Randomised Phase II open-label window of opportunity trial AKTivate - Identifying target engagement and biomarkers of response, including an imaging biomarker, in participants receiving Capivasertib plus Exemestane and Capivasertib alone in post-menopausal participants with oestrogen receptor positive (ER+) early-stage breast cancer

开始日期2025-10-01

申办/合作机构

Cambridge University Hospitals NHS Foundation Trust

NCT06613516

/ Not yet recruiting临床2期IIT

CaptAin - Effect of Capivasertib on ctDNA in ER Positive Breast Cancer

There is growing evidence that cancer DNA (called circulating tumour DNA - ctDNA) in the blood is often an early sign that the cancer is likely to return. The aim of this study is to investigate whether treating women who have detectable ctDNA in their blood with a drug called Capivasertib can help control ctDNA levels and prevent developing metastatic or secondary breast cancer.
A recruitment of 20 women with oestrogen receptor (ER) positive breast cancer (who are already on standard of care hormone therapy who are being treated with curative intent) is aimed for; which means that the disease has not yet spread to distant parts of the body. Each subject will be dosed with 400mg of Capivasertib twice a day for a maximum period of two years.

开始日期2025-02-01

申办/合作机构

Imperial College London

[+3]

NCT06764186

/ Recruiting临床3期

A Phase IIIB Study to Evaluate the Use of Capivasertib in Combination With Fulvestrant in Patients With HR+ / HER2- Advanced Breast Cancer Who Have Relapsed/Progressed on ET and CDK4/6 Inhibitor Reflecting Real World Clinical Practice in Spain

The purpose of this study is to evaluate the effectiveness and safety of capivasertib + fulvestrant treatment administration in patients with locally advanced (inoperable) or metastatic HR+ / HER2- breast cancer with PIK3CA/AKT1/PTEN-altered following recurrence or progression on or after endocrine therapy and CDK4/6 inhibitor.

开始日期2025-01-07

申办/合作机构

AstraZeneca PLC

[+2]

100 项与卡帕塞替尼相关的临床结果

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100 项与卡帕塞替尼相关的转化医学

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100 项与卡帕塞替尼相关的专利（医药）

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411

项与卡帕塞替尼相关的文献（医药）

2025-12-01·CANCER CHEMOTHERAPY AND PHARMACOLOGY

An exposure–safety analysis to support the dosage of the novel AKT inhibitor capivasertib

Article

作者: González-García, Ignacio ; Cullberg, Marie ; Schiavon, Gaia ; Teruel, Carlos Fernandez ; Zhou, Diansong

Abstract:

Purpose:

This study aimed to evaluate capivasertib exposure–response relationships for clinical safety events to support dosage selection.

Methods:

Data from 277 patients with solid tumors participating in three phase 1 studies were analyzed. Capivasertib 80–800 mg was administered as monotherapy orally twice daily (BID) on continuous or intermittent (4 days on, 3 days off [4/3] or 2 days on, 5 days off [2/5]) schedules. Relationships between exposure related metrics (dose, weekly dose, AUC, AUCPWD, Cmax, and Cmin) and probability of safety endpoints (adverse event [AE] leading to dose discontinuation, AE leading to dose modification, serious AE [SAE], AE grade ≥ 3, AE grade ≥ 1, diarrhea AE grade ≥ 2, rash AE grade ≥ 2, hyperglycemia AE grade ≥ 3 and increased blood glucose > 13.9 mmol/L) were evaluated by logistic regression.

Results:

Significant exposure–response relationships were identified for all safety endpoints evaluated, except for AE grade ≥ 1. The analysis suggested that most of the safety endpoints are driven by the total weekly exposure, whereas glucose elevations are driven by the exposure achieved within a dosing interval. The probability of experiencing an AE leading to dose discontinuation, AE leading to dose modification, SAE, AE grade ≥ 3, diarrhea or rash were lower with the 480 mg BID [4/3] schedule than with the 320 mg BID continuous schedule.

Conclusion:

Significant exposure–response relationships were identified for safety endpoints when capivasertib was administered to patients with solid tumors suggesting that the intermittent [4/3] schedule is better tolerated than the continuous schedule due to lower total weekly exposure.

2025-04-01·CANCER TREATMENT REVIEWS

Post-progression treatment options after CDK4/6 inhibitors in hormone receptor-positive, HER2-negative metastatic breast cancer

Review

作者: Sahin, Taha Koray ; Aksoy, Sercan ; Guven, Deniz Can ; Rizzo, Alessandro

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) is the standard first-line treatment for hormone receptor-positive (HR + ) and HER2-negative metastatic breast cancer (mBC). Despite their efficacy, resistance inevitably develops, necessitating alternative therapeutic strategies post-progression. This review explores current and emerging treatment options following progression on CDK4/6i, focusing on endocrine therapies, targeted therapies, combination approaches, and the continued use of CDK4/6i. Endocrine therapies, including fulvestrant and novel oral selective estrogen receptor degraders (SERDs) like elacestrant, show promise, especially in patients with ESR1 mutations. Targeted therapies such as PI3K/AKT/mTOR inhibitors, exemplified by alpelisib and capivasertib, offer potential by addressing downstream signaling pathways involved in resistance. Additionally, FGFR inhibitors like erdafitinib are under investigation for their role in overcoming specific resistance mechanisms. Combination strategies involving CDK4/6 inhibitors with immune checkpoint inhibitors or other targeted agents are also being explored, with early trials suggesting possible synergistic effects, although further validation is required. Continuation of CDK4/6 inhibitors beyond progression has shown potential benefits in selected patients, but the data are heterogeneous, and further studies are needed to clarify their role. While chemotherapy remains a standard option for patients who progress on these treatments, the goal is to delay its use through the effective utilization of endocrine and targeted therapies. Understanding resistance mechanisms and tailoring treatment to individual patient profiles is crucial for optimizing outcomes. Ongoing clinical trials are expected to provide deeper insights, guiding the development of more effective post-progression therapeutic strategies. This evolving landscape highlights the need for continuous research and individualized patient care to improve survival and quality of life in HR + mBC patients.

