J2J-MC-JZLH EMBER-4: A Randomized, Open-Label, Phase 3 Study of Adjuvant Imlunestrant vs Standard Adjuvant Endocrine Therapy in Patients who have Previously Received 2 to 5 years of Adjuvant Endocrine Therapy for ER+, HER2- Early Breast Cancer with an Increased Risk of Recurrence - 18459

开始日期2023-04-27

申办/合作机构

Eli Lilly & Co.

NCT05509790

/ Active, not recruiting临床1期

A Phase 1 Study of LY3484356 in Chinese Patients With Estrogen Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer

This is a study of LY3484356 in Chinese participants with advanced breast cancer. Participants must have breast cancer that is estrogen receptor positive (ER+), HER2 negative (HER2-). The purpose of this study is to measure how much LY3484356 gets into the bloodstream and how long it takes the body to remove it. The safety and effectiveness of LY3484356 will also be studied. Participation could last up to 28 months.

开始日期2022-10-09

申办/合作机构

Eli Lilly & Co.

100 项与 Imlunestrant 相关的临床结果

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100 项与 Imlunestrant 相关的转化医学

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100 项与 Imlunestrant 相关的专利（医药）

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项与 Imlunestrant 相关的文献（医药）

2025-03-27·NEW ENGLAND JOURNAL OF MEDICINE

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer

Article

作者: Jhaveri, Komal L. ; Pradhan, Kamnesh R. ; Lim, Elgene ; Sohn, Joohyuk ; Llombart-Cussac, Antonio ; Saura, Cristina ; Mattar, André ; Ruíz Borrego, Manuel ; Harbeck, Nadia ; Wang, Xuejing Aimee ; Cramer von Laue, Christoph ; Barrett, Emily ; Carey, Lisa A. ; O’Shaughnessy, Joyce ; Neven, Patrick ; Nakamura, Rikiya ; Martinez Rodriguez, Jorge Luis ; Tokunaga, Eriko ; Kim, Sung-Bae ; Cao, Shanshan ; Huang, Chiun-Sheng ; Bidard, François-Clément ; Zhang, Qingyuan ; Smyth, Lillian M. ; Casalnuovo, Monica Lis ; Hung, Chih-Chiang ; Curigliano, Giuseppe ; García Tinoco, María de la Luz ; Aftimos, Philippe

BACKGROUND:

Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα (ESR1).

METHODS:

In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib. Primary end points were investigator-assessed progression-free survival with imlunestrant as compared with standard therapy among patients with ESR1 mutations and among all patients and with imlunestrant-abemaciclib as compared with imlunestrant among all patients who had undergone randomization concurrently.

RESULTS:

Overall, 874 patients underwent randomization, with 331 assigned to imlunestrant, 330 to standard therapy, and 213 to imlunestrant-abemaciclib. Among 256 patients with ESR1 mutations, the median progression-free survival was 5.5 months with imlunestrant and 3.8 months with standard therapy. The estimated restricted mean survival time at 19.4 months was 7.9 months (95% confidence interval [CI], 6.8 to 9.1) with imlunestrant and 5.4 months (95% CI, 4.6 to 6.2) with standard therapy (difference, 2.6 months; 95% CI, 1.2 to 3.9; P<0.001). In the overall population, the median progression-free survival was 5.6 months with imlunestrant and 5.5 months with standard therapy (hazard ratio for progression or death, 0.87; 95% CI, 0.72 to 1.04; P = 0.12). Among 426 patients in the comparison of imlunestrant-abemaciclib with imlunestrant, the median progression-free survival was 9.4 months and 5.5 months, respectively (hazard ratio, 0.57; 95% CI, 0.44 to 0.73; P<0.001). The incidence of grade 3 or higher adverse events was 17.1% with imlunestrant, 20.7% with standard therapy, and 48.6% with imlunestrant-abemaciclib.

CONCLUSIONS:

Among patients with ER-positive, HER2-negative advanced breast cancer, treatment with imlunestrant led to significantly longer progression-free survival than standard therapy among those with ESR1 mutations but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival as compared with imlunestrant, regardless of ESR1-mutation status. (Funded by Eli Lilly; EMBER-3 ClinicalTrials.gov number, NCT04975308.).

