Astex Pharmaceuticals, Inc.

AstraZeneca is discontinuing the CAPItello-280 Phase III trial evaluating the efficacy and safety of Truqap (capivasertib) in combination with docetaxel and androgen-deprivation therapy (ADT) compared to docetaxel and ADT with placebo in patients with metastatic castration-resistant prostate cancer (mCRPC). This decision is based on the recommendation of the Independent Data Monitoring Committee (IDMC) following their review of data from a pre-specified interim analysis, which concluded that the Truqap combination was unlikely to meet the dual primary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) versus the comparator arm upon trial completion. The safety profile for Truqap was consistent with previous trials. The Company will work with investigators to ensure the necessary follow up with patients. Data from the trial will inform ongoing research. Notes Prostate cancer Prostate cancer is the second most prevalent cancer in men and the fifth leading cause of male cancer death globally, with an incidence of more than 1.4 million and over 397,000 deaths in 2022.1 Metastatic prostate cancer is associated with a significant mortality rate, with only one third of patients surviving five years after diagnosis.2 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.3 Metastatic castration-resistant prostate cancer Approximately 10-20% of men with advanced prostate cancer will develop castration-resistant prostate cancer within five years.4 In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.3 At least 84% of these men will have metastases at the time of CRPC diagnosis and, of those patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.4 Approximately half of patients with mCRPC may receive only one line of active treatment, and those that go on to receive further treatment often have diminishing benefit of subsequent therapies.5-6 Despite the advances in mCRPC treatment with taxane and new hormonal agent treatments, there is high unmet need in this population.4,7,8 CAPItello-280 CAPItello-280 is a Phase III, double-blind, randomised trial evaluating the efficacy and safety of Truqap in combination with docetaxel and ADT compared to docetaxel and ADT in combination with placebo in patients with mCRPC. The global trial enrolled 1,033 adult patients with histologically confirmed prostate adenocarcinoma with evidence of mCRPC with progression of disease despite ADT. The dual primary endpoints of the CAPItello-280 trial are rPFS as assessed by investigator and OS in the overall trial population. Key secondary endpoints include OS and rPFS as assessed