2025-04-01·MOLECULAR DIVERSITY

An in silico approach to identify novel and potential Akt1 (protein kinase B-alpha) inhibitors as anticancer drugs

Article

作者: Etikyala, Umadevi ; Manga, Vijjulatha ; Dalimba, Udayakumar ; Reddyrajula, Rajkumar ; Kuchana, Vinutha ; Vani, T

Akt1 (protein kinase B) has become a major focus of attention due to its significant functionality in a variety of cellular processes and the inhibition of Akt1 could lead to a decrease in tumour growth effectively in cancer cells. In the present work, we discovered a set of novel Akt1 inhibitors by using multiple computational techniques, i.e. pharmacophore-based virtual screening, molecular docking, binding free energy calculations, and ADME properties. A five-point pharmacophore hypothesis was implemented and validated with AADRR38. The obtained R² and Q² values are in the acceptable region with the values of 0.90 and 0.64, respectively. The generated pharmacophore model was employed for virtual screening to find out the potential Akt1 inhibitors. Further, the selected hits were subjected to molecular docking, binding free energy analysis, and refined using ADME properties. Also, we designed a series of 6-methoxybenzo[b]oxazole analogues by comprising the structural characteristics of the hits acquired from the database. Molecules D1-D10 were found to have strong binding interactions and higher binding free energy values. In addition, Molecular dynamic simulation was performed to understand the conformational changes of protein-ligand complex.

