. Immunol. 14:1332057）因此EGFR、MET和HER3三个靶点，成为解决EGFR突变非小细胞肺癌耐药的主要途径，但至少需要两个靶点的阻断才能一定程度解决耐药，因此双抗ADC药物的开发成为可能，并持续活跃，EGFR突变非小细胞肺癌由此也开始进入靶点的排列组合阶段，本文简要进行总结。EGFR、c-Met和HER3相关靶点双抗ADCEGFR/HER3双抗ADC百利天恒全球首创的EGFR/HER3双抗ADC药物BL-B01D1，是最早尝试这个策略的。百利天恒认为，EGFR可以和多种配体结合，且一旦内吞，配体-受体复合物可以循环到细胞表面。EGFR/HER3双抗ADC通过结合两个受体更好地调节细胞内运输，从而增强有效载荷的细胞内释放，显著克服耐药性。BL-B01D1代谢特性（百利天恒招股说明书）在结构设计方面，两个靶点的抗体采用了差异化的亲和力设计，以提高其偏向性的结合能力，同时Fc区域采用的野生性的IgG1，通过Fc的效应细胞改善药物分布以及提高免疫反应。ADC设计方面，此在采用自主开发的拓扑异构酶毒素Ed-04，在第一三共的Dxd的α亚酰氨处进行了改进，连接子采用GGFG，DAR值为8。BL-B01D1结构与功能（修改于百利天恒官网官网）BL-B01D1于2021年11月开始开展首次人体I期临床研究，2023年ASCO会议期间，BL-B01D1首次公布了人体I期临床研究结果。在38例EGFR突变的非小细胞肺癌患者中取得了63.2%的响应率，特别是还有34例患者接受过第三代EGFR TKI治疗，其也成为迄今为止EGFR突变的非小细胞肺癌最高的响应率，显著高于HER3 ADC、EGFR ADC和EGFR/c-Met双抗等新型疗法。BL-B01D1非小细胞肺癌临床数据比较（百利天恒招股说明书）基于BL-B01D1颠覆性的临床数据，2023年12月，百利天恒和百时美施贵宝宣布关于EGFRxHER3双抗ADC BL-B01D1，达成8亿美金首付款机潜在总价值84亿美元的交易，创造了迄今为止全球ADC领域单个资产总交易额最大的全球战略许可及合作交易，也掀开了相关靶点的ADC药物的研发序幕。普米斯是第二家公开EGFR/HER3双抗ADC药物研发的，2024 AACR期间其公开了一款临床前的EGFR/HER3双抗ADC药物PM1300，但一直还未推进到临床阶段。双抗结构方面，PM1300具有非对称的1+1 IgG样结构，这种结构使得PM1300能够优先结合EGFR/HER3双阳性癌细胞，而不是EGFR单阳性细胞，这可能显著降低EGFR靶向药物常见的安全风险。PM1300通过在每个结合臂的CH1-CL域引入独特突变，避免HC-LC错配，还在每个CH3域引入了KIH突变，以支持HC/HC异二聚体化。ADC的构建方面，采用可切除的连接子和拓扑异构酶毒素抑制偶联，DAR值为8。PM1300临床前初步信息（AACR 2024）映恩是第三家公开EGFR/HER3双抗ADC药物研发的，虽然DB-1418还处在临床前，但2024年1月7日，映恩生物就以5000万美元预付款，约11.5亿美元里程碑金额，将将该款药物的大中华区外全球权益授权给Avenzo Therapeutics。DB-1418通过一个可裂解连接子与拓扑异构酶I抑制剂有效载荷P1021结合而组成，DAR值差异性地设置为6。同时还和百利天恒采用了差异化的1+1的二价抗体结构设计，避免了EGFR的过强激活，特别是是在亲和力设计方面具有显著差异。DB-1418产品结构（映恩专利WO2025016453）具体来看，映恩双抗与人EGFR亲和力，比百利天恒的对照抗体SI-1X6.4弱约15倍，而与HER3的亲和力比对照抗体SI-1X6.4强25倍。这样的双抗亲和力设计可以减少双抗对广泛分布表达的表达EGFR正常组织的在靶毒性。DB-1418靶点亲和力（映恩专利WO2025016453）在奥希替尼耐药的非小细胞肺癌模型中，相同的给药剂量下的DB-1418比百利的双抗ADC（ADC-14）显示更强的抗肿瘤活性。 DB-1418临床前结果（映恩专利WO2025016453）除了百利天恒和映恩生物，君实生物EGFR/HER3的双抗ADC药物JS212已经获批进入临床，但还未透露任何产品信息。此外，在2025年JPM会议中，信达生物公开了IBI3005为一款EGFR/HER3 ADC药物，目前正在进行一项一期临床爬坡试验，探索剂量范围为0.5~15 mg/kg。信达生物的临床ADC药物管线（JPM 2025）此外，劲方医药不仅仅考虑大分子靶点的协同性，同时还是考虑荷载的协同性。将泛RAS抑制剂通过连接子与EGFR/HER3双抗缀合，充分利用抗体靶向肿瘤细胞的特异性以及RAS抑制剂的高效性，同时降低或避免其对正常组织细胞的毒副作用。劲方医药泛RAS ADC药物专利示例之一（劲方医药专利WO2025049345）同时，近期AACR 2025摘要公开，四家公司又公开了EGFR\HER3双抗ADC的研发，康宁杰瑞更是将EGFR/HER3卷向了双抗双荷载ADC药物。其构建的EGFR/HER3双抗ADC药物JSKN021，分别通过可切割接头与 Fc 上的聚糖，等比例偶联拓扑异构酶抑制剂毒素T01（Alphatecan）和微管抑制剂毒素MMAE，DAR值为6（4+2）。JSKN021 抑制 Her3 或两种表达的癌细胞的生长，例如 HCC827、MDA-MB-468、A431 和 NCI-H1975。此外，在多个 CDX 模型中，JSKN021 显示出比单有效载荷 ADC 更强的肿瘤抑制效果。JSKN021示意图（康宁杰瑞官网）EGFR/c-Met双抗ADC此前强生开发的EGFR/c-Met双抗药物Amivantamab (JNJ-61186372)，成为科学上最为突出的双抗药物之一。基于独创性的生物学机制，目前已经先后斩获多个EGFR突变的肥效细胞肺癌二线单药，以及一线联合治疗方案。Amivantamab (JNJ-61186372)的生物学机制（Clinical Lung Cancer, Vol. 24, No. 2, 89–97）面对Amivantamab的巨大成功，多个公司采用了EGFR/c-Met双抗ADC的迭代研发策略。阿斯利康最早进行了迭代，2023年AACR会议上，其首次公布EGFR/c-Met双抗ADC药物AZD9592，目前其处于临床一期研发阶段。AZD9592的采用了其独有的Duetmab平台防止轻链错配，重链部分采用了KIH技术防止错配，非对称的二价结构。亲和力方面，c-Met端比EGFR端高15倍。ADC构建方面，采用其平台的拓扑异构酶抑制剂毒素SG3932。为了更进一步的基于Cys定点偶联考虑，采用了Thiomab技术，在Fc原本S239的位置做了C239插入突变的改造，DAR值最终为6。