by investigator in patients with mCRPC and PTEN-deficient tumours, OS and rPFS as assessed by investigator in patients with mCRPC and PTEN-proficient tumours, time to pain progression (TTPP) in the overall trial population and time to first symptomatic skeletal-related event (SSRE) in the overall trial population. Truqap Truqap is a first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3). Truqap 400mg is administered twice daily according to an intermittent dosing schedule of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition. Truqap in combination with Faslodex (fulvestrant) is approved in the US, EU, Japan, China and several other countries for the treatment of adult patients with HR-positive (or estrogen receptor-positive), HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN) following recurrence or progression on or after an endocrine-based regimen based on the results from the CAPItello-291 trial. Truqap is also approved in Australia for the treatment of adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer following recurrence or progression on or after an endocrine based regimen based on these trial results. Truqap is being evaluated in ongoing Phase III trials for the treatment of breast and prostate cancers. Truqap was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited). AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here References Adrian Kemp Company Secretary AstraZeneca PLC Oncology Corporate and financial

In return for the licenses, Astex will receive 19% of Mosaic Therapeutics’ equity, with a further 3% to follow if milestones are hit.\n Mosaic Therapeutics has secured the latest pieces in its combination medicine strategy by licensing two clinical stage tumor drugs from fellow British biotech Astex Pharmaceuticals.The small molecules in question are ASTX029, an ERK1/2 inhibitor that has completed a phase 2 study, and ASTX295 an MDM2 antagonist that has undergone a phase 1 trial. Both candidates have demonstrated “single-agent activity as monotherapies, enabling use in combination therapies,” Mosaic explained in an April 24 release.In return for the licenses, Astex—which is owned by Otsuka Pharmaceutical—will receive 19% of Mosaic’s equity, with a further 3% to follow if milestones are hit.Cambridge, U.K.