Survival results for AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan in TROPION-Breast01 did not achieve statistical significance versus chemotherapy

与化疗相比，阿斯利康和第一三共的达托帕单抗在TROPION-Breast01中的生存结果没有统计学意义

Trial previously met the dual primary

审判之前遇到了双重初选

endpoint of progression-free survival

无进展生存的终点

High-level results from the TROPION-Breast01 Phase III trial of datopotamab deruxtecan (Dato-DXd) compared to investigator’s choice of chemotherapy, which previously met the dual primary endpoint of progression-free survival (PFS), did not achieve statistical significance in the final overall survival (OS) analysis in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy..

与之前符合无进展生存期（PFS）双重主要终点的研究者选择的化疗相比，达托单抗-德鲁替康（Dato DXd）的TROPION-Breast01 III期临床试验的高水平结果在最终总生存期（OS）分析中未达到统计学显着性对于先前接受内分泌治疗和至少一种全身治疗的无法手术或转移性激素受体（HR）阳性，HER2低或阴性（IHC 0，IHC 1+或IHC 2+/ISH-）乳腺癌患者。。

This analysis follows the positive PFS results presented at the 2023 European Society for Medical Oncology Congress which showed datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement in PFS. An improvement in patient-reported outcomes was also seen.1 The PFS data and additional results for key secondary endpoints were published this month in the Journal of Clinical Oncology..

这项分析遵循了2023年欧洲医学肿瘤学会大会上提出的积极的PFS结果，该结果显示达托巴单抗deruxtecan在PFS方面表现出统计学上显着且临床上有意义的改善。患者报告的结果也有所改善。PFS数据和关键次要终点的其他结果本月发表在《临床肿瘤学杂志》上。。

The safety profile of datopotamab deruxtecan was consistent with that observed in the previous analysis including lower rates of Grade 3 or higher treatment-related adverse events compared to chemotherapy, and no new safety concerns identified. All grade interstitial lung disease (ILD) rates remained low with no new Grade 3 or higher ILD events observed..

达托单抗-德鲁替康的安全性与先前分析中观察到的一致，包括与化疗相比，3级或更高的治疗相关不良事件发生率较低，并且没有发现新的安全性问题。所有级别的间质性肺病（ILD）发生率仍然很低，没有观察到新的3级或更高的ILD事件。。

With multiple antibody drug conjugates (ADCs) approved during the course of the trial, including Enhertu (trastuzumab deruxtecan), subsequent treatment following patients’ disease progression or treatment discontinuation is likely to have affected survival results.

在试验过程中批准了多种抗体-药物偶联物（ADC），包括Enhertu（曲妥珠单抗-德鲁替康），患者疾病进展或停药后的后续治疗可能会影响生存结果。

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The metastatic HR-positive breast cancer treatment landscape has advanced remarkably in the last several years to the benefit of patients. Based on the TROPION-Breast01 results, there is evidence of the clinical value of datopotamab deruxtecan in this setting.

阿斯利康肿瘤研发执行副总裁苏珊·加尔布雷斯（SusanGalbraith）表示：“在过去几年中，转移性HR阳性乳腺癌治疗领域取得了显着进展，为患者带来了益处。根据TROPION-Breast01的结果，有证据表明达托巴-德鲁替康在这种情况下具有临床价值。

We will continue discussions with regulatory authorities and apply insights from these results to our clinical development programme for datopotamab deruxtecan in breast cancer.”.

我们将继续与监管机构进行讨论，并将这些结果的见解应用于我们的达托单抗-德鲁替康乳腺癌临床开发计划。”。

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “Datopotamab deruxtecan has previously shown a statistically significant progression-free survival benefit in TROPION-Breast01, a result supported by multiple meaningful secondary measures including patient-reported outcomes. We are proud to have brought forth a new standard of care for patients with metastatic breast cancer with Enhertu and we remain committed to making datopotamab deruxtecan another potential option for patients who can benefit.”.

Daiichi Sankyo研发全球负责人Ken Takeshita医学博士说：“达托单抗-德鲁替康之前在TROPION-Breast01中显示出统计学上显着的无进展生存获益，这一结果得到了包括患者报告结果在内的多种有意义的二级指标的支持。我们很自豪为患有Enhertu的转移性乳腺癌患者提供了新的护理标准，我们仍然致力于使达托单抗-德鲁替康成为可能受益的患者的另一种潜在选择。”。

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd ADC discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.

Datopotamab deruxtecan是由Daiichi Sankyo发现并由AstraZeneca和Daiichi Sankyo联合开发的一种专门设计的TROP2定向DXd ADC。

The data will be presented at a forthcoming medical meeting and shared with regulatory authorities currently reviewing applications for this indication.

这些数据将在即将举行的医疗会议上提交，并与目前正在审查该适应症申请的监管机构共享。

In addition to TROPION-Breast01, AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan alone and with immunotherapy as treatment for patients with triple-negative or HR-low, HER2-negative breast cancers in the TROPION-Breast02, TROPION-Breast03, TROPION-Breast04 and TROPION-Breast05 Phase III trials..