2025-03-01·Nature Reviews Clinical Oncology

Imlunestrant shows efficacy both with and without abemaciclib

Article

作者: Killock, David

2025-02-17·CANCER RESEARCH

Imlunestrant Is an Oral, Brain-Penetrant Selective Estrogen Receptor Degrader with Potent Antitumor Activity in ESR1 Wild-Type and Mutant Breast Cancer

Article

作者: Shen, Weihua ; Kindler, Lisa ; de Dios, Alfonso ; Garcia-Tapia, David ; Dowless, Michele S. ; Ortiz Ruiz, Maria Jesus ; Bastian, Jolie ; Rodrik-Outmezguine, Vanessa ; Rodriguez Cruz, Vivian ; Yu, Chunping ; Castanares, Mark A. ; Klippel, Anke ; Bhagwat, Shripad V. ; Marugán, Carlos ; Mattioni, Brian ; Fei, Dongling ; Vandekopple, Matthew ; Cohen, Jeff D. ; Ismail-Khan, Roohi ; Gong, Xueqian ; Stephens, Jennifer R. ; Peng, Sheng-Bin ; Capen, Andrew ; Bacchion, Francesca ; Puca, Loredana ; Zhao, Baohui ; Lallena, María Jose ; Yuen, Eunice ; Manro, Jason R. ; Baker, Thomas K. ; Pulliam, Nicholas ; Mur, Cecilia ; Huber, Lysiane

Abstract:

Targeting of the estrogen receptor (ER) by antiestrogens is the standard of care for patients with ER+ HER2− advanced/metastatic breast cancer. Although antiestrogens that degrade ERα (fulvestrant) or block estrogen production (aromatase inhibitors) have improved patient outcomes, clinically important challenges remain related to drug administration, limited bioavailability, lack of brain exposure, and acquired resistance due to ESR1 mutations. These limitations indicate a need for more robust ER-targeted therapies. Here, we discovered and characterized imlunestrant, a next-generation potent, brain-penetrant oral selective ER degrader. Imlunestrant degraded ERα and decreased ERα-mediated gene expression both in vitro and in vivo. Cell proliferation and tumor growth in ESR1 wild-type (WT) and mutant models were significantly inhibited by imlunestrant. Combining imlunestrant with abemaciclib (CDK4/6 inhibitor), alpelisib (PI3K inhibitor), or everolimus (mTOR inhibitor) further enhanced tumor growth inhibition, regardless of ESR1 mutational status. In an ER+ breast cancer intracranial tumor model, imlunestrant prolonged survival compared with vehicle or alternative selective ER degrader therapies. Together, these findings support the potential of imlunestrant to degrade ERα and suppress the growth of ESR1-WT and mutant breast cancer, including brain metastatic tumors.Significance: Imlunestrant, a next-generation, brain-penetrant oral ERα degrader, displays potent activity in ESR1 wild-type and mutant breast cancer, enhances combination activity with standard-of-care agents, and inhibits growth of ER+ intracranial tumors.

