Study Objectives:
Primary
° To evaluate the safety and tolerability of multiple vaginal doses of AZU-101 at 3 dose levels in postmenopausal women
Secondary
* To assess systemic pharmacokinetics (PK) of AZU-101
* To assess the efficacy of multiple vaginal doses of AZU-101 at 3 dose levels in postmenopausal women

开始日期2024-05-01

申办/合作机构

Azure Biotech, Inc.

100 项与 Lasofoxifene Tartrate 相关的临床结果

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100 项与 Lasofoxifene Tartrate 相关的转化医学

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100 项与 Lasofoxifene Tartrate 相关的专利（医药）

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269

项与 Lasofoxifene Tartrate 相关的文献（医药）

2025-06-16·JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

PARP-1 as a novel target in endocrine-resistant breast cancer.

Article

作者: Lappano, Rosamaria ; Zicarelli, Azzurra ; Lainé, Muriel ; Talia, Marianna ; Maggiolini, Marcello ; Greene, Geoffrey L

BACKGROUND:

Several mechanisms are involved in the resistance to endocrine therapy (ET) in estrogen receptor (ERα)-positive breast cancer (BC), including acquired mutations of ERα gene (ESR1). For example, the frequent mutation, Y537S, was shown to trigger a constitutively active receptor leading to reduced affinity for both agonist and antagonist ligands. The development of more comprehensive therapies remains a challenge in BC patients exhibiting activating mutations in ERα. Here, we show that Poly (ADP-ribose) polymerase-1 (PARP-1) may be considered as a novel therapeutic target in ERα-positive BC.

METHODS:

ERα wild type or Y537S mutated MCF7 and T47D BC cell lines were used as model systems. Immunoblotting, immunofluorescence, gene silencing, real-time PCR, promoter assays, chromatin immunoprecipitation sequencing (ChIP-seq) as well as cell viability, colony and cell cycle assays served to investigate the involvement of PARP-1 in BC progression. The growth of MCF7 ERα Y537S cells injected into the mammary ducts of NSG mice and treated with the ERα antagonist lasofoxifene or the PARP-1 inhibitor niraparib was monitored by luminescence imaging, weight measurement, and histological analysis. RNA sequencing studies were performed on the above-described xenograft tumors. METABRIC dataset was used to evaluate the clinical significance of PARP-1 and the biological role of the PARP-1-associated genes in ERα-positive BC patients.

RESULTS:

We first demonstrated that the up-regulation of PARP-1 expression induced by estrogens is abrogated either by inhibiting or silencing ERα in MCF7 and T47D BC cells expressing ERα wild type or Y537S mutation. We then showed that PARP-1 is involved in the binding of ERα and its co-activator FoxA1 to the promoters of several target genes, as determined by ChIP-sequencing studies. Of note, the inhibition of PARP-1 prevented the proliferative effects mediated by ERα in BC cells expressing either wild type or Y537S ERα. In accordance with these findings, the growth of xenograft tumors derived from MCF7 ERα Y537S BC cells was significantly reduced using niraparib and lasofoxifene. Finally, RNA-sequencing analyses showed that ERα signaling is downregulated by niraparib compared to vehicle-treated tumors.

CONCLUSIONS:

Overall, our results suggest that PARP-1 should be explored as a potential target in comprehensive therapeutic approaches in ET-resistant BC.

2025-05-03·Future Oncology

ELAINE 3: phase 3 study of lasofoxifene plus abemaciclib to treat ER+/HER2-, ESR1 -mutated, metastatic breast cancer

Article

作者: Boruta, Gina ; Gal-Yam, Einav Nili ; de Nonneville, Alexandre ; Wander, Seth A. ; Twelves, Chris ; Goetz, Matthew P. ; Shen, Sherry ; Damodaran, Senthil ; Bachelot, Thomas ; Portman, David J. ; Sammons, Sarah L.

