TOKYO & MUNICH & BASKING RIDGE, N.J.--(BUSINESS WIRE)--Positive topline results from the TROPION-Breast01 phase 3 trial showed datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant and clinically meaningful improvement for the primary endpoint of progression-free survival (PFS) compared to investigator’s choice of chemotherapy 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，慕尼黑和巴斯金岭，N.J.-（BUSINESS WIRE）-来自TROPION-Breast01第3阶段试验的阳性topline结果显示，与研究者对无法手术或转移性激素受体（HR）阳性患者的化疗选择相比，datopotamab deruxtecan（Dato-DXd）在无进展生存期（PFS）的主要终点方面显示出统计学上显着且临床上有意义的改善，HER2低或阴性（IHC 0，IHC 1+或IHC 2+/ISH-）乳腺癌先前曾接受基于内分泌的治疗和至少一种全身治疗。。

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

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

Data for the dual primary endpoint of overall survival (OS) were not mature at this interim analysis and the trial will continue as planned to assess OS.

总体生存（OS）双重主要终点的数据在此中期分析中尚未成熟，试验将按计划继续评估OS。

The safety profile of datopotamab deruxtecan was consistent with previous clinical trials in breast cancer with no new safety signals identified. All grade interstitial lung disease rates were low.

datopotamab deruxtecan的安全性与之前的乳腺癌临床试验一致，未发现新的安全性信号。所有级别的间质性肺病发病率都很低。

More than two million people worldwide are diagnosed with breast cancer each year.1 HR positive, HER2 low or negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.1,2 Standard initial treatment for these patients is endocrine therapy but most patients with advanced disease will develop resistance, underscoring the need for additional options.3,4 TROP2 is a protein broadly expressed in HR positive, HER2 low or negative breast cancer.5,6.

全世界每年有超过200万人被诊断患有乳腺癌.1 HR阳性，HER2低或阴性乳腺癌是最常见的亚型，占诊断病例的65%以上.1,2标准初始治疗这些患者是内分泌治疗，但大多数晚期疾病患者会产生抵抗力，强调需要额外的选择.3,4 TROP2是一种在HR阳性，HER2低或阴性乳腺癌中广泛表达的蛋白质.5,6。

“The positive topline results from TROPION-Breast01 demonstrate the potential for datopotamab deruxtecan to become an important treatment option for patients with HR positive, HER2 low or negative breast cancer in the second-line metastatic setting,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo.

“TROPION-Breast01的阳性结果表明，datopotamab deruxtecan有可能成为二线转移环境中HR阳性，HER2低或阴性乳腺癌患者的重要治疗选择，”Ken Takeshita博士说，第一三共全球研发主管。

“We look forward to realizing the full potential of this TROP2 directed antibody drug conjugate across breast cancer subtypes through our ongoing phase 3 program, including two trials in patients with triple negative breast cancer.”.

“我们期待通过我们正在进行的第3阶段计划，包括对三阴性乳腺癌患者的两项试验，实现这种TROP2定向抗体-药物偶联物在乳腺癌亚型中的全部潜力。”。

“Today’s TROPION-Breast01 news is a significant development for patients with HR positive, HER2 low or negative metastatic breast cancer whose tumors have become insensitive to endocrine therapy and who currently face poor outcomes,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca.

“今天的TROPION-Breast01新闻对于HR阳性，HER2低或阴性转移性乳腺癌患者来说是一项重大发展，这些患者的肿瘤对内分泌治疗不敏感，目前面临不良后果，”执行副总裁Susan Galbraith博士，博士阿斯利康肿瘤研发部总裁。

“We are encouraged by these positive results.”.

“我们对这些积极成果感到鼓舞。”。

Detailed results from the TROPION-Breast01 trial will be presented at an upcoming medical meeting and shared with regulatory authorities.

TROPION-Breast01试验的详细结果将在即将召开的医学会议上公布，并与监管机构分享。

Daiichi Sankyo and AstraZeneca have two additional phase 3 trials evaluating datopotamab deruxtecan in breast cancer. TROPION-Breast02 is comparing datopotamab deruxtecan to chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for anti-PDL1 therapy.