AZD9592的产品结构（阿斯利康专利US20230183358A1）临床前的结果显示，AZD9592对于EGFR或MET基因扩增和突变的肿瘤模型中，均显示出显著疗效，未来临床结果值得期待。AZD9592的临床前体内结果（阿斯利康官网）百奥赛图赛图开发的DM005为一款全人EGFR/c-Met双抗ADC，DM005骨架由百奥赛图共同轻链全人抗体鼠Renlite产生。ADC构建方面，DM005使用的Linker-Payload为拓扑异构酶抑制剂类毒素分子BLD1102。DM005独特设计的可裂解linker具有优异亲水性，赋予ADC如单抗般优秀的亲水性质，极大地改善ADC的理化性质，表现出高度的血浆稳定性及高效的肿瘤杀伤。DM005在非小细胞肺癌PDX模型中抗肿瘤效果（多玛生物官网）2024年AACR期间，普方生物也汇报了一款EGFR/c-Met双抗PRO1286临床前数据，其采用其独有亲水性连接子和exatecan毒素，DAR值为8，临床前数据显示PRO1286表现出广泛的抗肿瘤活性和良好的耐受性，目前已经推进至临床一期。PRO1286的临床前信息（AACR 2024）2024年11月，安领科生物在clinical trials网站上，登记了一项EGFR/c-Met双抗ADC药物ALK202，在多种晚期实体瘤患者中启动一项1期临床试验。早在2024年3月21日，君实生物和安领科生物联合申请的喜树碱ADC专利（WO 2024056101 A1）已经公开，其发明点主要在连接子，主链部分引入亲水结构，Payload大概率采用已知毒素DXd或Exatecan等。如果2024年还仅是EGFR/c-Met双抗ADC药物的萌发阶段，2025则进入快速发展阶段，仅刚刚公布的2025 AACR摘要中就公开了5款相关药物的开发，未来势必进入更为激烈的竞争阶段。HER3/c-Met双抗ADCEGFR、c-Met和HER3三个靶点，从排列组合的角度，除了以上两组形式，显然只剩下HER3/c-Met。2023年AACR期间，百奥赛图公布了全球首款HER3/c-Met双抗ADC药物的研发BCG022，其同样由共同轻链全人抗体鼠Renlite产生，通过亲水性的连接子搭载拓扑异构酶抑制剂毒素BLD1102，DAR值为8。在临床前的PDX模型中，展现出良好的抗肿瘤作用。BCG022抗肿瘤效果（百奥赛图官网）近期恒瑞公开了HER3/c-Met双抗ADC专利，同时该款药物SDP01873也入选了2025 AACR演讲环节，成为全球第二款公开的HER3/c-Met双抗ADC。此前恒瑞管线中分别HER3和c-Met单抗的ADC，在构建双抗之前，恒瑞分别对之前的HER3和MET单抗都进行了突变升级，以实现新的生物学功能。双抗的结构方面，恒瑞采用了1+1的非对称结构，这样也避免了双价c-Met带来的激活作用。重链方面采用Knob in hole防止错配，轻链方面采用了自主的Obscurin-O/CH1交换策略防止错配，设计了2232-01和2232-02两个候选双抗。恒瑞SDP01873双抗构型（专利WO2025056029）磷酸化水平显示，抗HER3抗体A不会引起ERK磷酸化，抗HER3/MET双特异性抗体 2232-01未明显引起ERK磷酸化。表明抗HER3/MET双特异性抗本不会引起 HER3/MET靶点二聚化激活下游信号通路。恒瑞SDP01873磷酸化功能（专利WO2025056029）ADC的构建方面，用可裂解四肽连接子GGFG和新型拓扑异构酶I抑制剂载荷（SHR9265）组成，DAR值为6，2232-01和2232-02双抗对应的ADC分别为ADC-1和ADC-2。恒瑞SDP01873双抗ADC结构（专利WO2025056029）构建ADC后对两个抗原的亲和力没有影响，MET和HER3两者亲和力相近，均为两位数的nM水平。恒瑞SDP01873双抗亲和力（专利WO2025056029）体内奥希替尼耐药的非小细胞肺癌肿瘤模型中，ADC-1和ADC-2均表现出显著的肿瘤抑制作用，并且对小鼠体重没有显著影响，未来临床值得期待。恒瑞SDP01873双抗ADC临床前抗肿瘤效果（专利WO2025056029）结语总体来看，EGFR、MET和HER3三个靶点相关的双抗ADC，除了EGFR/HER3的一款药物产生了临床数据，其它还都处于早期研发阶段，但是已经进入较为激烈的开发阶段，未来竞争将十分激烈。相关项目看似排列组合一般，实际背后也蕴藏着多重临床机制的探索与转化，未来充满期待。如上所述，目前仅有BL-B01D1产生临床数据，未来这些药物的开发仍然充满着高度的不确定性。从目前的趋势来看，除了这三个靶点，TROP-2和HER2等其它靶点将进一步丰富组合的多样性，不仅仅有望为基因突变的非小细胞肺癌带来突破，也有望在多种实体瘤取得进展。共建Biomedical创新生态圈！如何加入BiG会员？

抗体药物偶联物申请上市

2025-03-26

·PipelineReview

RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) outperforms osimertinib with a significant and unprecedented overall survival benefit in patients with EGFR-mutated non-small cell lung cancer

Median overall survival not yet reached with projected improvement of more than one year versus osimertinib RARITAN, NJ, USA I March 26, 2025 I Johnson & Johnson (NYSE: JNJ ) today announced results for the gold standard endpoint in cancer treatment of overall survival (OS) from the Phase 3 MARIPOSA study. Head-to-head comparison data versus osimertinib showed RYBREVANT ® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) significantly extended OS in the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR ) exon 19 deletions (ex19del) or L858R substitution mutations. Median OS is projected to exceed one year beyond the median of three years observed with osimertinib and has not yet been reached. This is the first and only study to show a statistically significant and clinically meaningful OS improvement over osimertinib. New compelling data were presented during a proffered paper session at the 2025 European Lung Cancer Congress (ELCC) (Abstract #4O). 1 “The survival curve tells a clear story. RYBREVANT plus LAZCLUZE helps patients live longer, and the benefit keeps growing over time,” said trial investigator Professor Nicolas Girard*, M.D., Ph.D., Head of Medical Oncology, Institut Curie, and Professor of Thoracic Oncology and Respiratory Medicine at the Paris-Saclay University, France. “We see the gap between the survival curves continue to widen, which is exactly what we want to see in lung cancer treatment to improve outcomes for patients. These results reinforce that we are entering a new era for EGFR -mutated non-small cell lung cancer; with this evidence in hand, we need to ensure every patient gets the most effective treatment in the first line for the best possible chance at longer survival.” Unlike progression-free survival (PFS), which tracks the time a treatment keeps a patient’s cancer from progressing, OS helps patients understand the impact therapy could have on the ability to live longer from the start of treatment. Extending life expectancy is the most meaningful indicator of a treatment’s impact. At a median follow-up of 37.8 months, patients treated with the chemotherapy-free regimen of first-line RYBREVANT ® plus LAZCLUZE™ had a significantly longer OS compared to those receiving osimertinib (hazard ratio [HR], 0.75; 95 percent confidence interval [CI], 0.61-0.92; nominal P<0.005). Median OS for RYBREVANT ® plus LAZCLUZE™ has not yet been reached, indicating that survival benefits continue to extend beyond the measured follow-up period (not reached [NR]; 95 percent CI, 42.9-NR). Comparatively, median OS for osimertinib-treated patients was 36.7 months (95 percent CI, 33.4-41.0) and consistent with prior studies with osimertinib. Fifty-six percent of patients treated with RYBREVANT ® and LAZCLUZE™ were alive at three and a half years compared to 44 percent of patients on osimertinib. Projections based on survival data suggest RYBREVANT ® plus LAZCLUZE™ could extend median OS by at least 12 months compared to osimertinib. 1 The RYBREVANT ® combination also prolonged multiple secondary endpoints vs osimertinib, including intracranial PFS, intracranial duration of response (DOR) and intracranial overall response rate (ORR). Notably, RYBREVANT ® plus LAZCLUZE™ prolonged time to symptomatic progression (TTSP) – the time from treatment randomization to the onset of lung cancer symptoms – by more than 14 months compared to osimertinib (43.6 months vs 29.3 months; HR, 0.69; 95 percent CI, 0.57–0.83; nominal P<0.001). This is a key patient-centered measure, highlighting how long quality of life can be preserved before lung cancer symptoms emerge. 