项与 Imlunestrant 相关的新闻（医药）

2025-06-13

·ioncology

ASCO国际视野丨Giuseppe Curigliano教授：EMBER-3研究PRO分析揭示HR+/HER2-乳腺癌治疗新视角

编者按：2025年美国临床肿瘤学会（ASCO）年会上，ESMO候任主席、意大利米兰欧洲肿瘤研究所（IEO）Giuseppe Curigliano教授分享了III期EMBER-3研究中患者报告结局（PRO）分析结果，揭示了imlunestrant单药或imlunestrant+阿贝西利在HR+/HER2-晚期乳腺癌患者治疗中整体健康状况/生活质量及身体功能评分。肿瘤瞭望在会上特邀采访了Giuseppe Curigliano教授，请其分享了imlunestrant单药与imlunestrant+阿贝西利联合治疗的临床适用性、患者生活质量改善情况，以期为临床实践提供新视角。研究简介Patient-reported outcomes (PROs) in patients with ER+, HER2- advanced breast cancer (ABC) treated with imlunestrant, investigator’s choice standard endocrine therapy, or imlunestrant + abemaciclib: Results from the phase III EMBER-3 trial.Imlunestrant单药或联合阿贝西利治疗ER+/HER2-晚期乳腺癌患者：EMBER-3 III期试验患者报告结局（PRO）研究背景imlunestrant（imlu）是一种新一代、可穿透血脑屏障的口服选择性雌激素受体降解剂。在针对接受基于芳香化酶抑制剂治疗后疾病进展的ER阳性/HER2阴性晚期乳腺癌（ABC）患者的EMBER-3研究中，结果显示，在ESR1突变（ESR1m）患者中，与标准疗法（SOC，包括氟维司群或依西美坦）相比，使用imlunestrant可显著延长无进展生存期（PFS）；而在所有患者中，无论是否存在ESR1m，与imlunestrant单药治疗相比，imlunestrant+abemaciclib（imlu+abema）联合治疗均显示出更好的疗效。本文呈现探索性患者报告结局（PRO）分析结果。研究方法在基线（BL）时以及每8周直至治疗结束时，使用欧洲癌症研究与治疗组织（EORTC）QLQ-C30 核心问卷进行评估。预先指定的QLQ-C30分析采用纵向混合模型对重复测量数据进行处理，以计算基线与基线后至少一次得分之间的平均变化。每周对患者进行PRO-CTCAE（腹泻频率）评估，报告范围为0（从未）到4（几乎持续存在）。对接受氟维司群治疗的患者，在注射后两周内每周进行PRO-CTCAE（注射部位反应[ISR]）评估，报告是否出现疼痛、肿胀、发红等症状。采用描述性分析方法对PRO-CTCAE进行分析。研究结果在存在ESR1突变的患者中，与标准治疗相比，imlunestrant单药治疗与EORTC QLQ-C30多个评分的改善或维持相关，而标准治疗组的评分则有所下降或维持不变。具体而言，接受imlunestrant治疗的ESR1突变患者，其整体健康状况（GHS）/生活质量（QOL）和身体功能（PF）评分有所改善，而标准治疗组评分则下降（治疗组间平均变化差异分别为9.9 [0.1, 19.7]和6.2 [-0.8, 13.1]）。这些患者报告结局（PRO）发现与该组患者的无进展生存期（PFS）结果相吻合。在总体人群中，imlunestrant组与标准治疗组在整体健康状况/生活质量评分方面下降幅度相似（平均变化差异：0.5 [-4.7, 5.7]），身体功能评分在imlunestrant组保持稳定，而标准治疗组略有下降（平均变化差异：2.5 [-1.1, 6.1]）。大多数接受氟维司群治疗的患者（72%）在治疗期间报告了注射部位反应（ISR），前6个治疗周期的第一周平均发生率为31%。imlunestrant联合阿贝西利组与imlunestrant单药组相比，所有患者的整体健康状况/生活质量评分和身体功能评分下降幅度相似（整体健康状况/生活质量评分平均变化差异：0.8 [-7.4, 5.9]；身体功能评分平均变化差异：-2.2 [-6.6, 2.2]）。患者报告的“频繁”或“几乎持续”腹泻发生率在imlunestrant组（3%）和标准疗法组（2%）相似，而imlunestrant联合阿贝西利组发生率较高（22%）。研究结论EMBER-3研究的患者报告结局显示，在存在ESR1突变的患者中，与标准治疗相比，imlunestrant单药治疗可改善患者的整体健康状况/生活质量及身体功能评分，这与疗效结果相吻合。尽管根据CTCAE定义的注射部位反应发生率较低，但PRO-CTCAE评估显示注射部位反应的发生率较高，这表明这一具有临床相关性的不良事件可能被医生低估了。总体而言，这些结果支持imlunestrant相较于现有标准治疗的有效性和安全性。研究者说01《肿瘤瞭望》：请您为我们介绍下，在您报告的EMBER-3研究中都使用了哪些患者报告结局（PROs）评估工具？如何确保PROs数据的准确性和可靠性？Giuseppe Curigliano 教授意大利米兰欧洲肿瘤研究所（IEO）EMBER-3是一项前瞻性、随机对照研究，比较了Imlunestrant单药与标准内分泌治疗方案（SOC）的疗效，以及Imlunestrant单药与Imlunestrant联合阿贝西利（abemaciclib）的疗效。在本研究中，研究团队将患者报告结局（PROs）、整体健康状况及生活质量作为次要终点进行评估。结果显示，在生活质量方面，Imlunestrant单药与标准治疗的比较中，Imlunestrant单药在各项功能状态指标上均表现出数值提升；在Imlunestrant单药与联合阿贝西利的比较中也观察到类似结果。因此，在患者整体健康状况和生活质量方面，Imlunestrant单药治疗方案展现出更优的患者报告结局。值得一提的是，研究中仅有一个变量存在显著差异，即腹泻的发生率。此外，对于接受氟维司群治疗的患者而言，注射部位反应是多数患者在研究过程中报告的主要不适之一。基于这些数据，研究认为，Imlunestrant联合阿贝西利可作为HR+/HER2-人群的一种新的治疗选择；而对于携带ESR1突变的患者，Imlunestrant单药也为其提供了新的治疗可能。上下滑动查看英文采访内容Could you please share with us which Patient-Reported Outcomes (PROs) assessment tools were utilized in the EMBER-3 study you presented? How was the accuracy and reliability of the PROs data ensured?EMBER-3 was a prospective randomized trial comparing Imlunestrant alone to standard of care in endocrine therapy and Imlunestrant alone versus Imlunestrant plus abemaciclib. In EMBER-3, as a secondary endpoint, we evaluated patient-reported outcomes, global health status and quality of life. What we discovered is that when comparing A versus B, Imlunestrant versus standard