Endocrine therapy (ET) is recommended for patients with estrogen receptor-positive (ER+) metastatic breast cancer (mBC), but most patients will develop treatment resistance, often due to mutations in the ER-α-coding gene, ESR1. Therapeutic options are limited for endocrine-resistant mBC, particularly following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). Lasofoxifene had anti-tumor activity in two separate phase 2, open-label studies (ELAINE 1 and 2) when given as monotherapy or combined with abemaciclib. The phase 3, randomized ELAINE 3 trial will evaluate the efficacy and safety of lasofoxifene/abemaciclib versus fulvestrant/abemaciclib for locally advanced or metastatic, ER+/HER2- breast cancer with an ESR1 mutation that progressed after ET-CDK4/6i treatment. Enrollment is planned for up to 500 patients to evaluate progression-free survival as the primary endpoint.Clinical trial registration: www.clinicaltrials.gov identifier is NCT05696626.

2025-04-01·Clinical Breast Cancer

Effects of Lasofoxifene Versus Fulvestrant on Vaginal and Vulvar Symptoms in Patients With ESR1-Mutated, ER+/HER2-, Metastatic Breast Cancer From the ELAINE 1 Study

Article

作者: Goldfarb, Shari B ; Meisel, Jane L ; Portman, David J ; Carroll, Dominic ; Jenkins, Simon N ; Pluard, Timothy J ; Komm, Barry S ; Sammons, Sarah L

BACKGROUND:

Lasofoxifene, a novel endocrine therapy (ET), showed antitumor activity versus fulvestrant in women with ESR1-mutated, metastatic breast cancer (mBC) that progressed on prior ET (phase 2, ELAINE 1 study). We investigated changes in genitourinary syndrome of menopause (GSM) vulvar-vaginal symptoms with lasofoxifene and how patient/disease characteristics affect baseline vulvar-vaginal symptoms in ELAINE 1.

METHODS:

Women were randomized to oral lasofoxifene 5 mg/day or IM fulvestrant 500 mg (days 1, 15, and 29, then every 28 days) until disease progression/severe toxicity. Changes in mean vaginal (VAS) and vulvar (VuAS) assessment scales, and their composite (average of all symptom scores/patient), from baseline to week 16, and mean baseline VAS/VuAS scores by patient/disease characteristics, were descriptively summarized.

RESULTS:

Of 103 enrolled patients, 72 (70%) completed the VAS/VuAS (mean age 61.5 years). Vaginal (40%)/vulvar (25%) dryness and vaginal pain (22%) were the most frequently reported symptoms; 26% reported ≥1 moderate/severe symptom. Lasofoxifene decreased the mean composite VAS/VuAS, VAS, and VuAS from baseline to week 16 by 74%, 74%, and 79%, respectively; fulvestrant increased them by 36%, 15%, and 63%, respectively. Baseline vaginal/vulvar symptoms were more severe if patients were under age 40, had no visceral disease, used adjuvant tamoxifen previously, or had longer AI duration in the adjuvant/metastatic settings.

CONCLUSIONS:

Oral lasofoxifene (5 mg/day), but not fulvestrant, appears to improve GSM vaginal symptoms in women with mBC. These preliminary findings suggest further study is needed; such will be explored in the phase 3, registrational, ELAINE 3 trial in patients with ESR1-mutated, ER+/HER2- mBC.

