TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been granted Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of unresectable or metastatic hormone receptor positive HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC >0 <1+) breast cancer patients who have received either two lines of endocrine therapy in the metastatic setting, or one line of endocrine therapy if they had demonstrated disease progression within six months of starting first-line treatment with endocrine therapy in combination with a CDK4/6 inhibitor or within 24 months of the start of adjuvant endocrine therapy..

东京和新泽西州巴斯金岭（BUSINESS WIRE）--ENHERTU®（fam曲妥珠单抗-德鲁昔单抗nxki）已在美国获得突破性治疗指定（BTD），用于治疗不可切除或转移性激素受体阳性的HER2低（IHC 1+或IHC 2+/ISH-）或HER2超低（IHC>0<1+）乳腺癌患者，如果他们在开始内分泌治疗联合CDK4/6抑制剂的一线治疗的六个月内或在接受内分泌治疗的24个月内证明疾病进展开始辅助内分泌治疗。

ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

ENHERTU是由Daiichi Sankyo（TSE:4568）发现的一种专门设计的HER2定向DXd抗体-药物偶联物（ADC），由Daiichi Sankyo和AstraZeneca（LSE/STO/Nasdaq:AZN）联合开发和商业化。

The U.S. Food and Drug Administration (FDA) BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines..

美国食品和药物管理局（FDA）BTD旨在加速潜在新药的开发和监管审查，这些新药旨在治疗严重疾病并解决严重未满足的医疗需求。该药物需要显示出令人鼓舞的初步临床结果，证明与现有药物相比，临床显着终点有实质性改善。。

The FDA granted this BTD based on data from the DESTINY-Breast06 phase 3 trial presented as a late-breaking oral session at the 2024 American Society of Clinical Oncology (#ASCO24) Annual Meeting.

FDA根据DESTINY-Breast06第3阶段试验的数据批准了这项BTD，该试验是在2024年美国临床肿瘤学会（ASCO24）年会上作为最新的口头会议提交的。

“If approved, ENHERTU could once again change the treatment paradigm for certain patients with breast cancer, pushing past old boundaries and broadening the number of people who may be eligible for a HER2 directed therapy,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “The designation also showcases Daiichi Sankyo’s commitment to pioneering cutting-edge science to deliver medicines like ENHERTU that create new standards of care for patients with cancer.”.

“如果获得批准，ENHERTU可以再次改变某些乳腺癌患者的治疗模式，打破旧的界限，扩大可能有资格接受HER2指导治疗的人数，”第一三共研发全球负责人Ken Takeshita医学博士说。“该名称还表明，第一三共致力于开创尖端科学，提供像ENHERTU这样的药物，为癌症患者创造新的护理标准。”。

ENHERTU has received eight BTDs, including four in metastatic breast cancer. In addition to the new BTD, the three previous BTDs for breast cancer were for later-line HER2 low metastatic breast cancer, second-line HER2 positive metastatic breast cancer and later-line HER2 positive metastatic breast cancer.

恩赫图已经接受了八种BTD，其中包括四种转移性乳腺癌。除新的BTD外，之前用于乳腺癌的三种BTD分别用于晚期HER2低转移性乳腺癌，二线HER2阳性转移性乳腺癌和晚期HER2阳性转移性乳腺癌。

ENHERTU also received four additional BTDs, including for HER2 positive (IHC 3+) metastatic solid tumors, HER2 positive metastatic colorectal cancer, HER2 (ERBB2) mutant metastatic non-small cell lung cancer (NSCLC) and HER2 positive metastatic gastric cancer. The new BTD for ENHERTU also represents the eleventh BTD across Daiichi Sankyo’s oncology pipeline..

ENHERTU还接受了另外四种BTD，包括HER2阳性（IHC 3+）转移性实体瘤，HER2阳性转移性结直肠癌，HER2（ERBB2）突变转移性非小细胞肺癌（NSCLC）和HER2阳性转移性胃癌。ENHERTU的新BTD也代表了第一三共肿瘤管道中的第十一个BTD。。

About DESTINY-Breast06

关于DESTINY-Breast06

DESTINY-Breast06 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab paclitaxel) in patients with HR positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (defined as IHC 0 with membrane staining [IHC >0 <1+]) advanced or metastatic breast cancer.

DESTINY-Breast06是一项全球性，随机，开放标签的3期临床试验，评估了ENHERTU（5.4 mg/kg）与研究者选择的化疗（卡培他滨，紫杉醇或nab-紫杉醇）对HR阳性，HER2低（IHC 1+或IHC 2+/ISH-）或HER2超低（定义为具有膜染色的IHC 0[IHC>0<1+]）晚期或转移性乳腺癌患者的疗效和安全性。

Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients also were eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting first-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months..

