AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan demonstrated meaningfully greater magnitude of progression-free survival benefit in patients with this biomarker

阿斯利康（AstraZeneca）和第一三共（Daiichi Sankyo）的达托帕单抗（datopotamab deruxtecan）在这种生物标志物患者中显示出更大程度的无进展生存获益

AstraZeneca and Roche Tissue Diagnostics are collaborating to co-develop and commercialise the TROP2-QCS biomarker companion diagnostic

阿斯利康和罗氏组织诊断公司正在合作共同开发TROP2-QCS生物标志物伴侣诊断并将其商业化

Results from an exploratory analysis of the TROPION-Lung01 Phase III trial showed TROP2 as measured by AstraZeneca’s proprietary computational pathology platform, quantitative continuous scoring (QCS), was predictive of clinical outcomes in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who were treated with datopotamab deruxtecan (Dato-DXd).

对TROPION-Lung01 III期临床试验的探索性分析结果显示，通过阿斯利康专有的计算病理学平台定量连续评分（QCS）测量的TROP2可预测晚期或转移性非小细胞肺癌（NSCLC）患者的临床结果用达托巴单抗-德鲁替康（Dato-DXd）治疗。

In patients with TROP2-QCS biomarker positive tumours, datopotamab deruxtecan demonstrated a meaningfully greater magnitude of efficacy versus docetaxel than in the overall trial population..

在TROP2-QCS生物标志物阳性肿瘤患者中，达托单抗deruxtecan与多西紫杉醇相比，其疗效显着高于总体试验人群。。

These results will be featured in a Presidential Symposium (PL02.11) at the IASLC 2024 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer.

这些结果将在国际肺癌研究协会主办的IASLC 2024年世界肺癌会议（WCLC）的总统研讨会（PL02.11）上发表。

TROP2 is a protein broadly expressed in NSCLC on the surface of and inside tumour cells.1,2 When assessed using conventional immunohistochemistry (IHC)-based pathology, TROP2 expression has not been predictive of patient responses to TROP2-directed antibody drug conjugates (ADC).3,4 QCS is a fully supervised computational pathology platform, developed by AstraZeneca, that analyses digitised images of patient tissue samples and precisely quantifies targets, like TROP2, on and inside a tumour cell..

TROP2是一种在肿瘤细胞表面和内部的NSCLC中广泛表达的蛋白质。1,2当使用基于常规免疫组织化学（IHC）的病理学进行评估时，TROP2的表达并不能预测患者对TROP2定向抗体-药物偶联物（ADC）的反应。3,4 QCS是由阿斯利康开发的一个完全监督的计算病理学平台，它分析患者组织样本的数字化图像，并精确量化肿瘤细胞上和内部的靶标，如TROP2。。

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。

In this analysis, QCS was used to analyse tissue samples collected from patients in TROPION-Lung01. This produced a normalised membrane ratio for each tumour cell in each sample. Patients’ tumours were considered TROP2-QCS biomarker positive if the majority (≥75%) of tumour cells exhibited a ratio below a predetermined value (≤0.56), indicating a greater proportion of TROP2 in the cytoplasm..

在此分析中，QCS用于分析从TROPION-Lung01患者收集的组织样本。这为每个样品中的每个肿瘤细胞产生了标准化的膜比率。如果大多数（≥75%）肿瘤细胞的比例低于预定值（≤0.56），表明TROP2在细胞质中的比例更高，则患者的肿瘤被认为是TROP2-QCS生物标志物阳性。。

The analysis showed a greater proportion of patients with nonsquamous NSCLC were considered TROP2-QCS biomarker positive than those with squamous NSCLC (66% versus 44%, respectively). The threshold for biomarker positivity was optimised for progression-free survival (PFS) in the subgroup of patients with nonsquamous NSCLC without actionable genomic alterations because it represents a population with significant unmet medical need and without actionable biomarkers..