项与 Lasofoxifene Tartrate 相关的新闻（医药）

2025-07-25

·复宏汉霖

从中国首个到行业标杆 | 汉曲优®获批上市5周年，惠及全球26万患者

2025年7月，复宏汉霖乳腺癌治疗重磅产品汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）迎来了全球获批上市五周年。汉曲优®是中国、欧盟、美国获批的“中国籍”单抗生物类似药，已在全球50多个国家和地区获批上市，全球发货750多万支，对外授权覆盖超过100个国家和地区，惠及全球超过26万患者。复宏汉霖深耕乳腺癌领域五载，从首个中国曲妥珠单抗汉曲优®，到强化辅助治疗奈拉替尼领导品牌汉奈佳®，再到覆盖更广分型与治疗阶段的创新布局，致力于打造乳腺癌全程全域全球治疗生态，不让一个乳腺癌患者落下。首个中国曲妥珠单抗，惠及全球患者的行业标杆作为中国首个自主研发的曲妥珠单抗，汉曲优®以国际品质重新塑造了HER2阳性乳腺癌的治疗格局。2020年，汉曲优®分别获得欧盟和中国批准，开启了中国生物药出海先河；2024年成功登陆美国市场，成为中美欧三地获批的“中国籍”单抗生物类似药，印证了中国生物医药行业在全球市场的竞争力。这款由中国企业完全自主开发和生产的生物药，不仅填补了国产曲妥珠单抗的空白，更凭借150mg/60mg双规格设计和无防腐剂配方，推动中国乳腺癌治疗迈入精准化、安全化的曲妥珠单抗2.0时代。作为中国生物药出海典范，汉曲优®目前已在全球50多个国家和地区获批上市，覆盖欧美主流市场和众多新兴市场，对外授权超过100个国家和地区，全球累计发货量突破750万支。此外，该款药物已成功纳入中国、英国、法国、德国等多个国家的医保体系，累计惠及全球超过26万HER2阳性乳腺癌和胃癌患者。其国际化的成功离不开坚实的临床证据支持——由徐兵河院士领衔的全球多中心III期临床研究（HLX02-BC01）覆盖89个研究中心[1]，最新3年随访数据于2025年2月发表在国际权威期刊The Breast，确证了其与原研药相当的疗效和安全性。从国产首个的突破到出海全球的先驱，汉曲优®不仅展现了复宏汉霖卓越的研发实力，更见证了中国创新生物制药企业在全球医药格局中的崛起。汉曲优®的全球商业化征程，为后续中国药物的国际化发展提供了宝贵经验。如今，汉曲优®已成为中国生物药走向世界的标杆，正在持续为全球乳腺癌患者提供高质量、可负担的治疗选择。构建乳腺癌全程全域治疗生态，不让一个乳腺癌患者落下乳腺癌是全球女性发病率和死亡率最高的癌症，据GLOBOCAN数据显示，2022年全球乳腺癌新发病例达230万，死亡病例67万[2]。复宏汉霖长期深耕乳腺癌治疗领域，以“不让一个乳腺癌患者落下”为使命，通过自主研发与战略合作双轮驱动，打造覆盖乳腺癌全分型的治疗生态。在HER2阳性治疗领域，公司已形成从新辅助到强化辅助的完整治疗闭环，汉曲优®（曲妥珠单抗）作为治疗基石，与强化辅助治疗药物汉奈佳®（奈拉替尼）形成序贯治疗方案，显著降低早期患者复发风险；同时，自主研发的帕妥珠单抗生物类似药HLX11已获中美欧监管机构受理上市申请，未来拟与汉曲优®组成双靶联合方案，为患者带来更优治疗效果。针对乳腺癌其他更多亚型，复宏汉霖在研新型内分泌疗法HLX78（拉索昔芬）治疗ESR1突变的ER+/HER2-乳腺癌的国际多中心III期临床研究已于2024年12月完成中国首例患者给药。公司创新型抗HER2单抗HLX22联合德曲妥珠单抗治疗HER2低表达HR阳性乳腺癌的II期临床研究（HLX22-BC201）已于2025年4月完成中国首例患者给药，有望为HER2低表达患者带来新的治疗方案。此外，公司还依托创新技术平台推进多元药物的开发，积极布局更多难治分型的创新疗法。复宏汉霖将持续深化乳腺癌全程全域治疗布局，为全球患者带来更多更优的治疗选择。五载耕耘，全球绽放。从汉曲优®的国际化破冰到全线治疗方案的精心布局，复宏汉霖正在书写中国创新生物制药企业的全球答卷。站在新的起点，复宏汉霖将以更开放的姿态拥抱全球合作，以更创新的研发回应临床需求，以更完善的生态服务患者全程。让每一款药物的诞生都承载希望，让每一次治疗的选择都充满可能——这是复宏汉霖对"不让一个乳腺癌患者落下"承诺的最好诠释。在攻克乳腺癌的征途上，复宏汉霖将继续与全球合作伙伴携手，用中国智慧为世界健康贡献更多方案，让高质量治疗触达每一个需要的角落。参考文献[1] Xu B, Zhang Q, Sun T, et a;. Efficacy, Safety, and Immunogenicity of HLX02 Compared with Reference Trastuzumab in Patients with Recurrent or Metastatic HER2-Positive Breast Cancer: A Randomized Phase III Equivalence Trial. BioDrugs. 2021 May;35(3):337-350.[2] International Agency for Research on Cancer. Global Cancer Observatory: Cancer Today [DB/OL]. http://gco.iarc.who.int/today [2024-02-01]关于复宏汉霖复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已有6款产品在中国获批上市，4款产品在国际获批上市，5个上市申请分别获中国药监局、美国FDA和欧盟EMA受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，公司商业化生产基地已相继获得中国、欧盟和美国GMP认证。复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖约50个分子，并全面推进基于自有抗PD-1单抗H药汉斯状®的肿瘤免疫联合疗法。截至目前，公司已获批上市产品包括国内首个生物类似药汉利康®（利妥昔单抗）、自主研发的中美欧三地获批单抗生物类似药汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）、汉达远®（阿达木单抗）、汉贝泰®（贝伐珠单抗）、全球首个获批一线治疗小细胞肺癌的抗PD-1单抗汉斯状®（斯鲁利单抗，欧洲商品名：Hetronifly®）以及汉奈佳®（奈拉替尼）。公司亦同步就19个产品在全球范围内开展30多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。