of care, quality of life was numerically improved in all the variables of functional status. Similar results have been obtained when comparing Imlunestrant alone to Imlunestrant plus abemaciclib. So, when evaluating global health status and quality of life in our patients, we have a better outcome, a better patient-reported outcome.Only in one variable there was a difference, that was the incidence of diarrhea. Importantly, injection site reaction of fulvestrant was the main complaint for the majority of the patients that had been enrolled in EMBER-3. So, according to this data, we confirm Imlunestrant plus abemaciclib in all population and Imlunestrant alone in ESR1-mutant patients, is a new option for patients with HR-positive/HER2-negative disease.02《肿瘤瞭望》：Imlunestrant与abemaciclib的联合治疗在EMBER-3研究中显示出了一定的疗效，但患者报告的生活质量并未显著优于单药治疗。您认为这种组合策略在未来临床实践中的适用范围和潜在挑战是什么？是否有特定的患者群体更适合这种联合治疗方案？Giuseppe Curigliano 教授意大利米兰欧洲肿瘤研究所（IEO）我认为，这项研究最重要的意义在于，它为HR+/HER2-乳腺癌患者提供了一种全口服联合治疗的新选择，无论患者有没有接受过CDK4/6抑制剂治疗，或是在治疗后出现疾病进展。我个人认为，这一方案在临床实践中并不存在显著挑战，相反，它为患者带来了在治疗便利性与依从性方面的全新机遇。上下滑动查看英文采访内容The combination therapy of imlunestrant and abemaciclib demonstrated certain efficacy in the EMBER-3 study, yet patient-reported quality of life did not significantly surpass that of monotherapy. What do you believe are the applicable scenarios and potential challenges for this combination strategy in future clinical practice? Are there specific patient populations that might be more suitable for this combination treatment regimen?I believe the most important information from this study is the opportunity to offer an all oral combination in patients with HR-positive/HER2-negative disease, both those who received the CDK4/6 inhibitors or those who progressed to CDK4/6 inhibitors. I don't see major challenges. I see only an opportunity to offer the patients an all oral combination.03《肿瘤瞭望》：尽管CTCAE定义的注射部位反应（ISR）发生率较低，但PRO-CTCAE结果显示ISR是一个被低估的临床相关不良事件。您认为医生在临床实践中应如何更准确地识别和管理这类被低估的不良事件，以提高患者的治疗体验和依从性？Giuseppe Curigliano 教授意大利米兰欧洲肿瘤研究所（IEO）众所周知，口服用药显然比肌肉注射更为方便。如果患者需要每28天接受一次肌肉注射，这不仅会增加治疗过程中的不便，同时也可能带来不良反应。因此，我个人认为，在临床实践中，能够提供口服药物，无论是在治疗还是生活质量方面，对患者来说都是有利的机会。上下滑动查看英文采访内容Despite the relatively low incidence of injection site reactions (ISR) as defined by the Common Terminology Criteria for Adverse Events (CTCAE), PRO-CTCAE findings suggest that ISR are an underrecognized clinically relevant adverse event. How do you believe clinicians should more accurately identify and manage such underrecognized adverse events in clinical practice to improve patients' treatment experience and adherence?More dramatically, it's easier to take an oral pill rather than doing an intramuscular injection. Of course, if you have a patient that should receive every 28 days an intramuscular injection, this is a logistical problem and at the same time can also be an adverse event. So, personally, I believe in clinical practice that having an oral option for my patients, it's a huge opportunity for our patients, both in terms of logistics and in terms of quality. Giuseppe Curigliano 教授医学博士欧洲肿瘤内科学会（ESMO）候任主席意大利米兰欧洲肿瘤研究所（IEO）早期药物开发部主任实验治疗项目联合主席米兰大学肿瘤与血液肿瘤科学系指导委员会成员意大利国家卫生理事会成员《ESMO Open》主编《欧洲肿瘤学杂志》（European Journal of Oncology）《临床肿瘤学杂志》（Journal of Clinical Oncology）《肿瘤学年鉴》（Annals of Oncology）等国际期刊编委（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。