分析显示，非鳞状NSCLC患者中TROP2-QCS生物标志物阳性的比例高于鳞状NSCLC患者（分别为66%和44%）。生物标志物阳性的阈值针对非鳞状细胞癌患者亚组的无进展生存期（PFS）进行了优化，没有可行的基因组改变，因为它代表了一个具有显着未满足的医疗需求且没有可行的生物标志物的人群。。

In patients with TROP2-QCS biomarker positive tumours (60% of the biomarker evaluable population including patients with nonsquamous and squamous NSCLC), datopotamab deruxtecan reduced the risk of disease progression or death by 43% versus docetaxel (median PFS of 6.9 versus 4.1 months; hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.41-0.79)..

在TROP2-QCS生物标志物阳性肿瘤患者（60%的生物标志物可评估人群，包括非鳞状和鳞状NSCLC患者）中，与多西紫杉醇相比，达托单抗德鲁替康将疾病进展或死亡风险降低了43%（中位PFS为6.9比4.1个月；风险比[HR]0.57；95%置信区间[CI]0.41-0.79）。。

By comparison, in the primary analysis of the overall trial population, datopotamab deruxtecan reduced the risk of disease progression or death by 25% versus docetaxel (PFS of 4.4 versus 3.7 months; HR 0.75; 95% CI 0.62-0.91; p=0.004) as presented at the 2023 European Society for Medical Oncology Congress.5.

相比之下，在对总体试验人群的初步分析中，达托单抗-德鲁替康与多西他赛相比，疾病进展或死亡风险降低了25%（PFS为4.4比3.7个月；HR为0.75；95%CI为0.62-0.91；p=0.004），如2023年欧洲医学肿瘤学会大会所示。

In the subgroup of patients with nonsquamous NSCLC without actionable genomic alterations and with TROP2-QCS biomarker positive tumours, datopotamab deruxtecan reduced the risk of disease progression or death by 48% (PFS of 7.2 versus 4.1 months; HR 0.52; 95% CI 0.35-0.78).

在无可行基因组改变且TROP2-QCS生物标志物阳性肿瘤的非鳞状NSCLC患者亚组中，达托单抗-德鲁替康将疾病进展或死亡风险降低48%（PFS为7.2比4.1个月；HR 0.52；95%CI 0.35-0.78）。

Marina Garassino, MD, The University of Chicago, Professor of Medicine and investigator in the trial, said: “TROP2 is broadly expressed on solid tumour cells, including non-small cell lung cancer, but it has yet to be established as a predictive biomarker for any TROP2-directed antibody drug conjugate.

芝加哥大学医学博士、医学教授兼试验研究者Marina Garassino说：“TROP2在实体瘤细胞（包括非小细胞肺癌）上广泛表达，但尚未被确定为任何TROP2定向抗体-药物偶联物的预测性生物标志物。

We have shown with this analysis that the more precise quantitative measurement of TROP2 on and inside tumour cells, enabled by AstraZeneca’s computational pathology platform, can identify which patients with non-small cell lung cancer are most likely to benefit from treatment with datopotamab deruxtecan.”.

我们已经通过这项分析表明，通过阿斯利康的计算病理学平台，可以更精确地定量测量肿瘤细胞上和肿瘤细胞内的TROP2，可以确定哪些非小细胞肺癌患者最有可能从达托单抗-德鲁替康治疗中受益。”。

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “This analysis demonstrates the power of our computational pathology platform to discover new predictive biomarkers and substantially improve patient selection for datopotamab deruxtecan. It also has great potential to help more precisely select patients across our broader antibody drug conjugate portfolio.

阿斯利康肿瘤研发执行副总裁苏珊·加尔布雷斯（SusanGalbraith）表示：“这项分析证明了我们的计算病理学平台能够发现新的预测性生物标志物，并大大改善达托单抗-德鲁替康的患者选择。它还具有很大的潜力，可以帮助我们在更广泛的抗体-药物偶联物组合中更精确地选择患者。

​We are excited to extend our collaboration with Roche Tissue Diagnostics with the aim of validating this exploratory approach for TROP2, developing the companion diagnostic and bringing it to the clinic as quickly as possible.”.