From China’s First to Industry Benchmark | Five Years Since HANQUYOU's Global Approval, Benefiting over 260,000 Patients WorldwideIn July 2025, Henlius celebrates the fifth anniversary of the global approval of its blockbuster breast cancer therapy, HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe). As the first "China-developed" monoclonal antibody (mAb) biosimilar approved in China, the EU, and the U.S., HANQUYOU has been launched in over 50 countries and regions worldwide, with more than 7.5 million units shipped globally. Its out-licensing covers over 100 countries and regions, benefiting more than 260,000 patients worldwide. Over the past five years, Henlius has been deeply engaged in the breast cancer field—starting with HANQUYOU, the first Chinese trastuzumab biosimilar; then with HANNAIJIA(neratinib), the leader in extended adjuvant therapy; and now with an innovative pipeline covering more subtypes and treatment stages—committed to building a full-course, all-domain, global breast cancer treatment ecosystem, with the mission of "leaving no breast cancer patient behind". China’s First Trastuzumab Biosimilar: A Benchmark Benefiting Patients Worldwide As China’s first independently developed trastuzumab, HANQUYOU has reshaped the treatment landscape for HER2-positive breast cancer with international quality. In 2020, HANQUYOU received approvals from both the European Union and China, pioneering the internationalization of China’s biosimilars. In 2024, it successfully entered the U.S. market, becoming the first "China-developed" mAb biosimilar approved in China, the U.S., and Europe—demonstrating the global competitiveness of China’s biopharmaceutical industry. Entirely developed and manufactured by a Chinese company, this biologic not only filled the domestic gap for trastuzumab but also ushered in the era of "Trastuzumab 2.0" in China with dual dosage strengths (150mg/60mg) and preservative-free formulation for more precise and safer treatment. HANQUYOU’s international journey has become a model for Chinese biosimilars going global. It is now approved in over 50 countries and regions, covering major markets in Europe and the U.S. as well as many emerging markets, with out-licensing agreements in over 100 countries and regions and total shipments exceeding 7.5 million units. Furthermore, HANQUYOU has been included in the national medical insurance catalogues of countries such as China, the UK, France , and Germany, ultimately benefiting over 260,000 patients with HER2-positive breast and gastric cancer worldwide. This global success is underpinned by robust clinical evidence—led by Academician Binghe Xu, the global multicenter Phase III trial HLX02-BC01 covered 89 research centers [1]. Its latest three-year follow-up data, published in the prestigious journal The Breast in February 2025, confirmed comparable efficacy and safety to the originator trastuzumab. From a domestic breakthrough to a pioneer in global markets, HANQUYOU showcases Henlius' strong R&D capabilities and testifies to the rise of China's innovative biopharma industry in the global landscape. Its global commercialization journey has provided valuable experience for the internationalization of other Chinese medicines. Today, HANQUYOU stands as a benchmark for Chinese biologics going global, continually offering high-quality, affordable treatment options for breast cancer patients worldwide. Building a Full-Course, All-Domain Breast Cancer Treatment Ecosystem: Leaving No Patient Behind The breast cancer is the cancer with highest incidence and mortality rates among women globally. According to the data from GLOBOCAN, there were 2.3 million new cases of breast cancer worldwide and 670,000 deaths in 2022[2]. With the mission