-based Mosaic secured a $28 million series A two years ago to fund its ambition to “resolve cancer’s complexity to power new treatments for patients.” In practice, this means combing through large datasets to identify combinations of oncology drugs that could increase their effectiveness in biomarker-defined patient populations.This morning’s deal “significantly accelerates Mosaic’s development path,” the biotech\'s chair Edward Hodgkin said in the April 24 release, meaning the company now expects to launch its first clinical study of a combination treatment next year. “The in-licensing of these two clinical stage assets provides a step change in our development pipeline, allowing Mosaic to progress targeted drug combinations in novel biomarker-defined settings and enabling the delivery of precision medicines for patients who currently have few therapeutic options,” added Hodgkin, who is also managing partner of Mosaic’s backer Syncona Investment Management.Astex, which like Mosaic is based in Cambridge in England, has a strong track record of working with Big Pharma in the past, including collaborating with the Novartis Institutes for BioMedical Research on breast cancer med Kisqali and AstraZeneca on its breast cancer treatment Truqap in the mid-2000s. More recently, the biotech secured a 2023 deal with Merck & Co.“We recognise the significance of Mosaic’s platform, which has identified these two assets as anchor components of a pipeline of potential combination products,” Astex’s CEO and co-founder Harren Jhoti, Ph.D., said in the release. “Both drug targets are well-characterised drivers of many cancers, and we are excited to be working with the experienced team at Mosaic to expand the Company’s pipeline in combination therapies with high unmet medical need.”

首个且唯一*在华获批、用于特定生物标志物（PIK3CA、AKT1 或 PTEN）改变的乳腺癌患者的AKT抑制剂此次获批基于CAPItello-291全球研究，其结果显示在生物标志物改变人群中，该药物联合氟维司群相较氟维司群单药可将疾病进展或死亡风险降低50%重磅发布2025年4月22日，上海——阿斯利康今日宣布，中国国家药品监督管理局于2025年4月15日正式批准荃科得®（英文商品名: Truqap®，通用名：卡匹色替片）联合氟维司群用于转移性阶段至少接受过一种内分泌治疗后疾病进展，或在辅助治疗期间或完成辅助治疗后12个月内复发的激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性且伴有一种或多种PIK3CA/AKT1/PTEN改变的局部晚期或转移性乳腺癌成人患者。此次在华获批是基于早前发表在《新英格兰医学杂志》上的CAPItello-291全球III期研究的积极结果1，2023年欧洲肿瘤内科学会亚洲年会（ESMO Asia）上公布的中国队列的积极结果与全球研究结果一致，也支持了本次获批。2在该试验的全球人群中，69%的患者曾接受过细胞周期蛋白依赖性激酶 (CDK) 4/6 抑制剂治疗，研究结果显示，对于携带PI3K/AKT通路中生物标志物改变的患者，卡匹色替联合氟维司群相较于氟维司群单药治疗可将疾病进展或死亡风险降低50%（风险比0.50，95%置信区间0.38-0.65；p=<0.001；中位无进展生存期 (PFS) 为7.3个月对比3.1个月）。1在中国人群中，相较于氟维司群单药治疗，卡匹色替联合氟维司群可将携带PIK3CA、AKT1或PTEN基因改变患者的疾病进展或死亡风险降低59%（风险比0.41；中位PFS为5.7个月对比1.9个月）。2乳腺癌是中国女性最高发的恶性肿瘤之一，仅2022年确诊病例就超过35万例，并造成约75,000例患者死亡。3在全球范围内，HR阳性乳腺癌（表达雌激素和/或孕激素受体）是最常见的乳腺癌亚型， 70%的乳腺癌被认为是HR阳性、HER2阴性。4内分泌治疗联合细胞周期蛋白依赖性激酶 (CDK) 4/6 抑制剂在晚期乳腺癌患者的初始治疗中被广泛使用，但肿瘤仍会对这些疗法产生耐药，尤其是当肿瘤携带PIK3CA、AKT1或PTEN改变时，因此亟需更多基于内分泌治疗的联合用药方案以优化内分泌治疗的获益时间和疗效。5全球数据显示，约 50% 的HR阳性晚期乳腺癌患者携带PIK3CA、AKT1或PTEN基因的改变。6-8在中国人群中，约57%的HR阳性、HER2阴性乳腺癌患者携带PIK3CA、AKT1或PTEN改变，其中携带PTEN或AKT1改变的比例分别高达8.4%和7.7%。