256

项与卡帕塞替尼相关的新闻（医药）

2025-03-31

·同写意

第一三共 vs 阿斯利康，乳腺癌治疗，殊途同归

100+创始人齐聚海南，对话“先行先试”政策机会，共探 CGT全产业发展之路，欢迎报名！从2020年开始，乳腺癌发病率超过了肺癌发病率，成为全球第一大恶性肿瘤，是药企必争之地。罗氏曾凭借HER2单抗——曲妥珠单抗、帕妥珠单抗、HER2 ADC药物T-DM1（恩美曲妥珠单抗）等，使乳腺癌患者的生存获益显著提高，自己也成为该领域的主导者。不过花无百日红，随着核心产品迎来专利悬崖，T-DM1被DS-8201头对头击败，罗氏在乳腺癌领域的辉煌逐渐成为过去式。在后续一众虎视眈眈的围猎者中，第一三共和阿斯利康是其中的佼佼者。1DS-8201横空出世，重塑乳腺癌治疗体系作为日本百年药企，第一三共独有的DXd ADC技术平台已成为ADC新药开发的一面旗帜。其首款重磅ADC药物Enhertu（德曲妥珠单抗，DS-8201）的横空出世，更是重新点燃了全球ADC药物的研发热情。德曲妥珠单抗是一款靶向HER2的抗体偶联药物（ADC），由第一三共研发，并由第一三共和阿斯利康共同开发和商业化。HER2是一种酪氨酸激酶受体促生长蛋白，在多种肿瘤细胞表面均有表达。作为一款HER2靶向ADC，德曲妥珠单抗采用第一三共独有的DXd ADC技术设计，由靶向HER2的人源化单克隆抗体通过四肽可裂解连接子与拓扑异构酶1抑制剂（喜树碱类衍生物，DXd）有效载荷连接组成。自2019年获FDA批准上市以来（用于治疗接受过2种或以上抗HER2疗法的治疗的无法切除或转移性HER2阳性乳腺癌患者），德曲妥珠单抗就不断书写它的传奇，并一步步重塑乳腺癌治疗格局。首次惊艳业界的是与恩美曲妥珠单抗的头对头随机对照研究。DESTINY-Breast03是首个头对头比较德曲妥珠单抗和恩美曲妥珠单抗在 HER2 阳性晚期乳腺癌二线治疗中疗效的 Ⅲ 期临床研究。在2022 年圣安东尼奥国际乳腺癌研讨会（SABCS）上公布的研究结果显示，德曲妥珠单抗组无进展生存期（PFS）获益明显（28.8 个月 vs 6.8 个月），约为恩美曲妥珠单抗组的 4 倍，并且降低患者疾病进展或死亡风险67%。2022年5月，德曲妥珠单抗扩展适应症获美FDA批准，用于治疗无法切除或转移性HER2+乳腺癌患者，这些患者曾经接受过一种抗HER2靶向疗法的治疗。德曲妥珠单抗重塑了HER2+乳腺癌的二线治疗标准。随后的DESTINY-Breast04研究则更进一步，将HER2低表达（IHC 1+或2+/ISH阴性）乳腺癌确立为新的治疗亚型，开创了HER2低表达晚期乳腺癌治疗的新时代。研究结果显示，在激素受体（HR）阳性/HER2低表达乳腺癌患者中，德曲妥珠单抗组的中位PFS绝对值较化疗组延长了近5个月（10.1个月 vs 5.4个月，HR=0.51，95%CI：0.40-0.64）；中位总生存期（OS）也显著延长（23.9个月 vs 17.5个月，HR=0.64，95%CI：0.48-0.86）；德曲妥珠单抗组客观缓解率（ORR）达52.6%，而化疗组仅为16.3%。基于DESTINY-Breast04研究的出色结果，德曲妥珠单抗获得了国内外权威指南的一致推荐。美国NCCN乳腺癌指南（2022.V4版）将“HER2低表达乳腺癌（IHC 1+或IHC 2+/ISH-）”作为一种全新的治疗分型，将德曲妥珠单抗作为伴有内脏危象/内分泌难治HER2低表达乳腺癌的二线治疗方案。随后德曲妥珠单抗获批HER2低表达转移性乳腺癌适应症，使得乳腺癌治疗从传统的非阴即阳二分法时代迈入更加精准的三分法时代（阳性/低表达/阴性），不仅将受益人群扩大至60%-70%，更是推动整个抗HER2乳腺癌治疗模式的革新。据第一三共2024财年业绩，德曲妥珠单抗在HER2阳性乳腺癌二线治疗和HER2低表达乳腺癌适应症上，都实现了两位数的增长（德曲妥珠单抗2024全球销售额约34.77亿美元）。DESTINY-Breast系列研究还在继续。今年1月27日，FDA批准德曲妥珠单抗用于治疗不可切除或转移性、激素受体（HR）阳性且HER2低表达（IHC 1+或IHC 2+/ISH-）或超低表达（IHC 0但具有膜染色）的乳腺癌患者。这一批准基于DESTINY-Breast06研究，结果显示，在总人群中，德曲妥珠单抗相比标准治疗组，将中位PFS显著延长了5.1月（13.2个月 vs 8.1个月，HR=0.63，P<0.0001）；在HER2低表达患者亚组中，德曲妥珠单抗相比标准治疗组，中位PFS显著延长（13.2个月 vs 8.1个月，HR=0.62，P<0.0001），OS达到12个月的比例更高（87.6% vs 81.7%，HR=0.83）；在HER2超低表达患者亚组中，德曲妥珠单抗展现出与HER2低表达亚组相似的获益趋势，相比标准治疗组，中位PFS显著延长（13.2个月 vs 8.3个月，HR=0.78），OS达到12个月的比例更高（84.0% vs 78.7%，HR=0.75）。至此，德曲妥珠单抗从HER2阳性到HER2低表达、超低表达，都已积累了循证医学证据，重新塑造了乳腺癌治疗格局。2阿斯利康不语，只一味卷自己在乳腺癌治疗领域，阿斯利康是不能被忽视的存在。阿斯利康瞄准HR+乳腺癌患者这一大群体，陆续推出了他莫昔芬、戈舍瑞林、阿那曲唑和氟维司群四款内分泌治疗基石药物，并不断在此基础上超越自己。以经典药物氟维司群（fulvestrant）为例，这是一款选择性雌激素受体降解剂（SERD），其通过与癌细胞表面的ER相结合，降低ER的稳定性，诱导它们被细胞正常的蛋白降解机制降解，从而降低雌激素受体水平，抑制癌细胞的生长。其优势在于能够更全面地抑制雌激素受体的功能，并且可能解决雌激素受体突变产生的耐药性。2002年4月，Faslodex（氟维司群）获FDA批准上市，用于雌激素治疗（如他莫昔芬）后疾病进展的绝经后乳腺癌患者。作为全球首款SERD药物，氟维司群可将达到总生存期5年的晚期乳腺癌患者的比例，由22.5%提升至50%。在二十年的时间中，氟维司群独占SERD市场，销售峰值达到10.28亿美元。不足的是，氟维司群只能肌肉注射给药，生物利用度低且可及性欠佳。所以业界开始追求效果更强、可及性更好、极具替代潜力的SERD口服药，不过，这一路走来并不顺利。