of "leaving no breast cancer patient behind", Henlius is creating a comprehensive treatment ecosystem covering all breast cancer subtypes through independent R&D and strategic collaborations. In the HER2-positive breast cancer segment, Henlius has established a complete treatment loop from neoadjuvant to extended adjuvant therapy: HANQUYOU(trastuzumab) as the treatment cornerstone, sequentially combined with HANNAIJIA(neratinib) for extended adjuvant therapy, significantly reducing recurrence risk in early-stage patients. Meanwhile, Henlius’ pertuzumab biosimilar HLX11 has filed marketing applications with regulators in China, the U.S., and Europe and will be potentially combined with HANQUYOU for dual-target therapy to bring better outcomes for patients. For the treatment of other subtypes, Henlius' HLX78 (lasofoxifene), an investigational novel endocrine therapy for breast cancer, completed first patient dose in China for phase 3 MRCT on ER+/HER2- breast cancer in December 2024. Notably, the company’s novel anti-HER2 antibody HLX22, in combination with trastuzumab deruxtecan(T-DXd), has entered a phase 2 clinical trial (HLX22-BC201) in HER2-low, HR-positive breast cancer, with the first patient dosed in China in April 2025—potentially addressing unmet needs in this field. Moreover, leveraging its innovative technology platforms, Henlius is actively developing more therapies for hard-to-treat subtypes, continuously enriching its treatment ecosystem to offer better options for patients globally. In the past five years, from HANQUYOU's breakthrough in international markets to a carefully built full treatment portfolio, Henlius is writing the global story of Chinese innovative biopharma. Standing at a new starting point, Henlius embraces global collaboration with openness, responds to clinical needs with innovation, and serves patients comprehensively through an integrated ecosystem. Making every drug a beacon of hope and every treatment choice full of possibilities—this is Henlius’ best interpretation of its promise to "leave no breast cancer patient behind." On the journey to defeat breast cancer, Henlius will continue to partner with global collaborators, contributing Chinese innovation to global health and delivering high-quality treatment to every corner of the world.About HenliusHenlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases and ophthalmic diseases. Up to date, 6 products have been launched in China, 4 have been approved for marketing in overseas markets, and 5 marketing applications have been accepted for review in China, the U.S. and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP.Henlius has pro-actively built a diversified and high-quality product pipeline covering about 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. To date, the company's launched products include HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab), HANBEITAI (bevacizumab), HANSIZHUANG (serplulimab, trade name: Hetronifly® in Europe), the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, and HANNAIJIA (neratinib). What’s more, Henlius has conducted over 30 clinical studies for 19 products, expanding its presence in major markets as well as emerging markets.联系方式媒体：PR@Henlius.com投资者：IR@Henlius.com喜欢本文内容点击下方按钮·分享 ·收藏 ·点赞 ·在看