Daiichi-Sankyo和AstraZeneca还有另外两项评估datopotamab deruxtecan治疗乳腺癌的3期临床试验。TROPION-Breast02正在比较datopotamab deruxtecan与先前未治疗的局部复发性不可手术或转移性三阴性乳腺癌（TNBC）患者的化疗，这些患者不是抗PDL1治疗的候选者。

TROPION-Breast03 is evaluating datopotamab deruxtecan with and without durvalumab versus investigator’s choice of therapy in patients with stage I-III TNBC with residual disease after neoadjuvant therapy..

TROPION-Breast03正在评估datopotamab deruxtecan联合或不联合durvalumab与研究者选择治疗I-III期TNBC患者新辅助治疗后残留疾病的疗效。。

About TROPION-Breast01

关于TROPION-Breast01

TROPION-Breast01 is global, randomized, multicenter, open-label phase 3 trial evaluating the safety and efficacy of datopotamab deruxtecan versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in patients with inoperable or metastatic HR positive, HER2 low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on or are not suitable for endocrine therapy per investigator assessment and at least one systemic therapy..

TROPION-Breast01是一项全球性，随机，多中心，开放标签的3期临床试验，评估了datopotamab deruxtecan与研究者选择单药化疗（艾日布林，卡培他滨，长春瑞滨或吉西他滨）对无法手术或转移性HR阳性患者的安全性和有效性，HER2低或阴性（IHC 0，IHC 1+或IHC 2+/ISH-）乳腺癌，根据研究者评估和至少一种全身治疗进展或不适合内分泌治疗。。

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

TROPION-Breast01的双重主要终点是通过盲法独立中央评估（BICR）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，疾病控制率和首次后续治疗的时间。

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

TROPION-Breast01在亚洲，欧洲，北美，南美和非洲的地点招收了700多名患者。欲了解更多信息，请访问ClinicalTrials.gov。

About HR Positive, HER2 Low or Negative Breast Cancer

关于HR阳性，HER2低或阴性的乳腺癌

Breast cancer is the most common cancer in the world and a leading cause of cancer-related death.1 More than two million breast cancer cases were diagnosed in 2020 with nearly 685,000 deaths globally.1

乳腺癌是世界上最常见的癌症，也是导致癌症相关死亡的主要原因.1 2020年诊断出200多万例乳腺癌病例，全球死亡人数近685000人.1

Breast cancer is considered HR positive, HER2 low or negative when tumors test positive for estrogen and/or progesterone hormone receptors and negative for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).2,7 HR positive, HER2 low or negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.2 Approximately 30% of patients diagnosed with HR positive, HER2 low or negative metastatic breast cancer are expected to live five years after their diagnosis.2.

当肿瘤检测雌激素和/或孕激素受体阳性且HER2阴性（以IHC 0，IHC 1+或IHC 2+/ISH-的HER2评分测量）时，乳腺癌被认为是HR阳性，HER2低或阴性.2,7 HR阳性，HER2低或阴性乳腺癌是最常见的亚型，占确诊病例的65%以上.2大约30%被诊断为HR阳性，HER2低或阴性转移性乳腺癌的患者预计在诊断后存活5年。

TROP2 is a protein broadly expressed in several solid tumors, including HR positive, HER2 low or negative breast cancer.5 TROP2 expression is associated with increased tumor progression and poor survival in patients with breast cancer.5,6

TROP2是一种在几种实体瘤中广泛表达的蛋白质，包括HR阳性，HER2低或阴性乳腺癌.5 TROP2表达与乳腺癌患者肿瘤进展增加和生存率低有关.5,6

About the Daiichi Sankyo and AstraZeneca Collaboration

关于第一三共和阿斯利康的合作

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize 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..