2022年，赛诺菲的SERD口服药Amcenestrant在用于局部晚期或转移性HR+/HER2-乳腺癌患者的II期临床研究，以及联合CDK4/6抑制剂哌柏西利用于HR+/HER2-晚期乳腺癌的III期研究均失败。赛诺菲遂终止Amcenestrant项目的所有临床试验。同一年，罗氏宣布其SERD口服药Giredestrant在II期研究中未能达到PFS主要终点，OS尚不成熟。2023年，在经历14年临床开发后，美纳里尼集团旗下子公司美纳里尼集团的ORSERDU（Elacestrant，艾拉司群）获FDA批准上市，用于治疗局部晚期或转移性乳腺癌的绝经后女性或者成年男性，患者具有HR+/HER2-和ESR1突变，并且接受了至少一种内分泌治疗后病情出现进展。艾拉司群成为首个成功上市的SERD口服药物。看来，SERD口服药的研发远不如想象般容易。幸运的是，阿斯利康近日也传来好消息。2月26日，阿斯利康宣布，其SERD口服药物camizestrant在治疗HR+局部进展或转移性乳腺癌患者的III期SERENA-6临床研究中达到主要终点。即camizestrant 联合CDK4/6抑制剂在PFS的主要终点方面显示出具有统计学意义和临床意义的改善。该试验新颖之处在于，利用ctDNA监测来识别患者的内分泌耐药性早期迹象和ESR1突变的出现。ESR1基因突变是内分泌耐药的关键驱动因素，大约30%的内分泌敏感HR+疾病患者在一线治疗期间出现ESR1突变。SERENA-6研究表明，在检测到ESR1突变（尚无疾病进展）后，从芳香化酶抑制剂（阿那曲唑或来曲唑）转换为camizestrant联合CDK4/6抑制剂，可以延缓疾病进展并延长一线治疗的益处。至此，Camizestrant成为了首个证明与CDK4/6抑制剂联用时具有一线治疗获益的新一代SERD口服药物。在内分泌治疗领域，阿斯利康还率先推出了AKT抑制剂Capivasertib，该药于2023年11月，获FDA批准用于治疗HR+/HER2-局部晚期或转移性乳腺癌患者，这些患者在接受内分泌基础方案治疗过程中或之后疾病复发或进展。除在内分泌治疗不断进行自我迭代外，阿斯利康还推出了全球首款PARP抑制剂——奥拉帕利，也是首个利用DNA损伤修复通路缺陷来杀死癌细胞的靶向治疗药物。目前，在乳腺癌领域，奥拉帕利获批用于辅助治疗BRCA生殖系突变（gBRCAm）的HER2阴性高危早期乳腺癌患者，这是首款也是唯一一款获得批准治疗BRCA突变早期乳腺癌患者的疗法。在乳腺癌领域，阿斯利康产品已覆盖从早期到晚期、从绝经前到绝经后的HR+乳腺癌患者。3深耕技术平台 vs 多元合作创新，都有“美好的未来”第一三共在乳腺癌领域的异军突起，来自于对平台技术数十年磨一剑的专注。其ADC研发最早可追溯至20世纪80年代，经过40年迭代，其通过靶点选择及连接子、细胞毒药物的技术优化等，打造了独特的DXd-ADC技术平台，以实现精准靶向、高效低毒的技术优势。依托该平台，第一三共改良的DXd以10倍药物活性与极强的渗透细胞膜的能力，能够更好地发挥“旁观者效应”，这也是德曲妥珠单抗对于HER2低表达乳腺癌有优异疗效的关键因素。除德曲妥珠单抗之外，第一三共还布局了6款ADC药物，包括Dato-DXd（靶向TROP2 ADC），HER3-DXd（靶向HER3 ADC）， I-DXd（B7H3 ADC）和 R-DXd（CDH6 ADC）等。其中Dato-DXd 由第一三共研发，第一三共和阿斯利康共同开发和商业化，是一款新型TROP2 ADC，具有抗肿瘤旁观者效应，且药物安全性更高。目前Dato-DXd已被日本药品与医疗器械管理局（PMDA）、FDA批准用于治疗既往接受过化疗和内分泌治疗的不可切除或转移性HR+/HER2阴性（IHC 0、IHC 1+或IHC 2+/ISH-）乳腺癌成人患者（商品名：Datroway）。此外，Dato-DXd的研究布局还拓展至三阴性乳腺癌（TNBC）的早期和晚期治疗领域。这类乳腺癌为雌激素受体（ER）阴性、孕激素受体（PR）阴性、以及HER2阴性，由于缺乏有效治疗靶点，且预后差，素有“乳腺癌之王”之称。对于TNBC，寻找新的有效疗法刻不容缓。第一三共和阿斯利康已经启动多项III期临床研究评估Dato-DXd单药或联合疗法治疗TNBC的潜力。第一三共凭借独有的DXd-ADC技术平台，在乳腺癌治疗领域后来居上，用创新实力重新定义疾病分类，重塑了乳腺癌治疗体系。阿斯利康则通过自研和外部合作，在乳腺癌领域成功搭建出了一个有规模有层次的产品管线。从他莫昔芬到氟维司群，从奥拉帕利到Capivasertib，再从氟维司群到Camizestrant，阿斯利康的产品覆盖多个前沿靶点，同时在现有药物基础上不断改良升级，占领创新高地，实现治疗场景全覆盖。对比第一三共和阿斯利康，两家药企虽然模式不同，但都心系研发，最终印证了创新突破与商业的共振逻辑。大浪淘沙，乳腺癌药物市场虽大，最终也只能奖赏专注研发、不断自我超越的真创新药企。参考文献：1.Latest global cancer data: Cancer burden rises to 19.3 million new cases and 10.0 million cancer deaths in 2020. Retrieved Nov 16 ,2020,fromhttps://www.iarc.who.int/faq/latest-global-cancer-data-2020-qa/.2.Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. The New England Journal of Medicine. 2022; 387(1):9-20.3.Curigliano G, Hu XC, Dent R, et al. Trastuzumab deruxtecan (T-DXd) vs physicians choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06). 2024 ASCO. LBA1000.4.https://www.daiichisankyo.com/files/news/pressrelease/pdf/202412/20241227_E.pdf.