上市批准临床3期生物类似药

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

2025-04-11

·sermonixpharma.com

Sermonix Pharmaceuticals’ Lasofoxifene Is Well Tolerated, Demonstrates Promising Ki67 Suppression in Phase 2 I-SPY 2 Arm Evaluating Therapy in Neoadjuvant Breast Cancer Setting

COLUMBUS, Ohio, and SAN FRANCISCO, Nov. 02, 2024 (GLOBE NEWSWIRE) — Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers (mBC), and Quantum Leap Healthcare Collaborative™ today broadly announced that in the Phase 2 clinical trial evaluating lasofoxifene as a neoadjuvant endocrine therapy in molecularly selected HR+/HER2-, locally advanced breast cancer, the investigational drug was well tolerated and demonstrated promising early activity in suppressing the Ki67 protein in both premenopausal and postmenopausal patients. Results from the study, an arm of the Endocrine Optimization Pilot Protocol (EOP), a sub-study of Quantum Leap’s ongoing I-SPY 2 TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis 2), were initially shared yesterday in a poster presentation at RISE UP for Breast Cancer. Twenty patients (10 pre- and nine postmenopausal women, and one male) were enrolled in the lasofoxifene arm of the study, during which early Ki67 suppression in premenopausal patients was seen in the absence of ovarian function suppression (OFS). Ki67 is a marker that measures how fast cancer cells are dividing. “Lasofoxifene continued to demonstrate a strong tolerability profile while showing promising Ki67 suppression in this Phase 2 study, supporting our plans to further explore its potential in the neoadjuvant setting,” said Dr. David Portman, Sermonix founder and chief executive officer. “We are currently studying lasofoxifene in the ELAINE-3 Phase 3 combination study with abemaciclib in the ESR1-mutated metastatic breast cancer setting. We are excited to see it continue to demonstrate broad potential while offering unique quality of life benefits for people confronted with breast cancer.” Patients were enrolled in the I-SPY 2 arm from March 2023 to May 2024. Median total days of treatment was 154 days. At the time of data analysis, three patients were still on treatment and two discontinued treatment due to physician or patient preference. Median Ki67 expression went from 10% at baseline (range 1.0-40%) to 4% (1.0-18.0%) at Week 3. At three weeks, Ki67 expression was suppressed to <10% in 14 out of 16 (88%) patients, and to <2.7% in 6 out of 16 (38%) patients. Adverse events (AEs) were all grade 1-2. Most common AEs include hot flushes (65%), constipation (40%), fatigue (40%) and nausea (25%). “The I-SPY 2 EOP provides a biomarker-rich platform to test novel endocrine agents in the neoadjuvant setting in a molecularly selected group of patients with tumors that are predicted to have little to no benefit from chemotherapy,” said Dr. Jo Chien, principal investigator of the sub-study. “Lasofoxifene has demonstrated significant activity based on early Ki67 suppression, not only in postmenopausal women, but also in 10 premenopausal women without concomitant ovarian function suppression, with baseline Ki67 of 12.5% (1.0-40.0%) going to 3.0% (1.0-15%) at Week 3. It is exciting to see that lasofoxifene is well-tolerated even in our youngest patients who are often most impacted by the debilitating side effects of current standard endocrine therapy options.” Quantum Leap partners with a consortium that includes the U.S. Food and Drug Administration (FDA), industry, patient advocates, philanthropic sponsors and clinicians from 41 major U.S. cancer research centers. About LasofoxifeneLasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc., has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy, could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer. About SermonixSermonix Pharmaceuticals Inc. is a privately held biopharmaceutical company focused on the development of female-specific oncology products and is currently undertaking a Phase 3 clinical study of lasofoxifene, its lead investigational drug. The Sermonix management team, led by founder Dr. David Portman, has significant experience in all stages of the drug development, regulatory and commercialization processes. Paul Plourde, M.D., vice president of oncology clinical development, has many decades of experience at AstraZeneca in the breast cancer drug development arena. Barry Komm, Ph.D., chief scientific officer, is recognized for his expertise in nuclear receptor biology. Miriam Portman, M.D., is co-founder and chief operating officer, with expertise in clinical trial conduct and patient recruitment. Elizabeth Attias, M.M.Sc., Sc.D., chief strategy and development officer, has extensive experience in pharmaceutical drug commercialization. Simon Jenkins, Ph.D., vice president of operations, has over 30 years of experience in global drug development leadership. Sermonix non-executive chairman of the board is Anthony Wild, Ph.D., former president of both Parke-Davis Pharmaceuticals and Warner-Lambert’s Pharmaceutical Division. Learn more at SermonixPharma.com. To learn more about the ELAINE studies, visit DiscoverElaine.com. About Quantum Leap Healthcare CollaborativeQuantum Leap Healthcare Collaborative (QLHC) is a 501c(3) nonprofit pioneer that designs, implements, and succeeds at building and iterating creative and nimble solutions that drive meaningful results for patients. Our mission is to better serve patients by accelerating and innovating health care through approaches that challenge the status quo of science and care. All our efforts focus on achieving our long-term vision to improve human health for all through personalized medicine by bridging the gap between research and care. QLHC provides operational, financial, and regulatory oversight to I-SPY. For more information, visit https://www.quantumleaphealth.org/. About the I-SPY TRIALsThe I-SPY TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis 2) (I-SPY 2 TRIAL) was designed to rapidly screen promising experimental treatments and identify those most effective in specific patient subgroups based on molecular characteristics (biomarker signatures). The trial is a unique collaborative effort by a consortium that includes the Food and Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from 30 major U.S. cancer research centers. Under the terms of the collaboration agreement, Quantum Leap Healthcare Collaborative is the trial sponsor and manages all study operations. For more information, visit www.ispytrials.org. Quantum Leap Healthcare Collaborative Media Contact:Jacqueline MurrayDirector, Marketing and Communications(415) 839-8082j.murray@quantumleaphealth.org

临床2期临床3期临床结果

100 项与 Lasofoxifene Tartrate 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Lasofoxifene Tartrate	G03	DB06202