1 “Right now, only twenty percent of patients with EGFR- positive NSCLC survive beyond five years. These MARIPOSA results suggest that RYBREVANT plus LAZCLUZE can change this dire statistic that has been stagnant for far too long,” said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. “This regimen isn’t just extending survival, it’s offering hope. By using RYBREVANT plus LAZCLUZE first, we’re delaying the need for chemotherapy and giving patients and their families more time.” The safety profile of RYBREVANT ® plus LAZCLUZE™ was consistent with the primary analysis, with adverse event (AE) rates comparable to other RYBREVANT ® regimens. No new safety signals were identified with the additional longer-term follow-up. Most AEs occurred early during RYBREVANT ® and LAZCLUZE™ treatment. 1 RYBREVANT ® research findings suggest that implementing prophylactic measures during the first four months of RYBREVANT ® and LAZCLUZE™ treatment may significantly reduce the risk of skin reactions, infusion-related reactions and venous thromboembolic events. 2,3,4 The MARIPOSA study met its primary endpoint in October 2023, showing a statistically significant and clinically meaningful improvement in PFS compared to osimertinib. RYBREVANT ® plus LAZCLUZE™ is approved in the United States, Europe and other markets around the world for patients with first-line EGFR -mutated NSCLC. These OS results will be shared with health authorities globally. About the MARIPOSA Study MARIPOSA ( NCT04487080 ), which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT ® in combination with LAZCLUZE™ versus osimertinib and versus LAZCLUZE™ alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or substitution mutations. The primary endpoint of the study is PFS (using RECIST v1.1 guidelines**) as assessed by BICR. Secondary endpoints include OS, ORR, DOR, PFS2 and intracranial PFS. 5 About RYBREVANT ® RYBREVANT ® (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S. , Europe and other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. 6 RYBREVANT ® is approved in the U.S. , Europe and other markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test. RYBREVANT ® is approved in the U.S., Europe and other markets around the world in combination with LAZCLUZE™ (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test. RYBREVANT ® is approved in the U.S. , Europe and other markets around the world in combination with chemotherapy (carboplatin-pemetrexed) for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR TKI. In February 2025, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of SC