​我们很高兴扩展与罗氏组织诊断公司的合作，旨在验证TROP2的这种探索性方法，开发配套诊断并尽快将其带到临床。”。

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “The results from the QCS analysis support the potential of TROP2, as measured by quantitative continuous scoring, as a predictive biomarker for datopotamab deruxtecan and begin to answer the question of why certain patients with non-small cell lung cancer respond better to treatment.

Daiichi Sankyo全球研发主管Ken Takeshita医学博士说：“QCS分析的结果支持TROP2作为达托单抗-德鲁替康预测生物标志物的潜力，并开始回答为什么某些非小细胞肺癌患者对治疗反应更好的问题。

These insights are critical to advancing our understanding of how we can more precisely identify patients with non-small cell lung cancer who may benefit from treatment with our TROP2-directed antibody drug conjugate.”.

这些见解对于增进我们对如何更准确地识别可能受益于TROP2定向抗体-药物偶联物治疗的非小细胞肺癌患者的理解至关重要。”。

In the biomarker evaluable population, no new safety concerns were identified and rates of Grade 3 or higher treatment-related adverse events (TRAE) were similar regardless of TROP2 status. In patients with TROP2-QCS biomarker positive tumours, Grade 3 or higher TRAEs occurred in 30% and 46% of patients in the datopotamab deruxtecan and docetaxel arms, respectively.

在生物标志物可评估人群中，未发现新的安全性问题，无论TROP2状态如何，3级或更高治疗相关不良事件（TRAE）的发生率相似。在TROP2-QCS生物标志物阳性肿瘤患者中，达托单抗-德鲁替康组和多西紫杉醇组分别有30%和46%的患者发生3级或更高的TRAE。

The most common Grade 3 or higher TRAEs were stomatitis (7%, 3%) and ocular surface events (3%, 0%). Grade 3 or higher adjudicated drug-related interstitial lung disease events occurred in 3% and 1% of patients in the datopotamab deruxtecan and docetaxel arms, respectively..

最常见的3级或更高级别TRAE是口腔炎（7%，3%）和眼表事件（3%，0%）。达托单抗-德鲁替康组和多西紫杉醇组分别有3%和1%的患者发生3级或更高级别的药物相关性间质性肺病事件。。

Summary of TROPION-Lung01 QCS analysis results

TROPION-Lung01 QCS分析结果总结

CI, confidence interval; HR, hazard ratio; ORR, objective response rate; PFS, progression-free survival

CI，置信区间；HR，风险比；ORR，客观回应率；PFS，无进展生存期

AstraZeneca and Roche Tissue Diagnostics collaborate to co-develop and commercialise the TROP2-QCS biomarker companion diagnostic

阿斯利康和罗氏组织诊断公司合作共同开发和商业化TROP2-QCS生物标志物伴侣诊断

AstraZeneca and Roche Tissue Diagnostics are extending their existing collaboration to co-develop a novel companion diagnostic incorporating AstraZeneca’s proprietary computational pathology platform, QCS, which will be deployed within Roche's navify® Digital Pathology image management system.

阿斯利康和罗氏组织诊断公司（Roche Tissue Diagnostics）正在扩展现有合作，共同开发一种新型的伴随诊断，该诊断结合了阿斯利康专有的计算病理学平台QCS，该平台将部署在罗氏的navify®数字病理学图像管理系统中。

Jill German, Head, Roche Tissue Diagnostics, said: “Our collaboration with AstraZeneca continues to push the boundaries of traditional cancer diagnostics. By developing an innovative Al tool that goes beyond human capabilities, the solution will be able to help determine which cancer patients are most likely to benefit from targeted therapies, potentially improving patient care.”.

罗氏组织诊断公司（Roche Tissue Diagnostics）负责人吉尔·德尔曼（Jill German）表示：“我们与阿斯利康（AstraZeneca）的合作继续推动传统癌症诊断的界限。通过开发一种超越人类能力的创新Al工具，该解决方案将能够帮助确定哪些癌症患者最有可能从靶向治疗中受益，从而可能改善患者护理。”。

Under this expanded collaboration, Roche Tissue Diagnostics and AstraZeneca will co-develop and commercialise a novel companion diagnostic in Roche’s navify® Digital Pathology platform, based on the QCS computational pathology platform, to aid pathologists in interpreting an investigational VENTANA TROP2 assay..