抗体药物偶联物临床3期临床结果上市批准引进/卖出

2025-03-22

·精准药物

【J. Med.Chem.】从弱到强：基于片段药物设计（FBBD）的40年突破之路

基于片段的药物设计（FBDD）已成为药物发现的重要策略，与传统高通量筛选（HTS）形成互补。历经近50年发展，推动多款药物成功上市。结构与计算工具的整合，显著提升FBDD效率，助力理性药物设计。随着药物靶点向“不可成药”领域及新治疗模式延伸，FBDD在靶向复杂生物分子中展现关键潜力。持续融合前沿计算与筛选技术（如虚拟筛选、机器学习），突破药物化学瓶颈，加速创新疗法开发。小片段撬动大突破自1981年提出以来，基于片段的药物设计（FBDD）已成为药物发现的核心策略之一。其核心逻辑是筛选低分子量化合物（约150–300 Da），这些片段虽与靶蛋白结合较弱，但通过化学修饰可优化为强效药物。1990年代，“核磁共振（SAR by NMR）”技术首次实现片段筛选，随后X射线晶体学、表面等离子体共振（SPR）等方法进一步推动技术普及，使FBDD融入主流药物研发流程。成果斐然：从“不可成药”到临床突破 FBDD已催生8款FDA批准药物及超50个临床候选化合物。首款成功案例是2011年获批的黑色素瘤药物Zelboraf，其研发仅用6年。随后，多款里程碑药物涌现： Pexidartinib（2015年）：一种CSF-1R抑制剂； Venetoclax（ABT-199，2016年）：一种Bcl-2抑制剂，能够破坏蛋白–蛋白相互作用； Erdafitinib（2019年）：一种用于治疗尿路上皮癌的FGFR抑制剂； Berotralstat（BCX7353，2020年）：一种用于治疗遗传性血管水肿的丝氨酸蛋白酶抑制剂； Sotorasib（AMG 510，2021年）：一种KRAS-G12C抑制剂，针对一个被认为难以治疗的“不可药化”蛋白； Asciminib（ABL001，2021年）：一种新型的BCR-ABL1别构抑制剂； Capivasertib（AZD5363，2023年）：一种AKT激酶抑制剂。超半数药物为激酶抑制剂，但Venetoclax和Sotorasib的成功证明FBDD在难治靶点中的潜力。此外，FBDD在苗头化合物优化、靶点可药性评估中展现高效性，甚至延伸至PROTAC等新兴疗法，成为药物创新的“多面手”。图1. 过去四十年基于片段的药物设计里程碑。3D分子结构由Schrödinger 2022.3（Maestro 13.3）中的LigPrep模块生成。图2. 从基于片段的药物设计（FBDD）衍生的FDA批准药物。展示了从FBDD衍生的FDA批准药物的化学结构。基于片段的药物设计（FBDD）：优势与挑战并存（1）优势： FBDD能筛选来自广泛化学空间的小分子片段，适用于各种靶点，包括蛋白质和RNA，具有较强的靶点适应性。片段库由低分子量化合物组成，通常遵循“三原则”，这使得它们在优化时具有更大潜力。 FBDD还可以通过敏感的筛选方法检测弱结合物，这些物质通常在高通量筛选中被忽略。片段筛选的时间较短，能够显著降低成本和时间。此外，FBDD能初步评估靶点的可药物性，帮助风险评估，无需参考化合物，易于实施。片段扩展有助于探索结构-活性关系（SAR），推动新型先导化合物开发。FBDD已应用于新型治疗模式，如PROTACs，利用片段连接原理，具有低分子量和弱结合亲和力，表明其在优化新药模式中的潜力。（2）挑战：片段库质量：需平衡多样性、合成可行性与理化性质，构建高质量库难度高；筛选灵敏度：弱结合检测依赖先进技术（如NMR、X射线），设备与经验门槛较高；苗头物选择：高命中率下需结合配体效率（LE）、结合模式分析（NMR/冷冻电镜）筛选优质片段；规模压力：百万级片段库涌现，传统实验筛选难以负荷，需虚拟筛选预筛以降低成本；人工优化局限：片段扩展依赖药物化学经验，面对海量数据与复杂相互作用，效率受限。表1. 片段筛选方法筛选方法样品要求灵敏度（亲和力）优势缺点配体观察NMR（STD-NMR, Water-LOGSY, CMPG, T1rho）低（<50 μM样品） mM–nM 不需要同位素标记。无法检测紧密结合物。对靶标大小没有限制。不适用于所有靶标。灵敏度高，能检测弱结合物。无法检测紧密结合物。可在筛选中使用片段混合物。 19F-NMR 低（<50 μM样品） mM–μM 灵敏的筛选方法。片段需要用氟标记。高通量筛选方法。只能检测弱结合物。适用于蛋白质和RNA靶标。不需要靶标标记，对靶标没有大小限制。蛋白质观察NMR（HSQC, 19F-NMR）高（>10 μM, 10–100 mg） mM–nM 可检测紧密结合物和弱结合物。需要标记蛋白质。提供结构信息。筛选时间较长。确定结合位点。 X射线晶体学高（10–50 mg） mM–nM 提供结构信息。无法检测结合亲和力和特异性。检测结合模式。需要高质量的晶体进行浸泡。表面等离子共振（SPR）低（<1 mg） μM–nM 高通量筛选方法。需要将靶标固定。提供筛选中的结合动力学数据。需要参考化合物设置实验。不适用于所有靶标。不适用于检测弱结合物。等温滴定量热法（ITC）高（>10 μM样品） μM–nM 提供结合曲线来测量结合亲和力。低通量实验。确定焓变或熵驱动的结合。需要较高浓度的样品。不适用于每个靶标。需要参考化合物设置实验。不适用于检测弱结合物。热变性实验（TSA）/差示扫描荧光法（DSF）低（∼μM–nM） μM–nM 高通量筛选实验假阳性率较高。不适用于每个靶标。需要参考化合物设置实验。本征质谱法低（nM, μg–1 mg） μM–nM 高通量筛选实验需要仔细优化实验条件。只需要微克级样品。不适用于弱结合物。微尺度热泳动法（MST）低（<μM） μM–nM 能测量结合亲和力。低通量筛选方法。不适用于弱结合物。生物层干涉法（BLI）低（∼μM） μM–nM 高通量方法不适用于弱结合物。适用于确认苗头化合物。荧光偏振法（FP）低（<μM） μM–nM 高通量筛选方法不适用于弱结合物。不适用于每个靶标。需要参考化合物设置实验。表型筛选无要求 μM–nM 筛选具有良好细胞渗透性的化合物。命中率低，需要确认靶标-苗头化合物的相互作用。适用于筛选共价片段仅适用于紧密结合物。不需要纯化靶标。需要确认靶标。生化实验低（<μM） μM–nM 高通量筛选实验靶标需要具有酶活性或已被充分表征。可以直接测量片段对靶标的影响。不适用于弱结合物，导致命中率低。筛选过程中需要较高浓度的片段。虚拟筛选无要求无要求高通量方法假阳性率高。筛选过程中不需要化合物和样品。需要通过实验筛选确认苗头化合物。适合筛选百万至十亿个化合物。能够考虑多个结合口袋。展望基于片段的药物设计（FBDD）有望成为药物发现的关键驱动力。随着分子生物学和生物信息学的进展，靶标空间已扩展到RNA及RNA结合蛋白（RBPs），为治疗提供了超越传统蛋白靶标的新机遇。例如，FDA批准的RNA剪接调节剂Risdiplam，通过调节SMN2前mRNA的剪接，成功治疗了相关疾病。然而，RNA及RBPs的极性和灵活性使得传统方法难以靶向，而FBDD凭借识别小分子和弱结合片段的优势，提供了有效的探索途径。高分辨率的冷冻电子显微镜（cryo-EM）揭示了复杂的蛋白质/RNA结构，帮助发现潜在的结合位点。同时，人工智能和分子建模技术加强了对RNA和蛋白质复合物的理解，提供了更精确的药物设计线索。多样化的片段库扩展了化学空间，结合实验和计算筛选提高了命中率和靶点识别能力。 FBDD与新兴计算技术的结合，使得药物设计更加强大和多功能。未来，FBDD有望攻克难以靶向的复杂靶标，如蛋白质-蛋白质相互作用和RNA靶点。将机器学习和人工智能整合到FBDD中，将加速药物发现过程，解决未满足的医学需求。参考文献： https://pubs-acs-org.libproxy1.nus.edu.sg/doi/10.1021/acs.jmedchem.5c00424

蛋白降解靶向嵌合体上市批准临床结果

2025-03-13

·PRNewswire

VERZENIO's Market Potential Soars as Demand for CDK4/6 Inhibitors Grows | DelveInsight