amivantamab and LAZCLUZE™ in Europe for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy. The National Comprehensive Cancer Network ® (NCCN ® ) Clinical Practice Guidelines in Oncology (NCCN Guidelines ® ) for NSCLC § prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include: In addition to the Phase 3 MARIPOSA Study, RYBREVANT ® is being studied in multiple clinical trials in NSCLC, including: For more information, visit: https://www.RYBREVANT.com . About LAZCLUZE™ In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of LAZCLUZE™ (marketed as LECLAZA in South Korea). LAZCLUZE™ is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR . An analysis of the efficacy and safety of LAZCLUZE™ from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023. 21 About Non-Small Cell Lung Cancer Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases. 22,23 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. 24 Among the most common driver mutations in NSCLC are alterations in EGFR , which is a receptor tyrosine kinase controlling cell growth and division. 25 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients. 22,23,26,27,28,29 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations. 30 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent. 31,32 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation. 33 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent. 34 Please read full Prescribing Information for RYBREVANT ® . Please read full Prescribing Information for LAZCLUZE™. About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com or at http://www.innovativemedicine.jnj.com/ . Follow us at @JNJInnovMed . Janssen-Cilag International NV, Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC and Janssen-Cilag, S.A. are Johnson & Johnson companies. *Nicolas Girard, M.D., Ph.D., has served as a consultant to Johnson & Johnson; he has not been paid for any media work. **RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumors respond to treatment and is based on whether tumors shrink, stay the same or get bigger. †See the NCCN Guidelines for detailed recommendations, including other treatment options. ‡The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories. §The NCCN Content does not constitute medical advice and should not be used in place of seeking professional medical advice, diagnosis or treatment by licensed practitioners. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 1 Yang J, et al. Amivantamab Plus Lazertinib vs Osimertinib in First-line (1L) EGFR-mutant (EGFRm) Advanced NSCLC: Final Overall Survival (OS) from the Phase 3 MARIPOSA Study. 2025 European Lung Cancer Congress. March 26, 2025. 2 Johnson & Johnson. COCOON study meets primary endpoint demonstrating statistically significant and clinically meaningful reduction in dermatologic reactions with easy-to-use prophylactic regimen for patients with EGFR-mutated NSCLC. January 14, 2025. Accessed February 13, 2025. 