9胡夕春 教授复旦大学附属肿瘤医院大内科首席，ESMO 国际乳腺癌专家委员会委员，CAPItello-291中国牵头研究者晚期HR阳性乳腺癌患者往往在一线内分泌疗法中出现疾病进展或耐药。很高兴看到此次获批为伴有PIK3CA、AKT1或PTEN基因改变的晚期HR阳性乳腺癌患者带来全新治疗选择，有望帮助患者延缓疾病进程并延长生存时间，同时也彰显了乳腺癌精准诊疗的重要性。何静 博士阿斯利康全球高级副总裁，全球研发中国负责人乳腺癌严重威胁中国女性的生命健康，患者亟需创新治疗方案的需求尚未被满足。卡匹色替是首个且唯一在中国获批用于PIK3CA/AKT1/PTEN改变的乳腺癌患者的AKT抑制剂，此次获批充分彰显了我们药物的创新价值, 未来我们将继续借助自身研发实力和管线布局，倾力攻克乳腺癌这一致死疾病。关冬梅 女士阿斯利康中国肿瘤业务总经理卡匹色替有望延长目前被广泛使用的内分泌治疗的获益，并帮助HR阳性晚期乳腺癌患者延缓疾病进展，它的获批是阿斯利康中国持续探索乳腺癌领域的又一重要里程碑。阿斯利康与健康中国2030癌症防治目标同心同行，我们期待能将更多全球创新肿瘤药物带给广大中国患者，并为“健康中国2030”宏伟目标的达成贡献力量。在CAPItello-291试验中，卡匹色替联合氟维司群的安全性与此前开展的联合用药试验中观察到的结果基本一致。1基于CAPItello-291试验结果，目前卡匹色替已在美国、欧盟、日本等其他国家和地区获批用于治疗HR阳性晚期乳腺癌患者。关于HR阳性乳腺癌乳腺癌是全球第二高发的癌症，也是全球癌症相关死亡的主要原因之一。10 2022年，全球超过 200 多万名患者被诊断为乳腺癌，有近665,000 名患者死亡。10HR 阳性乳腺癌细胞的生长通常由雌激素受体驱动，内分泌疗法被广泛用作ER驱动的晚期乳腺癌的一线治疗，并通常与 CDK4/6 抑制剂联合使用。5,11,12然而，许多晚期乳腺癌患者会对 CDK4/6 抑制剂和目前的内分泌疗法产生耐药性。11一旦出现这种情况，治疗选择就会相对有限（化疗是目前的标准治疗方法），并且生存率较低，预计只有35%的患者在诊断后能够存活五年以上。4,11,13优化内分泌治疗并克服耐药，以使患者能够继续从内分泌治疗中获益，同时为那些不太可能受益的患者寻找新的治疗方法，是目前乳腺癌研究的活跃关注领域。关于CAPItello-291CAPItello-291是一项III期、双盲、随机试验，旨在评估卡匹色替联合氟维司群对比安慰剂联合氟维司群在局部晚期（不可手术）或转移性激素受体阳性、HER2低表达或阴性（免疫组化[IHC] 0或1+，或IHC 2+/原位杂交[ISH]阴性）乳腺癌患者中的疗效。这项全球研究招募了708名患有组织学确认的激素受体阳性、HER2低表达或阴性乳腺癌的成年患者。这些患者的疾病在芳香化酶抑制剂治疗期间或之后复发或进展，可能已经接受了CDK4/6抑制剂治疗及晚期一线化疗。该试验具有双重主要终点：总体人群中的PFS和PI3K/AKT通路改变（PIK3CA、AKT1或PTEN基因改变）患者人群的PFS。本研究纳入约40%的通路改变人群，近 70% 的患者曾使用过 CDK4/6 抑制剂。该研究的中国队列以与全球研究相同的入排标准招募了134 名来自中国大陆和中国台湾地区的成年患者。在该队列中，约35%的患者的肿瘤携带PIK3CA、AKT1或PTEN改变，约40%的患者曾接受过CDK4/6抑制剂治疗。关于荃科得®荃科得®（卡匹色替）是一款first-in-class高效的三磷酸腺苷(ATP)竞争性抑制剂，可抑制所有三种AKT异构体（AKT1/2/3）。根据早期试验中的耐受性和靶点抑制程度进行给药方案的选择，卡匹色替每天两次，每次400mg，按照四天用药、三天停药的间歇剂量方案给药。根据 CAPItello-291 试验的结果，卡匹色替已在美国、欧盟、日本、中国及其他几个国家获得批准，用于治疗 HR 阳性、HER2 阴性局部晚期或转移性乳腺癌成人患者，这些患者在接受内分泌治疗期间或之后出现复发或进展，且具有一种或多种生物标志物改变（PIK3CA、AKT1 或 PTEN）。根据这些试验结果，卡匹色替还在澳大利亚获得批准，用于治疗在接受内分泌治疗期间或之后出现复发或进展的 HR 阳性、HER2 阴性局部晚期或转移性乳腺癌成人患者。卡匹色替目前正在开展多项III期临床试验，以评估其单独应用或者与既定治疗方案联合应用在乳腺癌(CAPItello-292)和前列腺癌(CAPItello-280及CAPItello-281)中的治疗效果。卡匹色替是阿斯利康与Astex Therapeutics 合作（以及与伦敦癌症研究所和癌症研究技术有限公司的合作）之后开发的。关于芙仕得®芙仕得®（氟维司群）是一种内分泌疗法，适用于在抗雌激素辅助治疗后或治疗过程中复发的，或是在抗雌激素治疗中进展的绝经后雌激素受体阳性的局部晚期或转移性乳腺癌。在美国、欧盟、中国和日本，氟维司群还被批准与CDK4/6抑制剂联合使用，用于治疗HR阳性、HER2阴性的晚期或转移性乳腺癌女性患者，这些患者在接受内分泌治疗后出现进展。氟维司群代表了一种激素治疗方法，通过阻断和降解雌激素受体（疾病进展的关键驱动因素）来帮助减缓肿瘤的生长。氟维司群被批准作为单一疗法或与包括CDK4/6和PI3K抑制剂在内的各类药物联合治疗HR阳性晚期乳腺癌患者，并且正在评估与其他药物的联合使用。关于阿斯利康在乳腺癌领域的研究在对乳腺癌生物学认识不断深化的驱动下，阿斯利康开始挑战并重新定义当前的乳腺癌分型及临床治疗模式，以为有需要的患者提供更为精准而有效的治疗方案。阿斯利康雄心勃勃，希望有朝一日可以消除乳腺癌这一致死病因。阿斯利康研发了一系列已获批或有望获批的药物，通过多种机制应对乳腺癌肿瘤微环境的生物多样性。凭借靶向HER2的抗体偶联药物——优赫得（德曲妥珠单抗），阿斯利康和第一三共致力于改善先前接受过治疗的HER2阳性、HER2低表达与HER2超低表达转移性乳腺癌患者的预后，并正在探索其在更早线的治疗和其他乳腺癌治疗阶段中的潜力。在HR阳性乳腺癌中，阿斯利康继续通过基石药物芙仕得 (氟维司群) 和诺雷得 (戈舍瑞林) 改善预后，并旨在通过first-in-class的AKT抑制剂荃科得 (卡匹色替)、靶向Trop2的ADC药物Datroway (datopotamab deruxtecan) 以及新一代口服SERD camizestrant重塑HR阳性乳腺癌的治疗。