Daiichi-Sankyo和AstraZeneca于2019年3月与ENHERTU和2020年7月的datopotamab deruxtecan进行了全球合作，共同开发和商业化，但日本Daiichi-Sankyo拥有每个ADC的专有权。第一三共负责ENHERTU和datopotamab deruxtecan的制造和供应。。

About Datopotamab Deruxtecan (Dato-DXd)

关于Datopotamab Deruxtecan（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 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定向ADC。datopotamab deruxtecan采用第一三共专有的DXd ADC技术设计，是第一三共肿瘤学管道中的六个ADC之一，也是阿斯利康ADC科学平台上最先进的项目之一。

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 development program called TROPION is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple tumors, including non-small cell lung cancer, TNBC and HR positive, HER2 low or negative breast cancer. Beyond the TROPION program, datopotamab deruxtecan also is being evaluated in novel combinations in several ongoing trials..

一项名为TROPION的综合开发计划正在全球范围内进行，超过12项试验评估了datopotamab deruxtecan在多种肿瘤中的疗效和安全性，包括非小细胞肺癌，TNBC和HR阳性，HER2低或阴性乳腺癌。除了TROPION计划之外，datopotamab deruxtecan还在几个正在进行的试验中以新颖的组合进行评估。。

About the DXd ADC Portfolio of Daiichi Sankyo

关于第一三共的DXd ADC产品组合

The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Four additional Daiichi Sankyo DXd ADCs include patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd; DS-7300), a B7-H3 directed ADC, raludotatug deruxtecan (R-DXd; DS-6000), a CDH6 directed ADC, and DS-3939, a TA-MUC1 directed ADC..

第一三共的DXd ADC产品组合目前由六种ADC组成，用于多种类型癌症的临床开发。HER2定向ADC ENHERTU和TROP2定向ADC datopotamab deruxtecan（Dato-DXd）正在与AstraZeneca共同开发和商业化。另外四个Daiichi Sankyo DXd ADC包括patritumab deruxtecan（HER3 DXd），HER3定向ADC，ifinatamab deruxtecan（I-DXd；DS-7300），B7-H3定向ADC，raludotatug deruxtecan（R-DXd；DS-6000）），CDH6定向ADC和DS-3939，TA-MUC1定向ADC。。

Designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, 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..

使用Daiichi Sankyo专有的DXd ADC技术设计，在表达特定细胞表面抗原的癌细胞内靶向并递送细胞毒性有效载荷，每个ADC由与许多拓扑异构酶I抑制剂有效载荷（exatecan衍生物，DXd）连接的单克隆抗体组成。基于四肽的可切割接头。。

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 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和DS-3939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.

第一三共是一家创新的全球医疗保健公司，为社会的可持续发展做出贡献，发现，发展和提供新的护理标准，以丰富世界各地的生活质量。凭借120多年的经验，第一三共利用其世界一流的科学技术为癌症，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。

For more information, please visit www.daiichisankyo.com..

欲了解更多信息，请访问www.daiichisankyo.com。。

References

工具书类

1 Sung H, et al. CA Cancer J Clin. 2021;10.3322/caac.21660.

Sung H等人，CA癌症J临床。2021年；10.3322/CAAC.21660。

2 National Cancer Institute. SEER cancer stat facts: female breast cancer subtypes. Accessed September 2023.

2国家癌症研究所。SEER癌症统计事实：女性乳腺癌亚型。访问时间：2023年9月。

3 Lin M, et al. J Cancer. 2020; 10.7150/jca.48944.

Lin M等人，J.癌症。2020年；10.7150/JCA.48944。

4 Lloyd M R, et al. Clin Cancer Res. 2022; 28(5):821-30.

4 Lloyd M R等人，《临床癌症研究》，2022年；28（5）：821-30。

5 Goldenberg D, et al. Oncotarget. 2018;9(48): 28989-29006.

5 Goldenberg D等人Oncotarget。2018;9(48): 28989-29006.

6 Vidula N, et al. Breast Cancer Res Treat. 2022 Aug;194(3):569-575.

6 Vidula N等人，癌症研究治疗。2022年8月；194（3）：569-575。

7 Iqbal et al. Mol Biol Int. 2014;852748.

7 Iqbal等人Mol Biol Int.2014；852748