除TROPION-Breast01外，阿斯利康和第一三共正在TROPION-Breast02、TROPION-Breast03、TROPION-Breast04和TROPION-Breast05 III期试验中评估单独使用达托巴单抗和免疫疗法治疗三阴性或HR低、HER2阴性乳腺癌患者。。

Notes

注意事项

​HR-positive breast cancer

​HR阳性乳腺癌

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.2 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.2 While survival rates are high for those diagnosed with early breast cancer, less than 35% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.3.

乳腺癌是世界上第二大最常见的癌症，也是全球癌症相关死亡的主要原因之一。2022年诊断出200多万例乳腺癌病例，全球死亡人数超过665000人。2虽然早期乳腺癌患者的生存率很高，但诊断为转移性疾病或进展为转移性疾病的患者中，只有不到35%的患者预计在诊断后能活五年。

Approximately 70% of diagnosed cases are considered what has been historically called HR-positive, HER2-negative breast cancer (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).3 Endocrine therapies are widely given consecutively in the early lines of treatment for HR-positive metastatic breast cancer; however, after two lines of treatment, further efficacy from endocrine therapy is often limited.4 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.4-7.

大约70%的诊断病例被认为是历史上所谓的HR阳性，HER2阴性乳腺癌（以IHC 0，IHC 1+或IHC 2+/ISH的HER2评分来衡量）[3]。内分泌治疗在HR阳性转移性乳腺癌的早期治疗中被广泛应用；然而，经过两种治疗方案后，内分泌治疗的进一步疗效往往有限[4]。内分泌治疗后目前的护理标准是化疗，这与不良反应率和预后相关[4-7]。

TROP2 is a protein broadly expressed in HR-positive, HER2-negative breast cancer and is associated with increased tumour progression and poor survival.8,9

TROP2是一种在HR阳性，HER2阴性乳腺癌中广泛表达的蛋白质，与肿瘤进展增加和生存率低有关。8,9

TROPION-Breast01

TROPION-Breast01

​TROPION-Breast01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable or metastatic HR-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease..

​TROPION-BRAST01是一项全球性，随机，多中心，开放标签的III期临床试验，评估达托单抗-德鲁替康（6.0mg/kg）与研究者选择单药化疗（依立布林，卡培他滨，长春瑞滨或吉西他滨）的疗效和安全性。对于不可切除或转移性HR阳性，HER2低或阴性（IHC 0，IHC 1+或IHC 2+/ISH-）乳腺癌的成年患者，根据研究者的评估，这些患者已经进展并且不适合内分泌治疗，并且已经接受了至少一种针对不可切除或转移性疾病的额外全身治疗。。

Following disease progression or discontinuation of datopotamab deruxtecan or chemotherapy, patients had the option to receive subsequent treatment at the discretion of their physician. Crossover between trial arms was not permitted.

在疾病进展或停用达托单抗德鲁替康或化疗后，患者可以选择由医生自行决定接受后续治疗。试验组之间的交叉是不允许的。

The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety.

TROPION-Breast01的双重主要终点是通过盲法独立中央审查和OS评估的PFS。主要次要终点包括客观缓解率，缓解持续时间，研究者评估的PFS，疾病控制率，首次后续治疗的时间和安全性。

TROPION-Breast01 enrolled more than 700 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

TROPION-Breast01在非洲，亚洲，欧洲，北美和南美招募了700多名患者。有关更多信息，请访问ClinicalTrials.gov。

​​Datopotamab deruxtecan (Dato-DXd)

达托帕单抗（DXd数据）

​Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform.

​Datopotamab deruxtecan（Dato DXd）是一种研究性TROP2指导的ADC。datopotamab deruxtecan使用Daiichi Sankyo专有的DXd ADC技术设计，是Daiichi Sankyo肿瘤学管道中的六个DXd ADC之一，也是阿斯利康ADC科学平台中最先进的程序之一。

Datopotamab deruxtecan is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers..

Datopotamab deruxtecan由与札幌医科大学合作开发的人源化抗TROP2 IgG1单克隆抗体组成，通过基于四肽的可切割接头连接到许多拓扑异构酶I抑制剂有效载荷（exatecan衍生物DXd）。。

​​A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer (TNBC) and HR-positive, HER2-negative breast cancer. The programme includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings..

​​一项全面的全球临床开发计划正在进行中，有20多项试验评估了达托巴单抗deruxtecan在多种癌症中的疗效和安全性，包括NSCLC，三阴性乳腺癌（TNBC）和HR阳性，HER2阴性乳腺癌。该计划包括7项肺癌III期临床试验和5项乳腺癌III期临床试验，评估达托单抗-德鲁替康作为单一疗法以及在各种情况下与其他抗癌治疗相结合。。

​​Daiichi Sankyo collaboration

​​第一三共合作

​AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan..