PARP抑制剂利普卓（奥拉帕利）是一种靶向治疗药物，已在遗传性BRCA突变的早期和转移性乳腺癌患者中进行了研究。阿斯利康与默沙东（默沙东是美国新泽西州罗威市默克公司的公司商号）将继续利普卓在这些领域的相关研究，并探索其在疾病早期治疗中的潜力。阿斯利康还在探索Saruparib（一种强效的PARP1选择性抑制剂）与camizestrant联合治疗BRCA突变、HR阳性、HER2阴性晚期乳腺癌的有效性和安全性。为了给三阴性乳腺癌（一种侵袭性乳腺癌）患者提供急需的治疗选择，阿斯利康正在评估 Datroway单独使用或与免疫药物英飞凡(度伐利尤单抗)联合使用的潜在效果。关于阿斯利康在肿瘤领域的研究阿斯利康正引领着肿瘤领域的一场革命，致力于提供多元化的肿瘤治疗方案，以科学探索肿瘤领域的复杂性，发现、研发并向患者提供改变生命的药物。阿斯利康专注于最具挑战性的肿瘤疾病，通过持续不断的创新，阿斯利康已经建立了行业领先的多元化的产品组合和管线，持续推动医疗实践变革，改变患者体验。阿斯利康以期重新定义癌症治疗并在未来攻克癌症。声明：* 截至2025年4月22日，在中国大陆是唯一本文涉及尚未在中国大陆获批的产品或者适应症，阿斯利康不推荐任何未被批准的药品使用。内容来源：新闻稿 (内部审批号:CN-158608）参考文献（滑动查看更多）1.Turner N, et al. Capivasertib in Hormone Receptor–Positive Advanced Breast Cancer. NEJM. 2023; 388:2058–70.2.Xichun H, et al. Capivasertib + fulvestrant for patients with aromatase inhibitor resistant HR positive/HER2 negative advanced breast cancer: Phase 3 CAPItello 291 trial Chinese cohort. Annals of Oncology (2023) 34 (suppl_4): S1485-S1493. 10.1016/annonc/annonc1376.3.Zhonghua Z, et al. Breast Cancer Expert Committee of National Cancer Quality Control Center. Chinese Journal of Oncology. 2024; 46,12: 1079-1106.4.National Cancer Institute. Surveillance, Epidemiology and End Results Program. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed April 2025.5.Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer. 2020; 10.7150/jca.48944.6.Howell S J, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION). J Clin Oncol. 2022; 23:851-64.7.Hortobagyi G N, et al. Correlative Analysis of Genetic Alterations and Everolimus Benefit in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From BOLERO-2. J Clin Oncol. 2016; 34:419-26.8.Millis S Z, et al. Landscape of phosphatidylinositol-3-kinase pathway alterations across 19784 diverse solid tumors. JAMA Oncol. 2016;2(12):1565-73.9.Ziang Li, et al. 2024 SABCS. P3-10-13: A Comprehensive Analysis of Dysregulation in the PTEN/PI3K/AKT Pathway in Breast Cancer Among the Chinese Population10.American Cancer Society. Key Statistics for Breast Cancer. Available at: https://www.cancer.org/cancer/breast-cancer/about/how-common-is-breast-cancer.html. Accessed April 2025.11.Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor–positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities. Clin Cancer Res. 2022; 28(5):821-30.12.Scabia V, et al. Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor. Nat Commun. 2022; 10.1038/s41467-022-30898-0.13.National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology (NCCN Guidelines). Available at: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419. Accessed April 2025.