在这一扩大的合作下，罗氏组织诊断公司和阿斯利康公司将在罗氏的navify®数字病理学平台上，基于QCS计算病理学平台，共同开发并商业化一种新型的伴随诊断，以帮助病理学家解释研究性VENTANA TROP2分析。。

As the leading provider of pathology lab solutions, Roche Tissue Diagnostics is delivering an end-to-end digital pathology workflow from tissue staining to producing high-quality digital images that can be reliably assessed using automated clinical image analysis algorithms.

作为病理学实验室解决方案的领先供应商，罗氏组织诊断公司正在提供端到端的数字病理学工作流程，从组织染色到生成高质量的数字图像，这些图像可以使用自动临床图像分析算法进行可靠评估。

Notes

注释

Advanced non-small cell lung cancer

晚期非小细胞肺癌

Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.6 NSCLC is the most common type of lung cancer, accounting for about 80% of cases.7 Approximately 75% and 25% of NSCLC tumours are of nonsquamous or squamous histology, respectively.8  While immunotherapy and targeted therapies have improved outcomes in the 1st-line metastatic setting, most patients eventually experience disease progression and receive chemotherapy.9-11 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects.9-11.

2022年，全球诊断出近250万例肺癌病例.6 NSCLC是最常见的肺癌类型，约占病例的80%.7约75%和25%的NSCLC肿瘤分别为非鳞状或鳞状组织学[8]。虽然免疫治疗和靶向治疗在一线转移治疗中取得了改善，但大多数患者最终会出现疾病进展并接受化疗[9-11]。几十年来，化疗一直是晚期NSCLC患者的最后一种治疗方法，尽管有效性和已知的副作用有限[9-11]。

TROP2 is a protein broadly expressed in the majority of NSCLC tumours.1 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.12,13

TROP2是一种在大多数NSCLC肿瘤中广泛表达的蛋白质。目前还没有TROP2指导的ADC被批准用于治疗肺癌。12,13

TROPION-Lung01

TROPION-Lung01

TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus docetaxel (75mg/m2) in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment.

TROPION-Lung01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）与多西紫杉醇（75mg/m2）在成人局部晚期或转移性NSCLC患者中的疗效和安全性，有无可行的基因组改变，需要在事先治疗后进行全身治疗。

Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor..

具有可行基因组改变的患者先前接受过铂类化疗和经批准的靶向治疗。没有已知可行基因组改变的患者先前曾同时或顺序接受铂类化疗和PD-1或PD-L1抑制剂治疗。。

The dual primary endpoints of TROPION-Lung01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, time to response, disease control rate as assessed by both BICR and investigator, and safety..

通过盲法独立中央审查（BICR）和OS评估，TROPION-Lung01的双重主要终点是PFS。主要次要终点包括研究者评估的PFS，客观缓解率，缓解持续时间，缓解时间，BICR和研究者评估的疾病控制率以及安全性。。

TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov.

TROPION-Lung01在亚洲，欧洲，北美，大洋洲和南美招募了大约600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 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 lung cancer

阿斯利康治疗肺癌

AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most..

阿斯利康正在努力通过早期疾病的检测和治疗，使肺癌患者更接近治愈，同时也推动了科学的界限，以改善耐药和晚期环境中的结果。通过定义新的治疗目标和研究创新方法，该公司旨在将药物与最能受益的患者相匹配。。

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action..

该公司的综合投资组合包括领先的肺癌药物和下一波创新，包括Tagrisso（osimertinib）和Iressa（吉非替尼）；Imfinzi（durvalumab）和Imjudo（tremelimumab）；；Orpathys（savolitinib）与HUTCHMED合作；以及跨越不同行动机制的潜在新药和组合管道。。

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

阿斯利康是肺癌雄心联盟的创始成员，该联盟是一个全球联盟，致力于加速创新，为肺癌患者提供有意义的改善，包括治疗和其他治疗。

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.

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.

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。