As VERZENIO gains traction in early-stage treatments and broadens its approved uses, its revenue is expected to keep growing. While the global CDK4/6 inhibitor market remains highly competitive, VERZENIO's distinct clinical advantages and ongoing studies could contribute to further market expansion. LAS VEGAS, March 13, 2025 /PRNewswire/ -- DelveInsight's " VERZENIO Market Size, Forecast, and Market Insight Report" highlights the details around VERZENIO, which is a targeted treatment known as a CDK4/6 inhibitor. The drug is a non-chemotherapy oral tablet. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of VERZENIO. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Eli Lilly and Company's VERZENIO (abemaciclib) Overview VERZENIO (abemaciclib) is a prescription medication used to treat adults with HR-positive, HER2-negative breast cancer that has metastasized (spread to other parts of the body). It is administered orally and is prescribed in combination with an aromatase inhibitor as an initial endocrine-based therapy. Additionally, the drug is being developed for the treatment of prostate cancer. VERZENIO is approved for the following indications: In combination with endocrine therapy for the adjuvant treatment of adults with HR+/HER2-, node-positive, early-stage breast cancer at high risk of recurrence. In combination with an aromatase inhibitor as the initial endocrine-based therapy for adults with HR+/HER2- advanced or metastatic breast cancer. In combination with fulvestrant for adults with HR+/HER2- advanced or metastatic breast cancer that has progressed after prior endocrine therapy. As monotherapy for adults with HR+/HER2- advanced or metastatic breast cancer that has progressed following endocrine therapy and prior chemotherapy in the metastatic setting. Learn more about VERZENIO projected market size for breast cancer @ VERZENIO Market Potential HR+/HER2- breast cancer is the most common subtype of breast cancer, defined by the presence of estrogen and progesterone hormone receptors but lacking HER2 overexpression. This form of breast cancer generally has a favorable prognosis and is primarily managed with hormone therapy to suppress hormone-driven tumor growth. According to DelveInsight's estimates, around 211,000 new cases of HR+/HER2− breast cancer were reported in the US in 2024. Over the past decade, endocrine therapy has remained the cornerstone of treatment, including for cases with visceral involvement. The current preferred approach involves combining endocrine therapy—using aromatase inhibitors or fulvestrant—with CDK4/6 inhibitors. The approval of CDK4/6 inhibitors has significantly transformed the treatment landscape for HR+/HER2− breast cancer. Currently, five selective CDK4/6 inhibitors— ENHERTU, DATROWAY, IBRANCE, KISQALI, and VERZENIO—are used in combination with endocrine therapy. In November 2023, the FDA approved TRUQAP (capivasertib) in combination with FASLODEX for patients with advanced HR+/HER2− breast cancer harboring specific biomarker alterations (PIK3CA, AKT1, or PTEN). The NCCN Guidelines have designated KISQALI as the only Category 1 Preferred CDK4/6 inhibitor for first-line treatment in combination with an aromatase inhibitor, strengthening its position in the U.S. market. This led to KISQALI recovering its lost market share, with its U.S. revenue contribution rebounding to 50%, following declines to 46% in 2020, 36% in 2021, and 38% in 2022. In January 2025, the FDA approved DATROWAY for patients with unresectable or metastatic HR+/HER2- breast cancer (IHC 0, IHC 1+, or IHC 2+/ISH-) who had previously received endocrine-based therapy and chemotherapy. Additionally, ENHERTU was approved for patients with unresectable or metastatic HR+, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer that had progressed after at least one prior endocrine therapy in the metastatic setting. Also, in January 2025, Roche reported positive topline results from its Phase III INAVO120 trial, assessing ITOVEBI in combination with IBRANCE and fulvestrant for patients with PIK3CA-mutated HR+/HER2−, endocrine-resistant, locally advanced, or metastatic breast cancer. Among the seven major markets, the US accounted for the largest market share in HR+/HER2− breast cancer, generating USD 7.5 billion in revenue in 2023. The market is expected to experience substantial growth from 2025 to 2034, driven by the introduction of novel therapeutic options. Discover more about the breast cancer market in detail @ Metastatic HR+/HER2- Breast Cancer Market Report Emerging Competitors of VERZENIO Some of the competing emerging key players in HR+/HER2- breast cancer market are, Merck (KEYTRUDA), Arvinas (ARV-471 (vepdegestrant)), Olema Pharmaceuticals (OP1250 (palazestrant)), Celcuity (Gedatolisib), Roche (Giredestrant (RG6171, GDC-9545); Inavolisib), AstraZeneca and Daiichi Sankyo (Datopotamab Deruxtecan (Dato-DXd)), AstraZeneca (Camizestrant (AZD9833); Capivasertib), Eli Lilly (LY3484356/Imlunestrant), Sermonix Pharmaceuticals (Lasofoxifene), Veru Pharma (Enobosarm), DualityBio/BioNtech (DB-1303), Evgen Pharma (SFX-01), Carrick Therapeutics (Samuraciclib (CT-7001)), EQRx/G1 Therapeutics (Lerociclib), Immutep (Eftilagimod Alpha (LAG-3lg/IMP321)), and others. To know more about the number of competing drugs in development, visit @ VERZENIO Market Positioning Compared to Other Drugs Key Milestones of VERZENIO In 2024, Phase III trials did not meet primary endpoints or were terminated for futility. Negative Phase III CYCLONE-2 results, in which VERZENIO added to abiraterone did not