临床结果ASCO会议临床3期

2025-06-08

·药事纵横

全球首款PROTAC药物申报FDA，靶向降解攻克乳腺癌耐药难题

6月6日，Arvinas与辉瑞联合宣布，已向美国FDA提交其PROTAC分子vepdegestrant（ARV-471）的新药上市申请（NDA）。这个申请针对的是既往接受过内分泌药物治疗的携带ESR1突变的ER阳性/HER2阴性晚期或转移性乳腺癌患者。若获批，vepdegestrant将成为全球首个上市的PROTAC药物。Vepdegestrant的上市申请主要基于一项名为VERITAC-2的III期临床试验结果。这项多中心、随机、开放标签研究纳入了624名曾经接受过CDK4/6抑制剂和内分泌治疗的ER阳性/HER2阴性晚期乳腺癌患者。研究结果显示，在携带ESR1突变的患者群体中，vepdegestrant展现出了突破性疗效。相比对照组药物氟维司群，vepdegestrant将患者的中位无进展生存期（PFS）从2.1个月显著延长至5.0个月，疾病进展或死亡风险降低43%（HR=0.57；95% CI：0.42–0.77，P<0.001）。在全部人群中，虽然vepdegestrant组和氟维司群组的PFS未达到统计学显著差异（3.7个月 vs 3.6个月，HR=0.83），但ESR1突变亚组的突出获益足以支撑其成为该人群的重要治疗选择。安全性方面，vepdegestrant表现出可接受的安全性特征。两组3级及以上治疗期间不良事件（TEAE）发生率分别为23.4%和17.6%。最常见的TEAE包括疲劳（26.6% vs 15.6%）、ALT升高（14.4% vs 9.8%）、AST升高（14.4% vs 10.4%）和恶心（13.5% vs 8.8%）。那么，PROTAC技术到底有何特别之处？为何能引起行业如此大的关注？与传统药物不同，PROTAC分子是双功能小分子，一端结合目标蛋白，另一端结合E3连接酶。这种设计能巧妙地将目标蛋白“拉”到E3连接酶附近，给目标蛋白打上泛素标签，标记它们送入细胞的蛋白酶体系统进行降解。这相当于给癌细胞内部的“垃圾处理系统”贴上了明确的清除标签，而非仅仅阻断其功能。传统抑制剂需要持续占据靶蛋白的活性位点才能发挥作用，而PROTAC分子只需短暂结合即可完成“标记”任务，随后可循环利用，理论上具有更高的效率。在临床实践中，vepdegestrant在200mg推荐剂量下实现了69%的ER降解率，为PROTAC的作用机制提供了临床概念验证。临床前研究更显示，它在肿瘤细胞中ER降解率高达97%，显著优于传统口服SERD类药物。回顾PROTAC技术的发展史，要追溯到2001年耶鲁大学的Craig Crews教授与其合作伙伴发表的一篇论文，当时，研究人员设计了一种人造双功能分子，将其命名为蛋白靶向嵌合分子-1（Protac-1）。2008年，Crews教授团队更进一步，开发出第一个双功能小分子PROTAC药物，能够靶向降解雄激素受体，这个分子被正式命名为“PROTAC”（PROteolysis TArgeting Chimera），成为整个领域的命名来源。2013年，Crews教授联合创办了Arvinas公司，开始加速推进这一技术的科学转化。公司明智地选择从雄激素受体和雌激素受体这两个相对成熟的靶点切入，其中靶向雌激素受体的项目就是今天的vepdegestrant。2021年，辉瑞看到了vepdegestrant的潜力，与Arvinas达成了超20亿美元的合作协议，共同推进这款药物的开发，将其定位为治疗ER阳性乳腺癌患者的支柱性内分泌疗法。在vepdegestrant领跑的同时，整个靶向蛋白降解领域呈现百花齐放的繁荣景象。Arvinas自身还有多个PROTAC项目在推进中，包括与诺华就其针对雄激素受体的第二代PROTAC降解剂ARV-766达成了超过10亿美元的合作。目前，Arvinas针对LRRK2的蛋白降解剂ARV-102，已进入1期临床试验，旨在治疗帕金森病。初步分析显示，该药物能够实现中枢神经系统及外周LRRK2蛋白的显著降解，为神经退行性疾病治疗开辟了新途径。其他公司也在开发类似机制的创新药物。Kymera Therapeutics公司和赛诺菲联合开发的IRAK4靶向蛋白降解剂KT-474（SAR444656）已处于临床阶段，用于治疗化脓性汗腺炎和特应性皮炎。Nurix Therapeutics公司专注于可穿越血脑屏障的布鲁顿氏酪氨酸激酶（BTK）蛋白降解剂NX-5948，目前处于1b/2期临床开发阶段。在治疗复发/难治性华氏巨球蛋白血症患者时，该药物达到77.8%的客观缓解率。在PROTAC之外，多种创新蛋白降解模式也不断涌现。分子胶蛋白降解剂领域近两年来得到多家大型药企的关注，诺华、百健、艾伯维、武田、卫材与诺和诺德等公司纷纷达成分子胶相关的研发合作。一批专注于蛋白降解的新锐公司正在拓展创新边界。Pinetree Therapeutics开发多特异性靶向蛋白质降解剂；Draupnir Bio和Booster Therapeutics基于溶酶体机制开发蛋白降解剂；Firefly Bio由诺贝尔化学奖得主Carolyn Bertozzi教授联合创立，开发蛋白降解剂-抗体偶联药物（DAC）。从商业角度看，乳腺癌是肿瘤领域最大的治疗市场之一。在ER靶向药类别中，在vepdegestrant和口服SERD药物camizestrant上市的推动下，新一代药物预计将在2033年合计获得31亿美元的销售额。其他可能在未来几年获得批准的新药包括口服SERD药物imlunestrant、口服SERM药物lasofoxifene，以及完全ER拮抗剂palazestrant。Vepdegestrant预计将在2025年在欧盟、日本和美国获批上市，2027年进入中国大陆市场，在G7市场，2030年预期销售额达11.9亿美元。从未来应用场景看，vepdegestrant有望作为一种单药治疗药物首次获批上市，用于对内分泌治疗敏感的HR阳性/HER2阴性转移性乳腺癌患者。在HR阳性/HER2阴性的一线转移性治疗中，vepdegestrant与IBRANCE（palbociclib）的联合用药方案也有望获批用于非生物标志物限制人群。Vepdegestrant的上市申请标志着靶向蛋白降解技术从概念走向临床的重要转折点。对于ER阳性/HER2阴性晚期乳腺癌患者，特别是携带ESR1突变的群体，这代表着新的希望。PROTAC技术的魅力则在于它突破了传统药物设计的限制，为“不可成药”靶点提供了新思路。信息来源：[1]https://ir.arvinas.com/news-releases/news-release-details/arvinas-announces-submission-new-drug-application-us-fda[2]https://www.ebiotrade.com/newsf/2025-6/20250602072717303.htm[3]PROTAC Estrogen Receptor Degraders for ER+ Advanced Breast CancerTargeted Oncology. (2025).药事纵横投稿须知：稿费已上调，欢迎投稿