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
绝经期后骨质疏松	欧盟	Dr. Friedrich Eberth Arzneimittel GmbH	2009-02-24
绝经期后骨质疏松	冰岛	Dr. Friedrich Eberth Arzneimittel GmbH	2009-02-24
绝经期后骨质疏松	列支敦士登	Dr. Friedrich Eberth Arzneimittel GmbH	2009-02-24
绝经期后骨质疏松	挪威	Dr. Friedrich Eberth Arzneimittel GmbH	2009-02-24

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
萎缩性阴道炎	申请上市	美国	Sermonix Pharmaceuticals LLC	-
ER阳性/HER2阴性/ESR1突变乳腺癌	临床3期	美国	上海复宏汉霖生物技术股份有限公司	2023-11-14
ER阳性/HER2阴性/ESR1突变乳腺癌	临床3期	澳大利亚	上海复宏汉霖生物技术股份有限公司	2023-11-14
ER阳性/HER2阴性/ESR1突变乳腺癌	临床3期	加拿大	上海复宏汉霖生物技术股份有限公司	2023-11-14
ER阳性/HER2阴性/ESR1突变乳腺癌	临床3期	法国	上海复宏汉霖生物技术股份有限公司	2023-11-14
ER阳性/HER2阴性/ESR1突变乳腺癌	临床3期	以色列	上海复宏汉霖生物技术股份有限公司	2023-11-14
ER阳性/HER2阴性/ESR1突变乳腺癌	临床3期	新加坡	上海复宏汉霖生物技术股份有限公司	2023-11-14
ER阳性/HER2阴性乳腺癌	临床3期	美国	Sermonix Pharmaceuticals LLC	2023-10-31
ER阳性/HER2阴性乳腺癌	临床3期	中国	Sermonix Pharmaceuticals LLC	2023-10-31
ER阳性/HER2阴性乳腺癌	临床3期	澳大利亚	Sermonix Pharmaceuticals LLC	2023-10-31

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临床结果

适应症

分期

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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