meet the primary endpoint of improved radiographic progression-free survival (rPFS) in men with metastatic castration-resistant prostate cancer (mCRPC). In December 2023, Eli Lilly and Company presented results from the MONARCH 3 clinical trial at the 2023 San Antonio Breast Cancer Symposium (SABCS). Results from MONARCH 3 show a numerical improvement in overall survival (OS) of 13.1 months for women with HR+, HER2- metastatic breast cancer treated with VERZENIO plus an aromatase inhibitor in the intent-to-treat population and 14.9 months for women with visceral disease. In March 2023, the US FDA approved an expanded indication for VERZENIO in combination with endocrine therapy for the adjuvant treatment of adult patients with HR+/HER2−, node-positive, early breast cancer (EBC) at a high risk of recurrence. This expanded adjuvant indication removes the Ki-67 score requirement for patient selection. In February 2022, the CHMP adopted a positive opinion recommending a change to the terms of the marketing authorization for the medicinal product VERZENIO. VERZENIO, in combination with endocrine therapy, is indicated for the adjuvant treatment of adult patients with HR+/HER2− negative, node-positive early breast cancer at high risk of recurrence. In October 2021, the US FDA approved VERZENIO, in combination with endocrine therapy (tamoxifen or an aromatase inhibitor), for the adjuvant treatment of adult patients with HR+/HER2−, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of ≥20% as determined by an FDA-approved test. Ki-67 is a marker of cellular proliferation. In September 2018, VERZENIO was approved in Europe for treating advanced HR+ breast cancer in women if the cancer has already spread to other parts of the body or is locally advanced. In September 2018, VERZENIO was approved for the treatment of patients with HR+/HER2− unresectable or recurrent breast cancer in combination with fulvestrant or an aromatase inhibitor (AI) in Japan. In February 2018, the US FDA approved VERZENIO in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy for the treatment of postmenopausal women with HR+/HER2− advanced or metastatic breast cancer In September 2017, the US FDA approved VERZENIO in combination with an endocrine therapy to treat adult patients who have HR+/HER2− advanced or metastatic breast cancer that has progressed after taking therapy that alters a patient's hormones (endocrine therapy). In October 2015, the US FDA granted Breakthrough Therapy Designation to abemaciclib for patients with refractory hormone-receptor-positive (HR+) advanced or metastatic breast cancer Discover how VERZENIO is shaping the breast cancer treatment landscape @ VERZENIO Breast Cancer VERZENIO Market Dynamics The oral administration of VERZENIO enhances patient convenience, while its expanded approval for the adjuvant treatment of adult patients with HR+/HER2- early breast cancer highlights its role as a differentiated CDK4/6 inhibitor in reducing the risk of recurrence. The rising prevalence of HR+/HER2- breast cancer is driving market demand for effective treatments like VERZENIO. Additionally, its demonstrated efficacy in combination with endocrine therapy and its ability to penetrate the central nervous system further strengthen its market position. Favorable reimbursement policies and increasing awareness among healthcare providers also contribute to its adoption. However, its adoption may be hindered by regulatory hurdles and potential side effects, including severe or life-threatening lung inflammation and serious liver problems. High treatment costs and access disparities in certain regions could also limit market penetration. Competition from other CDK4/6 inhibitors such as IBRANCE and KISQALI poses a challenge, along with concerns over long-term safety data. Additionally, the Phase III CYCLONE-2 trial failed to meet primary endpoints in mCRPC, which may impact its broader clinical prospects and investor confidence. Dive deeper to get more insight into VERZENIO's strengths & weaknesses relative to competitors @ VERZENIO Market Drug Report Table of Contents Related Reports CDK4/6 Inhibitor Market CDK4/6 Inhibitor Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key CDK4/6 inhibitor companies including Pfizer, Prelude Therapeutics, G1 Therapeutics, Pepper Bio, among others. Metastatic HR+/HER2− Breast Cancer Market Metastatic HR+/HER2− Breast Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key metastatic HR+/HER2− breast cancer companies including Pfizer, Novartis, Stemline Therapeutics, Olema Pharmaceuticals, Arvinas, Immutep, AstraZeneca, Roche, Genentech, Evexta Bio, EQRx, Sermonix Pharmaceuticals, Celcuity, Veru Pharma, Evgen Pharma, Eli Lilly, Biotheryx, among others. HR+/HER2− Breast Cancer Pipeline HR+/HER2− Breast Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key HR+/HER2− breast cancer companies, including Regor Therapeuics, Seagen Inc., CytomX Therapeutics, Taizhou EOC Pharma, Chia Tai Tianqing Pharmaceutical Group, AstraZeneca, Daiichi Sankyo, Inc., Tyme, Inc., Seagen Inc., Context Therapeutics, Eisai Inc., Shanghai Hengrui Pharmaceutical Co., Ltd., Jiangsu Simcere Pharmaceutical Co., Kind Pharmaceuticals, Merus N.V., Atossa Therapeutics, Roche, among others. Breast Cancer Market Breast Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key breast cancer companies, including Veru, Sanofi, Roche, AstraZeneca, Eli Lilly, EQRx, Gilead, Sermonix Pharmaceuticals, Evgen Pharma, Tyme, Genentech, Daiichi Sankyo, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期上市批准临床结果突破性疗法ASCO会议