蛋白降解靶向嵌合体临床结果临床3期突破性疗法

2025-06-02

·FierceBiotech

ASCO: AstraZeneca\'s oral SERD tied to 56% PFS benefit in phase 3 breast cancer trial

AstraZeneca reaffirmed that data on the key secondary endpoints of overall survival or time to second disease progression had been immature at the time of the interim analysis\n AstraZeneca has produced some fresh data to back up its blockbuster ambitions for camizestrant, tying the oral SERD to a 56% improvement in progression-free survival (PFS) in a phase 3 breast cancer study.The Serena-6 study had a novel design that reflected an unmet need in individuals with HR-positive, HER2-negative advanced breast cancer. All 315 patients received an aromatase inhibitor and a CDK4/6 inhibitor—either Eli Lilly’s Verzenio, Novartis’ Kisqali or Pfizer’s Ibrance—as their first-line treatment.Physicians then monitored circulating tumor DNA to spot ESR1 mutations. If a mutation was found before disease progression, patients switched to camizestrant and stayed on the CDK4/6 drug.AstraZeneca revealed back in February that, based on an interim readout, the trial had hit its primary endpoint of PFS but saved the detailed data for the American Society of Clinical Oncology (ASCO) meeting in Chicago on Sunday. Specifically, patients who were moved up to camizestrant and a CDK4/6 inhibitor had a median PFS of 16 months, compared to 9.2 months for those who only received the first-line treatment of an aromatase inhibitor and a CDK4/6 inhibitor.As with the previous announcement in February, AstraZeneca reaffirmed that data on the key secondary endpoints of overall survival or time to second disease progression (PFS2) had been immature at the time of the interim analysis. All the drugmaker had to add yesterday was that “a trend toward extended treatment benefit” has so far been observed when it came to PFS2.The company instead wanted to focus on an exploratory endpoint of “time to deterioration in quality of life.” Here, AstraZeneca could point to a 47% reduction in deterioration of global health status and quality of life among the camizestrant cohort—with a median time of 23 months before these patients saw their health status deteriorate compared to 6.4 months for other patients.“As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumour DNA to detect emerging resistance and change therapy at the earliest opportunity; SERENA-6 is redefining the clinical paradigm in breast cancer,” Susan Galbraith, Ph.D., executive vice president of oncology R&D at AstraZeneca, said in a June 1 release. “Camizestrant is the first and only next-generation oral SERD and complete estrogen receptor antagonist to demonstrate benefit in combination with widely approved CDK4/6 inhibitors in this first-line setting, and these results support its potential as a new standard-of-care endocrine therapy backbone in the treatment of HR-positive breast cancer,” Galbraith added.When it came to safety, 60% of patients receiving camizestrant experienced adverse events of grade 3 or higher, compared to 40% of the comparator cohort. But AstraZeneca argued this was “consistent with the longer duration of exposure to the combination of camizestrant and CDK4/6 inhibitors in the trial.”The majority of these side effects were hematological events typically associated with CDK4/6 inhibitor treatment and included neutropenia and leukopenia—abnormally low concentration of a type of white blood cell—and anemia.The PFS endpoint is the first of a series of milestones for the program. AstraZeneca is running another trial in a broader first-line population and two adjuvant studies. Through the program, the company is aiming to establish camizestrant as a new backbone therapy and hit a peak sales target that AstraZeneca CEO Pascal Soriot has set at more than $5 billion.But AstraZeneca could face competition. Lilly reported phase 3 data on its oral SERD imlunestrant in patients who progressed on an aromatase inhibitor late last year. Roche is aiming to have data on giredestrant, its challenger for the market, sometime from mid-2025 onward. AstraZeneca sees the safety profile of its candidate and ability to combine it with a range of other drugs as differentiators.