NCT01042379 (I-SPY2 endocrine optimization pilot (EOP), ASCO2025)	临床2期	HR阳性/HER2阴性乳腺癌新辅助 MammaPrint (MP) low risk \| Ki-67 \| ctDNA+	20	Lasofoxifene 5 mg	製糧構構鏇窪衊夢鑰窪(壓網齋範繭顧網繭觸願) = 50% 醖憲遞壓獵網艱壓繭齋 (願築築淵憲獵膚窪窪鬱 ) 更多	积极	2025-05-30
				Placebo
NCT01042379 (I-SPY 2, Company_Website) 人工标引	临床2期	HR阳性/HER2阴性乳腺癌新辅助 Hormone Receptor Positive \| HER2 Negative	20	Lasofoxifene	選積齋襯鏇衊艱築簾鹽(遞願繭餘襯糧膚衊製觸) = Adverse events (AEs) were all grade 1-2. Most common AEs include hot flushes (65%), constipation (40%), fatigue (40%) and nausea (25%). 願構膚窪獵鏇憲網選夢 (糧膚淵糧築選醖鬱願艱 )	积极	2025-04-11
NCT04432454 (ELAINE 2, Pubmed \| Ann Oncol)	临床2期	ER阳性/HER2阴性/ESR1突变乳腺癌 ESR1 mutation	-	Lasofoxifene 5 mg/day + Abemaciclib 150 mg b.i.d	齋廠顧憲鹽齋築選選遞(齋艱鏇顧積廠憲選蓋蓋) = 範齋製鬱糧襯壓餘壓積齋窪築鹽窪衊願膚範淵 (鹽糧鑰廠鬱鏇廠窪衊網, 47.3% ~ 80.1%) 更多	积极	2023-12-01
NCT03781063 (ELAINE 1, Pubmed \| Ann Oncol)	临床2期	ER阳性/HER2阴性/ESR1突变乳腺癌 ESR1 mutation	103	Lasofoxifene 5 mg	糧觸繭顧鹽築選鑰鹽夢(觸廠網餘顧衊淵範鏇鏇) = 齋鹹鹹憲襯壓衊顧觸夢艱壓夢窪糧廠製願窪蓋 (醖蓋繭膚繭網窪衊製蓋 ) 更多	积极	2023-12-01
				Fulvestrant 500 mg	糧觸繭顧鹽築選鑰鹽夢(觸廠網餘顧衊淵範鏇鏇) = 蓋鹽夢遞觸壓範獵網鏇艱壓夢窪糧廠製願窪蓋 (醖蓋繭膚繭網窪衊製蓋 ) 更多
NCT04432454 (ELAINE 2, ASCO2023) 人工标引	临床2期	ER阳性/HER2阴性/ESR1突变乳腺癌 ESR1 \| ER Positive \| HER2 Negative	29	Lasofoxifene 5 mg/day + Abemaciclib 150 mg	窪糧淵艱膚壓築廠廠淵(艱襯遞鹽蓋繭網觸鏇膚) = LAS/Abema was well tolerated with primarily grade 1/2 treatment-emergent adverse events (most commonly diarrhea, nausea, fatigue, and vomiting) 遞觸積繭壓憲餘淵鏇艱 (顧膚襯獵夢製製繭簾鬱 )	积极	2023-05-31
NCT03781063 (ELAINE 1, SABCS2023)	临床2期	ER阳性/HER2阴性乳腺癌 mutESR1	103	Lasofoxifene 5 mg daily	襯壓廠簾夢襯餘壓鹹網(繭襯網襯鹽築窪簾積艱) = 廠襯夢觸膚鹹壓顧鏇壓鏇網鹹選廠膚餘築製範 (鑰壓觸鹽餘襯壓範餘蓋 ) 更多	积极	2023-03-01
				Fulvestrant 500 mg on days 1, 15, and 29, then every 4 wks	襯壓廠簾夢襯餘壓鹹網(繭襯網襯鹽築窪簾積艱) = 蓋構築衊築願醖鬱積築鏇網鹹選廠膚餘築製範 (鑰壓觸鹽餘襯壓範餘蓋 ) 更多
NCT03781063 (ELAINE 1, ESMO2022) 人工标引	临床2期	ER阳性/HER2阴性乳腺癌二线 ER+/HER2-/ESR1-mutated	103	lasofoxifene	網艱齋壓壓餘製獵願膚(廠蓋醖鏇構觸鏇繭襯鬱) = 願窪積膚醖窪鹹簾選顧繭範繭鏇簾襯襯鏇齋鹽 (繭繭遞觸選顧網餘築顧, 2.82 ~ 8.04) 更多	优效	2022-09-10
				fulvestrant	網艱齋壓壓餘製獵願膚(廠蓋醖鏇構觸鏇繭襯鬱) = 願構鹹夢獵鑰繭繭網醖繭範繭鏇簾襯襯鏇齋鹽 (繭繭遞觸選顧網餘築顧, 2.93 ~ 6.04) 更多
NCT04432454 (ELAINE 2, ASCO2022)	临床2期	ER阳性/HER2阴性乳腺癌 \| 转移性乳腺癌	29	Lasofoxifene 5 mg/day + Abemaciclib 150 mg BID	餘鹽鹽糧網餘願衊鏇顧(選構膚製壓鹽鏇積範艱) = 獵網築鬱蓋艱憲構餘範網獵構繭遞選鏇遞選廠 (觸糧範襯膚窪齋繭憲艱, 44.0–77.3) 更多	-	2022-06-02
NCT00141323 (PEARL, Pubmed \| Circulation)	临床3期	绝经期后骨质疏松	8,556	Lasofoxifene 0.5 mg/d	襯餘齋糧觸願衊齋齋網(廠膚壓憲鏇獵觸獵築壓): hazard ratio = 0.56 (95% CI, 0.32 ~ 0.98) 更多	-	2010-10-26
				Placebo
NCT00141323 (Pubmed \| N Engl J Med)	临床3期	绝经期后骨质疏松	8,556	Lasofoxifene 0.25 mg	膚遞膚築廠夢鬱廠遞糧(遞憲顧範憲餘願獵選積) = 製製製簾顧選鬱製繭廠繭膚遞觸襯構觸膚範衊 (簾獵鑰壓顧範襯願衊顧 ) 更多	-	2010-02-25
				Lasofoxifene 0.5 mg	膚遞膚築廠夢鬱廠遞糧(遞憲顧範憲餘願獵選積) = 顧壓築衊網鹽壓鏇鏇衊繭膚遞觸襯構觸膚範衊 (簾獵鑰壓顧範襯願衊顧 ) 更多