100 项与卡帕塞替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11371	-	-	DB12218

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
ER阳性/HER2阴性乳腺癌	欧盟	AstraZeneca AB	2024-06-17
ER阳性/HER2阴性乳腺癌	冰岛	AstraZeneca AB	2024-06-17
ER阳性/HER2阴性乳腺癌	列支敦士登	AstraZeneca AB	2024-06-17
ER阳性/HER2阴性乳腺癌	挪威	AstraZeneca AB	2024-06-17
乳腺癌	加拿大	AstraZeneca Canada, Inc.	2024-01-26
HR阳性/HER2阴性乳腺癌	美国	AstraZeneca Pharmaceuticals LP	2023-11-16

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
局部晚期乳腺癌	临床3期	西班牙	AstraZeneca PLC	2025-01-07
晚期乳腺癌	临床3期	中国	AstraZeneca AB	2024-09-26
转移性去势抵抗性前列腺癌	临床3期	美国	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	中国	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	日本	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	澳大利亚	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	比利时	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	巴西	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	加拿大	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	智利	AstraZeneca PLC	2022-03-25

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临床结果

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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


NCT04305496 (CAPItello-291, Pubmed \| J Clin Oncol)	临床3期	PIK3CA突变/HR阳性/HER2阴性乳腺癌 PIK3CA \| AKT1 \| PTEN	708	Capivasertib 400 mg twice daily with fulvestrant	憲窪膚艱網遞製積製餘(繭夢夢選鑰餘艱簾壓壓): HR = 0.6 (95% CI, 0.51 ~ 0.71) 更多	积极	2024-12-01
				Placebo with fulvestrant
NCT04556773 (DESTINY-Breast08, SABCS2024) 人工标引	临床1期	HER2低表达乳腺癌 HER2-low	60	Trastuzumab deruxtecan (T-DXd) + Capecitabine (CAPE)	範淵餘醖遞襯齋簾餘鏇(鹽餘衊獵蓋襯憲遞網壓) = 鹹廠繭衊遞憲選鹹廠鏇淵願觸構網膚願壓糧餘 (觸獵憲觸憲壓淵膚築積 ) 更多	积极	2024-11-26
				Trastuzumab deruxtecan (T-DXd) + Capivasertib (CAPI)	範淵餘醖遞襯齋簾餘鏇(鹽餘衊獵蓋襯憲遞網壓) = 遞觸鏇壓簾蓋遞齋壓艱淵願觸構網膚願壓糧餘 (觸獵憲觸憲壓淵膚築積 ) 更多
NCT04493853 (CAPItello-281, Company_Website) 人工标引	临床3期	激素依赖性前列腺癌 PTEN Deficient Expression	-	capivasertib + abiraterone + androgen deprivation therapy	壓製築願鑰淵鬱餘網積(夢製鏇糧鹽鹽衊網廠鑰) = statistically significant and clinically meaningful improvement 網餘積窪廠餘選窪鏇構 (齋網齋蓋製艱襯鏇築齋 ) 更多	积极	2024-11-25
				placebo + abiraterone + androgen deprivation therapy
NCT04305496 (CAPItello-291, Pubmed \| Future Oncol)	临床3期	HR阳性乳腺癌 PIK3CA \| AKT1 \| PTEN	-	Capivasertib plus Fulvestrant	鏇鬱鹹衊積壓醖蓋獵築(憲製遞淵齋糧醖廠膚鹽) = The most common side effects experienced by participants included diarrhea 蓋觸糧壓簾淵獵襯簾壓 (鑰鏇糧積襯範網構網遞 ) 更多	积极	2024-11-25
				Placebo plus Fulvestrant
NCT04305496 (CAPItello-291, Pubmed) 人工标引	临床3期	HR阳性/HER2阴性乳腺癌 HER2 Negative \| Hormone Receptor Positive	901	capivasertib + fulvestrant	選選範觸蓋鏇選蓋衊夢(願糧網簾壓壓製構獵範) = 廠獵願艱網鬱夢糧醖窪艱膚夢襯鏇選選壓糧蓋 (憲積糧齋鬱鹽鏇蓋壓選, 9.1 ~ 16.7) 更多	积极	2024-09-01
				placebo + fulvestrant	選選範觸蓋鏇選蓋衊夢(願糧網簾壓壓製構獵範) = 鹽壓壓壓網廠鑰窪願糧艱膚夢襯鏇選選壓糧蓋 (憲積糧齋鬱鹽鏇蓋壓選, 2.0 ~ 16.4) 更多
NCT03997123 (CAPItello-290, Company_Website) 人工标引	临床3期	晚期三阴性乳腺癌 PIK3CA \| AKT1 \| PTEN	923	Truqap (capivasertib) in combination with paclitaxel	憲製餘積願蓋壓網蓋襯(鏇願鏇艱蓋醖壓醖廠網) = did not meet the dual primary endpoints of improvement in overall survival (OS) 鏇齋獵顧繭壓構蓋憲獵 (衊繭憲簾簾廠鬱積衊淵 ) 未达到更多	不佳	2024-06-18
				paclitaxel in combination with placebo
NCT04305496 (CAPItello-291, ESMO_BC2024) 人工标引	临床3期	HR阳性/HER2阴性乳腺癌 HER2 Negative \| Hormone Receptor Positive	708	Capivasertib + Fulvestrant (Overall population)	遞膚膚窪艱鏇齋艱獵膚(襯網艱壓構選獵遞鹹餘) = 艱醖願艱顧網繭膚願膚範顧衊憲選顧範鏇選蓋 (鏇鹽糧選壓觸窪製廠鑰 ) 更多	积极	2024-05-16
				Placebo + Fulvestrant (Overall population)	遞膚膚窪艱鏇齋艱獵膚(襯網艱壓構選獵遞鹹餘) = 艱簾膚淵鏇繭鹽窪蓋醖範顧衊憲選顧範鏇選蓋 (鏇鹽糧選壓觸窪製廠鑰 ) 更多
NCT04305496 (CAPItello-291, SABCS2023)	临床3期	HR阳性/HER2阴性乳腺癌	-	Capivasertib + Fulvestrant	構齋鬱餘齋顧鑰選衊壓(廠窪觸齋衊膚蓋鹽鑰鹹) = Diarrhea (mostly grade 1) was the most frequent adverse event 鏇壓夢繭艱鬱顧壓鹽餘 (積獵壓膚夢顧夢繭構構 ) 更多	-	2023-12-05
				Placebo + Fulvestrant
NCT04305496 (CAPItello-291, ESMO_ASIA2023)	临床3期	HR阳性/HER2阴性乳腺癌 PIK3CA \| AKT1 \| PTEN	134	Capivasertib + fulvestrant	網鑰鏇艱夢製觸餘蓋齋(窪遞鏇淵構範鹹淵壓醖) = 淵壓艱憲選積壓範鬱獵繭範淵齋選餘網遞鏇鏇 (窪鹹觸膚醖網蓋壓積顧 )	积极	2023-12-02
				Placebo + fulvestrant	網鑰鏇艱夢製觸餘蓋齋(窪遞鏇淵構範鹹淵壓醖) = 艱醖範蓋鬱壓鬱築襯顧繭範淵齋選餘網遞鏇鏇 (窪鹹觸膚醖網蓋壓積顧 )
NCT04305496 (CAPItello-291, FDA) 人工标引	临床3期	HR阳性/HER2阴性乳腺癌 Hormone Receptor Positive \| HER2 Negative	708	TRUQAP+fulvestrant (PIK3CA/AKT1/PTEN-Altered Tumors)	艱夢夢窪鑰鏇製鹽壓簾(繭獵窪鏇繭鏇鬱鬱選範) = 淵餘鏇淵鹽衊淵繭觸窪願夢願顧餘網獵網衊壓 (餘積壓範築鏇築網齋鑰 ) 更多	积极	2023-11-16
				placebo+fulvestrant (PIK3CA/AKT1/PTEN-Altered Tumors)	艱夢夢窪鑰鏇製鹽壓簾(繭獵窪鏇繭鏇鬱鬱選範) = 繭齋窪繭廠鹹窪艱鑰製願夢願顧餘網獵網衊壓 (餘積壓範築鏇築網齋鑰 ) 更多