$ASCO: AstraZeneca\'s oral SERD tied to 56% PFS benefit in phase 3 breast cancer trial$

临床3期临床结果ASCO会议

100 项与 Imlunestrant 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
ER阳性/HER2阴性乳腺癌	申请上市	加拿大	Eli Lilly & Co.	2025-02-01
肝损伤	临床1期	美国	Eli Lilly & Co.	2022-07-05
晚期乳腺癌	临床1期	美国	Eli Lilly & Co.	2019-12-10
晚期乳腺癌	临床1期	日本	Eli Lilly & Co.	2019-12-10
晚期乳腺癌	临床1期	澳大利亚	Eli Lilly & Co.	2019-12-10
晚期乳腺癌	临床1期	比利时	Eli Lilly & Co.	2019-12-10
晚期乳腺癌	临床1期	法国	Eli Lilly & Co.	2019-12-10
晚期乳腺癌	临床1期	西班牙	Eli Lilly & Co.	2019-12-10
晚期乳腺癌	临床1期	中国台湾	Eli Lilly & Co.	2019-12-10
子宫内膜样腺癌	临床1期	美国	Eli Lilly & Co.	2019-12-10

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临床结果

适应症

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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


NCT04975308 (EMBER-3, ASCO2025)	临床3期	晚期乳腺癌	859	Imlunestrant 400 mg QD	餘鏇憲觸選製廠鏇製壓(鹽觸鬱繭艱鑰觸淵衊顧) = 1/0 and 2/0 餘鹽範夢齋觸壓遞觸鑰 (簾夢鏇膚顧鏇襯膚憲壓 ) 更多	积极	2025-05-30
				Standard therapy (fulvestrant or exemestane)
NCT04975308 (EMBER-3, ESMO_BC2025)	临床3期	晚期乳腺癌 ESR1	874	Imlunestrant 400 mg once daily	夢遞鏇膚繭鹹餘範鏇衊(餘遞製選壓選衊顧餘膚) = 製簾憲壓簾繭積襯繭鑰鹽簾築醖淵範糧網鑰顧 (鹽醖鏇範醖繭憲夢窪鹹, 3.8)	积极	2025-05-14
				Standard therapy (fulvestrant or exemestane)	-
NCT04975308 (EMBER-3, ESMO_BC2025)	临床3期	晚期乳腺癌一线 \| 二线 ESR1	-	Imlunestrant 400mg once daily	鹹積鬱糧積觸繭淵蓋顧(餘網夢網鬱鑰製觸願艱) = 廠壓艱範廠構築願壓襯衊鹹遞鏇鏇簾製醖願蓋 (構繭願簾襯鏇鏇築齋製, 4.7 ~ 11.1)	积极	2025-05-14
				Fulvestrant or exemestane per label	鹹積鬱糧積觸繭淵蓋顧(餘網夢網鬱鑰製觸願艱) = 築獵鬱艱簾鏇選糧鏇簾衊鹹遞鏇鏇簾製醖願蓋 (構繭願簾襯鏇鏇築齋製, 2.0 ~ 7.3)
NCT04975308 (EMBER-3, ESMO_BC2025)	临床3期	晚期乳腺癌 PI3K-pathway mutations	874	Imlunestrant	餘廠壓膚築選齋醖窪製(獵夢網醖糧蓋襯願觸鬱) = 膚膚網鑰鹹積繭淵獵鹽糧膚餘鹹範製衊鬱廠壓 (鹽構醖鹹構網簾膚構襯 )	积极	2025-05-14