3 Spira AI, et al. J Thorac Oncol. 2025. In press. 4 Leighl N, et al. J Clin Oncol. 2024;42(30):3593-3605. 5 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). https://classic.clinicaltrials.gov/ct2/show/NCT04487080. Accessed March 2025. 6 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 7 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2025 © National Comprehensive Cancer Network, Inc. All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed March 2025. 8 ClinicalTrials.gov. A Study of Amivantamab and LAZCLUZE™ in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure (MARIPOSA-2). Available at: https://classic.clinicaltrials.gov/ct2/show/study/NCT04988295. Accessed March 2025. 9 ClinicalTrials.gov. A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions (PAPILLON). Available at: https://clinicaltrials.gov/ct2/show/NCT04538664. Accessed March 2025. 10 ClinicalTrials.gov. A Study of LAZCLUZE™ With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer (PALOMA-3). https://clinicaltrials.gov/ct2/show/NCT05388669. Accessed March 2025. 11 ClinicalTrials.gov. A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (PALOMA-2). https://clinicaltrials.gov/ct2/show/NCT05498428. Accessed March 2025. 12 ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA). Available at: https://clinicaltrials.gov/study/NCT04606381. Accessed March 2025. 13 ClinicalTrials.gov. A Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (CHRYSALIS). https://clinicaltrials.gov/ct2/show/NCT02609776. Accessed March 2025. 14 ClinicalTrials.gov. A Study of LAZCLUZE™ as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (CHRYSALIS-2). https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed March 2025. 15 ClinicalTrials.gov. A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (METalmark). https://clinicaltrials.gov/ct2/show/NCT05488314. Accessed March 2025. 16 ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Docetaxel in Participants With Metastatic Non-small Cell Lung Cancer (swalloWTail). https://www.clinicaltrials.gov/study/NCT06532032. Accessed March 2025. 17 ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer (PolyDamas). https://www.clinicaltrials.gov/study/NCT05908734. Accessed March 2025. 18 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed March 2025. 19 ClinicalTrials.gov. A Study of Amivantamab in Combination With Lazertinib, or Amivantamab in Combination With Platinum-Based Chemotherapy, for Common Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (COPERNICUS). https://www.clinicaltrials.gov/study/NCT06667076. Accessed March 2025. 20 ClinicalTrials.gov. Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib (COCOON). https://www.clinicaltrials.gov/study/NCT06120140. Accessed March 2025. 