​阿斯利康（AstraZeneca）和第一三共（Daiichi Sankyo）于2019年3月达成全球合作，共同开发Enhertu，并于2020年7月将其商业化，但在日本，第一三共（Daiichi Sankyo）对每个ADC拥有专有权。Daiichi Sankyo负责Enhertu和datopotamab deruxtecan的制造和供应。。

​​AstraZeneca in breast cancer

​​阿斯利康治疗乳腺癌

​Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death..

​在对乳腺癌生物学越来越了解的推动下，阿斯利康开始挑战并重新定义当前乳腺癌分类和治疗的临床范例，以便为有需要的患者提供更有效的治疗方法-大胆的雄心壮志是有一天消除乳腺癌作为死亡原因。。

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

阿斯利康在开发中拥有一系列经过批准且有前景的化合物，这些化合物利用不同的作用机制来解决生物学上多样化的乳腺癌肿瘤环境。

With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

使用HER2导向的ADC Enhertu（曲妥珠单抗-德鲁替康），阿斯利康和第一三共旨在改善先前治疗的HER2阳性和HER2低转移性乳腺癌的预后，并正在探索其在早期治疗和新乳腺癌环境中的潜力。

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap, and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting..

在HR阳性乳腺癌中，阿斯利康继续使用基础药物Faslodex和Zoladex（戈舍瑞林）改善预后，旨在用一流的AKT抑制剂Truqap和下一代SERD以及潜在的新药卡米西坦重塑HR阳性空间。阿斯利康还与第一三共合作，在这种情况下探索TROP2指导的ADC datopotamab deruxtecan的潜力。。

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease..

PARP抑制剂Lynparza（olaparib）是一种靶向治疗选择，已在具有遗传性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MSD（美国和加拿大的默克公司）继续在这些环境中研究林帕扎，并探索其在早期疾病中的潜力。。

To bring much-needed treatment options to patients with TNBC, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu..

为了给TNBC（一种侵袭性乳腺癌）患者带来急需的治疗选择，阿斯利康正在评估单独使用达托巴单抗和联合免疫治疗Imfinzi（durvalumab），Truqap联合化疗以及Imfinzi联合其他肿瘤药物（包括Lynparza和Enhertu）的潜力。。

​​AstraZeneca in oncology

​​阿斯利康肿瘤学

​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.

​阿斯利康（AstraZeneca）正在领导一场肿瘤学革命，致力于为各种形式的癌症提供治疗，遵循科学理解癌症及其复杂性，发现、开发并向患者提供改变生命的药物。

​​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.

​​该公司专注于一些最具挑战性的癌症。正是通过不断的创新，阿斯利康建立了行业内最多样化的投资组合和渠道之一，有可能促进医学实践的变化并改变患者的体验。

​​AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

​​阿斯利康的愿景是重新定义癌症护理，并有一天消除癌症作为死亡原因。

​​AstraZeneca

​​阿斯利康

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.

阿斯利康（LSE/STO/Nasdaq:AZN）是一家全球科学领先的生物制药公司，专注于肿瘤学，罕见病和生物制药（包括心血管，肾脏和代谢以及呼吸和免疫学）处方药的发现，开发和商业化。

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..

阿斯利康的创新药物总部位于英国剑桥，在125多个国家销售，全球数百万患者使用。请访问astrazeneca.com并在社交媒体@astrazeneca上关注该公司。。

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​​联系人

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References

参考文献

1. Pernas S, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer: Patient-reported outcomes (PROs) from the TROPION-Breast01 study. Presented at: ASCO Congress 2024; 31 May - 4 June, 2024; Chicago, IL.

1.Pernas S等人。达托单抗-德鲁替康（Dato-DXd）与先前治疗的不可手术或转移性激素受体阳性，HER2阴性（HR+/HER2-）乳腺癌的化疗：来自TROPION-BRAST01研究的患者报告结果（PRO）。出席：ASCO 2024年大会；；伊利诺伊州芝加哥。

Abstract 1006..

摘要1006。。

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3、国家癌症研究所。监测、流行病学和最终结果计划。https://seer.cancer.gov/statfacts/html/breast-subtypes.html.2024年8月访问

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。柳叶刀。2011年；377:914-923年。

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6.Yuan P等人。甲磺酸依瑞布林与长春瑞滨治疗局部复发或转移性乳腺癌的随机临床试验。Eur J癌症。；112:57-65。

7. Jerusalem G, et al. Everolimus Plus Exemestane vs Everolimus or Capecitabine Monotherapy for Estrogen Receptor–Positive, HER2-Negative Advanced Breast Cancer. JAMA Oncol. 2018;4(10):1367–1374.

7.Jerusalem G等人。依维莫司联合依西美坦与依维莫司或卡培他滨单药治疗雌激素受体阳性，HER2阴性的晚期乳腺癌。JAMA Oncol。2018年；4（10）：1367-1374。

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9. Vidula N, et al. Trophoblast Cell Surface Antigen 2 gene (TACSTD2) expression in primary breast cancer. Breast Cancer Res Treat. 2022 Aug;194(3):569-575.

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Adrian Kemp

阿德里安·肯普

Company Secretary

公司秘书

AstraZeneca PLC

阿斯利康