TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--Topline results from the TROPION-Breast01 phase 3 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..

东京和新泽西州巴斯金岭（BUSINESS WIRE）--与研究者选择的化疗相比，达托巴单抗-德鲁替康（Dato DXd）的TROPION-BRAST01 3期试验的Topline结果先前符合无进展生存期（PFS）的双重主要终点，在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-）乳腺癌患者的最终总生存期（OS）分析中未达到统计学显着性。。

Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Datopotamab deruxtecan是由Daiichi Sankyo（TSE:4568）发现并由Daiichi Sankyo和AstraZeneca（LSE/STO/Nasdaq:AZN）联合开发的特异性工程TROP2定向DXd抗体-药物偶联物（ADC）。

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 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ADC，包括ENHERTU®（曲妥珠单抗-德鲁替康），患者疾病进展或停止治疗后的后续治疗可能会影响生存结果。

“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,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “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.”.

Daiochi Sankyo全球研发主管Ken Takeshita医学博士说：“达托巴单抗deruxtecan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次要指标的支持。”。“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巴单抗德鲁替康成为可以受益的患者的另一种潜在选择。”。

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

阿斯利康肿瘤学研发执行副总裁、MBBChir博士苏珊·加尔布雷斯（SusanGalbraith）说：“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，使患者受益。”。“根据TROPION-Breast01的结果，有证据表明达托帕单抗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 program 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。”。

The data will be presented at an upcoming 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, Daiichi Sankyo and AstraZeneca 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 3 trials..

除TROPION-Breast01外，Daiichi Sankyo和AstraZeneca正在TROPION-Breast02，TROPION-Breast03，TROPION-Breast04和TROPION-Breast05 3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。。

About TROPION-Breast01

关于TROPION-Breast01

TROPION-Breast01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/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3期临床试验，评估达托单抗-德鲁替康（6.0 mg/kg）与研究者选择单药化疗（埃里布林，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，他们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。

About Hormone Receptor Positive Breast Cancer

关于激素受体阳性乳腺癌

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常见癌症，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，预计不到35%的患者在诊断后能活五年。

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.4 However, following two lines of endocrine therapy, further efficacy with additional endocrine treatment is often limited.4 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.4,5,6,7.

大约70%的确诊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连续给予[4]。然而，在两种内分泌治疗后，额外内分泌治疗的进一步疗效往往是有限的[4]。内分泌治疗后目前的护理标准是化疗，这与不良反应率和结果有关[4,5,6,7]。

TROP2 is a protein broadly expressed in HR positive, HER2 negative breast cancer and is associated with increased tumor 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

About Datopotamab Deruxtecan (Dato-DXd)

关于达托帕马·德鲁克斯坦（Dato DXd）

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 programs 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 humanized 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 program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including non-small cell lung cancer, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 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，超过20项试验评估了达托单抗deruxtecan在多种癌症中的疗效和安全性，包括非小细胞肺癌，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3期临床试验和5项乳腺癌3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。。

About the Daiichi Sankyo and AstraZeneca Collaboration

关于第一三共公司与阿斯利康公司的合作

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan (Dato-DXd) 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..

第一三共和阿斯利康于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，datopotamab deruxtecan（Dato DXd）在日本除外，在日本，第一三共对每个ADC拥有专有权。Daiichi Sankyo负责ENHERTU和datopotamab deruxtecan的制造和供应。。

About the ADC Portfolio of Daiichi Sankyo

关于第一三共的ADC投资组合

The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.

Daiichi Sankyo ADC组合由七个临床开发中的ADC组成，这些ADC由Daiichi Sankyo内部发现的两个不同的ADC技术平台精心打造而成。

The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca.

临床开发中最深入的ADC平台是Daiichi Sankyo的DXd ADC技术，其中每个ADC由单克隆抗体组成，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）。。

Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo..

Patritumab deruxtecan（HER3 DXd），一种HER3导向的ADC，ifinatamab deruxtecan（I-DXd），一种B7-H3导向的ADC，以及raludotatug deruxtecan（R-DXd），一种CDH6导向的ADC，正在与默克公司联合开发和全球商业化。DS-3939是一种TA-MUC1定向的ADC，由Daiichi Sankyo开发。。

The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.

第二个Daiichi Sankyo ADC平台由连接到修饰的吡咯并苯并二氮杂卓（PBD）有效载荷的单克隆抗体组成。DS-9606是一种CLDN6定向的PBD ADC，是利用该平台进行临床开发的几个计划ADC中的第一个。

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

Datopotamab deruxtecan，ifinatamab deruxtecan，patritumab deruxtecan，raludotatug deruxtecan，DS-3939和DS-9606是尚未在任何国家批准用于任何适应症的研究药物。安全性和有效性尚未确定。

About Daiichi Sankyo

关于第一三共

Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need.

拥有120多年的经验，第一三共利用其世界一流的科学和技术，为癌症，心血管疾病和其他医疗需求未得到满足的疾病患者创造新的模式和创新药物。