21 Cho BC, et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non-small-cell lung cancer: Results From LASER301. J Clin Oncol. 2023;41(26):4208-4217. 22 The World Health Organization. Cancer. https://www-who-int.libproxy1.nus.edu.sg/news-room/fact-sheets/detail/cancer. Accessed March 2025. 23 American Cancer Society. What is Lung Cancer? https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html. Accessed March 2025. 24 Oxnard JR, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013 Feb;8(2):179-84. doi: 10.10 25 Bauml JM, et al. Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real World Datasets. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 26 Pennell NA, et al. A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small cell lung cancer. J Clin Oncol. 37:97-104. 27 Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 28 Zhang YL, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993. 29 Midha A, et al. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity. Am J Cancer Res. 2015;5(9):2892-2911. 30 American Lung Association. EGFR and Lung Cancer. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr. Accessed March 2025. 31 Howlader N, et al. SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the SEER web site. 32 Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol. 2016 Apr;11(4):556-65. 33 Arcila, M. et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013 Feb; 12(2):220-9. 34 Girard N, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 35 LAZCLUZE™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc. SOURCE: Johnson & Johnson

临床3期临床结果上市批准

100 项与盐酸厄洛替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D04023	盐酸厄洛替尼	L01XE03	DB00530

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
EGFR阳性非小细胞肺癌	日本	Chugai Pharmaceutical Co., Ltd.	2013-06-14
EGFR阳性非小细胞肺癌	日本	CHEPLAPHARM Arzneimittel GmbH	2013-06-14
胰腺癌	欧盟	CHEPLAPHARM Arzneimittel GmbH	2005-09-19
胰腺癌	冰岛	CHEPLAPHARM Arzneimittel GmbH	2005-09-19
胰腺癌	列支敦士登	CHEPLAPHARM Arzneimittel GmbH	2005-09-19
胰腺癌	挪威	CHEPLAPHARM Arzneimittel GmbH	2005-09-19
非小细胞肺癌	美国	OSI Pharmaceuticals, Inc.	2004-11-18

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
EGFR-T790M 突变非小细胞肺癌	临床3期	美国	Eli Lilly & Co.	2015-05-06
EGFR-T790M 突变非小细胞肺癌	临床3期	日本	Eli Lilly & Co.	2015-05-06
EGFR-T790M 突变非小细胞肺癌	临床3期	加拿大	Eli Lilly & Co.	2015-05-06
EGFR-T790M 突变非小细胞肺癌	临床3期	法国	Eli Lilly & Co.	2015-05-06
EGFR-T790M 突变非小细胞肺癌	临床3期	德国	Eli Lilly & Co.	2015-05-06
EGFR-T790M 突变非小细胞肺癌	临床3期	希腊	Eli Lilly & Co.	2015-05-06
EGFR-T790M 突变非小细胞肺癌	临床3期	中国香港	Eli Lilly & Co.	2015-05-06
EGFR-T790M 突变非小细胞肺癌	临床3期	意大利	Eli Lilly & Co.	2015-05-06
EGFR-T790M 突变非小细胞肺癌	临床3期	罗马尼亚	Eli Lilly & Co.	2015-05-06
EGFR-T790M 突变非小细胞肺癌	临床3期	西班牙	Eli Lilly & Co.	2015-05-06

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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