				Imlunestrant + Abemaciclib	餘廠壓膚築選齋醖窪製(獵夢網醖糧蓋襯願觸鬱) = 窪範艱築觸願夢憲憲選糧膚餘鹹範製衊鬱廠壓 (鹽構醖鹹構網簾膚構襯, 3.7)
NCT05509790 (Phase 1 study, AACR2025)	临床1期	ER阳性/HER2阴性乳腺癌 ER positive	17	Imlunestrant 400 mg	構壓構夢齋網蓋觸繭觸(艱願顧餘艱觸餘願顧遞) = reported by ≥ 2 patients in the imlunestrant 200 mg cohort 蓋憲製膚窪製夢網鹹齋 (齋艱壓壓襯鬱鹹獵選鏇 ) 更多	积极	2025-04-28
				Imlunestrant 200 mg
NCT04975308 (EMBER-3, Pubmed \| N Engl J Med)	临床3期	晚期乳腺癌	874	Imlunestrant	網襯鹽鹹觸鑰襯膚艱鹽(鑰淵簾範夢網鹹鹹鹽醖) = 窪選膚顧鬱齋築鑰夢構窪淵積衊願鏇鹹選製範 (蓋鬱醖襯齋淵顧鏇蓋壓 ) 更多	积极	2025-03-27
				Standard Therapy	網襯鹽鹹觸鑰襯膚艱鹽(鑰淵簾範夢網鹹鹹鹽醖) = 鏇艱夢構構願齋製廠窪窪淵積衊願鏇鹹選製範 (蓋鬱醖襯齋淵顧鏇蓋壓 ) 更多
NCT04975308 (EMBER-3, Pubmed \| SABCS2024) 人工标引	临床3期	晚期乳腺癌	874	Imlunestrant	築獵淵簾膚繭製顧艱築(齋醖鬱齋齋鏇膚憲鹹糧) = 獵淵憲廠襯齋網構餘膚選遞淵糧齋遞鏇鏇鹽鏇 (膚鬱鹹繭襯艱夢壓願顧 ) 更多	积极	2024-12-11
				Standard therapy	築獵淵簾膚繭製顧艱築(齋醖鬱齋齋鏇膚憲鹹糧) = 鬱衊鏇壓鏇窪壓構窪齋選遞淵糧齋遞鏇鏇鹽鏇 (膚鬱鹹繭襯艱夢壓願顧 ) 更多
NCT04188548 (EMBER, Pubmed \| J Clin Oncol) 人工标引	临床1期	ER阳性/HER2阴性乳腺癌 HER2 Negative \| Estrogen receptor	262	Imlunestrant monotherapy	獵顧觸鹽製艱鏇餘構衊(構憲憲網鑰顧鹹艱獵廠) = 窪襯繭夢觸製夢衊襯膚構糧簾網選壓窪襯膚艱 (築積壓遞鹹構顧壓壓築 ) 更多	积极	2024-09-06
				Imlunestrant + abemaciclib	構鬱膚醖淵顧願範糧衊(齋衊築壓憲衊製獵窪窪) = 鏇艱鏇鑰鑰衊壓壓廠鑰廠鬱網網夢醖鹽艱衊廠 (鑰衊廠憲壓糧蓋壓顧襯, 13.8 ~ NA)
NCT04188548 (EMBER, ASCO2024) 人工标引	临床1期	ER阳性/HER2阳性乳腺癌 HER2 Positive	45	Imlunestrant + Trastuzumab	鹽壓選糧襯夢選膚鹹遞(艱鑰鏇網醖蓋遞憲觸願) = 鬱積願簾鑰選廠夢鹽鹹網淵構艱壓壓糧積壓繭 (構膚鑰鬱構網夢繭繭鬱 ) 更多	积极	2024-05-24
				Imlunestrant + Trastuzumab + Abemaciclib	鹽壓選糧襯夢選膚鹹遞(艱鑰鏇網醖蓋遞憲觸願) = 鹹鏇鏇選衊築選顧醖壓網淵構艱壓壓糧積壓繭 (構膚鑰鬱構網夢繭繭鬱 ) 更多
NCT04188548 (EMBER, ASCO2024) 人工标引	临床1期	子宫内膜癌 ER+	72	Imlunestrant 400mg po daily	鹽衊餘鏇窪鬱繭艱繭淵(襯淵襯鑰襯淵製選憲製) = 遞醖網壓鹽糧鬱醖壓顧齋獵醖構糧選構選襯觸 (齋鹹鑰壓鏇願窪蓋鑰鏇 ) 更多	积极	2024-05-24
				Imlunestrant 400mg po daily + Abemaciclib 150mg po twice daily	鹽衊餘鏇窪鬱繭艱繭淵(襯淵襯鑰襯淵製選憲製) = 廠齋築窪製願餘顧構鏇齋獵醖構糧選構選襯觸 (齋鹹鑰壓鏇願窪蓋鑰鏇 ) 更多