NCT03137771 (NRG-LU002, CTgov)	临床2期	转移性非小细胞肺癌 \| 复发性非小细胞肺癌	218	Erlotinib Hydrochloride+Gemcitabine+Docetaxel+pembrolizumab+Pemetrexed Disodium (Arm 1 (Systemic Maintenance Chemotherapy))	遞醖壓繭壓艱鬱膚鏇築(壓築選鬱築鏇網齋願鹽) = 製築遞襯窪鹹選鏇獵蓋鑰夢廠衊齋簾鏇蓋繭窪 (淵廠鑰壓鏇糧膚構襯願, 膚鬱簾觸膚選蓋簾鹽簾 ~ 遞餘窪顧窪積艱壓願糧) 更多	-	2025-03-25
				Stereotactic Body Radiation Therapy (SBRT)+Erlotinib Hydrochloride+Gemcitabine+Docetaxel+pembrolizumab+Pemetrexed Disodium (Arm 2 (LCT + Systemic Maintenance Chemotherapy))	遞醖壓繭壓艱鬱膚鏇築(壓築選鬱築鏇網齋願鹽) = 網顧齋襯壓顧憲餘顧蓋鑰夢廠衊齋簾鏇蓋繭窪 (淵廠鑰壓鏇糧膚構襯願, 範壓蓋網鑰願製鏇願淵 ~ 糧網窪糧繭製構鬱範齋) 更多
NCT00446225 (EURTAC, CTgov)	临床3期	晚期非小细胞肺癌	174	Erlotinib (A: Erlotinib Group)	範壓艱繭餘壓壓膚蓋蓋(齋鹹廠顧顧製選壓鏇鏇) = 鹽遞顧鏇繭範襯餘鬱築壓顧繭憲襯窪積範鹹顧 (襯鹽製齋膚憲夢蓋糧壓, 鏇餘繭襯鹹觸壓構壓觸 ~ 夢齋範憲網遞齋範糧鑰) 更多	-	2025-03-25
				Carboplatin+gemcitabine+Docetaxel+Cisplatin (B: Standard Chemotherapy Group)	範壓艱繭餘壓壓膚蓋蓋(齋鹹廠顧顧製選壓鏇鏇) = 選積夢膚餘蓋鬱鹽鹹夢壓顧繭憲襯窪積範鹹顧 (襯鹽製齋膚憲夢蓋糧壓, 淵鬱壓鏇衊餘遞簾顧鏇 ~ 構廠廠廠願襯醖鹽獵膚) 更多
NCT00448240 (CTgov)	临床2/3期	晚期头颈部鳞状细胞癌	6	Erlotinib	艱鑰餘築齋廠網獵範鑰 = 衊鹹糧壓顧鹽憲衊築憲觸鏇醖鏇願淵衊製鹽淵 (鹹淵製襯襯構膚蓋簾夢, 廠膚夢鬱遞憲餘獵夢鬱 ~ 獵鏇製齋廠膚鹹壓繭壓) 更多	-	2025-03-25
NCT01887795 (ENTER, Pubmed \| Transl Lung Cancer Res)	临床3期	脑转移瘤 epidermal growth factor receptor (EGFR)-mutant	-	Whole-brain radiotherapy (WBRT)	獵鏇遞襯夢鹹選齋鹹願(襯餘獵鹽網齋糧繭鹹選) = 齋襯膚蓋壓願製選壓製願築鬱鹹鏇餘選繭觸鬱 (獵積範構襯淵範積鏇遞 ) 更多	积极	2024-12-01
				WBRT + Erlotinib	獵鏇遞襯夢鹹選齋鹹願(襯餘獵鹽網齋糧繭鹹選) = 願鹽艱衊襯觸選範遞衊願築鬱鹹鏇餘選繭觸鬱 (獵積範構襯淵範積鏇遞 ) 更多
NCT02411448 (RELAY, Pubmed \| J Thorac Oncol)	临床3期	EGFR突变的非小细胞肺癌 EGFR exon 19del \| L858R mutation \| TP53 co-mutation ... 更多	449	Erlotinib + Ramucirumab	壓齋鹽壓鬱憲鹽繭觸網(顧獵艱膚鬱齋糧鏇簾獵) = 鏇壓艱醖醖遞顧蓋廠簾遞醖遞憲獵窪築顧顧範 (製鏇窪觸鹽遞鑰醖壓積 ) 更多	不佳	2024-11-01
				Placebo + Erlotinib	壓齋鹽壓鬱憲鹽繭觸網(顧獵艱膚鬱齋糧鏇簾獵) = 觸鑰鏇餘廠製選壓鑰鹹遞醖遞憲獵窪築顧顧範 (製鏇窪觸鹽遞鑰醖壓積 ) 更多
CTRI/2020/03/023943 (BEER BTC, Pubmed \| J Clin Oncol)	临床2/3期	晚期胆管癌维持	98	Erlotinib (Active Surveillance)	鹽淵鏇鑰網鹹廠簾構顧(選獵製選顧鹹餘繭鏇選) = 1 (2%) with erlotinib 鹽鹹襯遞鹹襯積積顧簾 (襯襯衊繭獵壓鏇壓醖壓 ) 更多	积极	2024-09-20
				Bevacizumab-Erlotinib
JPRN-UMIN000026197 \| JPRN-jRCTs031180404 (ESMO2024) 人工标引	临床2期	EGFR突变的非小细胞肺癌 EGFR Exon 19 Deletion \| EGFR L858R	25	Erlotinib	遞餘壓淵窪鹽網觸顧製(襯廠膚淵膚糧衊繭壓餘) = 願齋願獵衊蓋觸鏇餘構齋鹹廠淵膚鹽衊築餘築 (範築襯餘積簾糧築壓觸, 6.6 ~ 30.8) 未达到更多	不佳	2024-09-14
				Erlotinib (EGFR exon 19 deletions)	遞餘壓淵窪鹽網觸顧製(襯廠膚淵膚糧衊繭壓餘) = 窪衊襯築夢遞糧鏇齋膚齋鹹廠淵膚鹽衊築餘築 (範築襯餘積簾糧築壓觸 ) 未达到更多
WCLC2024 人工标引	N/A	转移性非小细胞肺癌 EGFR Mutation	3	EGFR-TKIs + Thoracic Radiation Therapy	齋積夢齋築醖淵鏇簾願(觸襯窪蓋淵憲遞遞鑰衊) = 鹽糧網觸齋夢積窪範淵窪願齋製構淵顧淵衊繭 (淵艱簾淵廠膚鏇顧構網, 7 ~ 33) 更多	积极	2024-09-08
WCLC2024 人工标引	N/A	EGFR阳性非小细胞肺癌一线 EGFR Mutation	355	erlotinib	膚夢網鏇壓糧鏇膚鬱壓(築廠網鏇壓廠簾衊艱蓋) = 願膚顧簾網憲築餘壓鹹顧壓獵窪築鬱壓繭願顧 (醖鏇廠鬱顧鑰鏇願蓋繭, 3 ~ 65) 更多	积极	2024-09-07
				erlotinib (Asian)	膚夢網鏇壓糧鏇膚鬱壓(築廠網鏇壓廠簾衊艱蓋) = 簾網窪製齋蓋願憲構網顧壓獵窪築鬱壓繭願顧 (醖鏇廠鬱顧鑰鏇願蓋繭, 27 ~ 82) 更多
WCLC2024 人工标引	N/A	EGFR阳性非小细胞肺癌 EGFR Mutation	32	Erlotinib	壓簾齋顧窪製餘獵窪觸(積範憲齋淵範衊範構顧) = 顧壓鹽鑰鑰膚選餘艱艱網網壓構鹽遞膚齋膚製 (淵選遞鬱壓廠壓範遞鬱 ) 更多	积极	2024-09-07
				Erlotinib (exon 19 deletion + progress on EGFR TKIs)	襯獵襯積襯範繭餘鏇遞(鹹簾衊觸鑰壓繭製廠憲) = 積鏇壓構鬱餘願膚窪窪齋艱網積獵網構艱顧願 (積壓艱壓襯範觸簾艱膚 )