试验中的患者之前没有接受过晚期或转移性疾病的化疗，并且在转移性环境中接受了至少两行先前的内分泌治疗。如果患者在转移性环境中接受过一种先前的内分泌治疗联合CDK4/6抑制剂，并且在开始一线治疗的六个月内经历了疾病进展，或者接受了内分泌治疗作为辅助治疗，并且在24个月内经历了疾病复发，则患者也符合条件。。

The primary endpoint of DESTINY-Breast06 is progression-free survival (PFS) in the HR positive, HER2 low patient population as measured by blinded independent central review (BICR). Key secondary endpoints include PFS by BICR in the overall trial population (HER2 low and HER2 ultralow), overall survival (OS) in patients in the HER2 low patient population and OS in the overall trial population.

DESTINY-Breast06的主要终点是通过盲法独立中央评估（BICR）测量的HR阳性，HER2低患者人群的无进展生存期（PFS）。关键的次要终点包括BICR在总体试验人群（HER2低和HER2超低）中的PFS，HER2低患者人群中患者的总生存期（OS）和总体试验人群中的OS。

Other secondary endpoints include objective response rate, duration of response, time to first subsequent treatment or death, time to second subsequent treatment or death and safety. Analysis of the HER2 ultralow subgroup was not powered to demonstrate statistical significance..

其他次要终点包括客观缓解率，缓解持续时间，首次后续治疗或死亡时间，第二次后续治疗或死亡时间和安全性。HER2超低亚组的分析无法证明统计学意义。。

DESTINY-Breast06 enrolled 866 patients (n=713 for HER2 low and n=153 for HER2 ultralow) at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

DESTINY-Breast06在亚洲，欧洲，北美，大洋洲和南美洲的多个地点招募了866名患者（HER2-low n=713，HER2-ultralow n=153）。有关该试验的更多信息，请访问ClinicalTrials.gov。

About Breast Cancer and HER2 Expression

关于乳腺癌和HER2表达

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.1 In the U.S., more than 300,000 cases of breast cancer are diagnosed annually.2 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.3.

乳腺癌是全球第二大常见癌症，也是导致癌症相关死亡的主要原因之一。1 2022年诊断出200多万例乳腺癌病例，全球死亡人数超过665000人。1在美国，每年诊断出30多万例乳腺癌。2虽然早期乳腺癌患者的生存率很高，但只有约30%的被诊断患有或进展为转移性疾病的患者预计在诊断后能活五年。

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including breast cancer.4 Patients with high levels of HER2 expression (IHC 3+ or IHC2+/ISH+) are classified as HER2 positive and treated with HER2 targeted therapies, representing approximately 15 to 20% percent of all breast cancers.5 Historically, tumors that were not classified as HER2 positive were classified as HER2 negative, despite the fact that many of these tumors still carry some level of HER2 expression.6 It is estimated that approximately 60% to 65% of HR positive, HER2 negative breast cancers are HER2 low and potentially an additional 25% may be HER2 ultralow.7,8.

HER2是一种酪氨酸激酶受体生长促进蛋白，在包括乳腺癌在内的许多类型的肿瘤表面表达[4]。HER2表达水平高（IHC 3+或IHC2+/ISH+）的患者被归类为HER2阳性，并接受HER2靶向治疗，约占所有乳腺癌的15%至20%[5]。历史上，未被归类为HER2阳性的肿瘤被归类为HER2阴性，尽管事实上许多这些肿瘤仍然携带一定水平的HER2表达[6]。据估计，大约60%至65%的HR阳性，HER2阴性乳腺癌是HER2低，可能还有25%是HER2超低[7,8]。（笑声）。

Endocrine therapies are widely given consecutively in the early lines of treatment for HR positive metastatic breast cancer. However, following two lines of endocrine therapy, further efficacy with additional endocrine treatment is often limited. 9 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.9,10,11,12.

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。然而，在两种内分泌治疗之后，额外内分泌治疗的进一步疗效通常是有限的。目前内分泌治疗后的护理标准是化疗，这与不良反应率和结果有关[9,10,11,12]。

Prior to the approval of ENHERTU following chemotherapy in HER2 low metastatic breast cancer based on the DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2 low expression.13 There are no targeted therapies specifically approved for patients with HER2 ultralow expression.14.

在基于DESTINY-Breast04试验的HER2低转移性乳腺癌化疗后批准ENHERTU之前，没有专门针对HER2低表达患者的靶向治疗.13没有专门针对HER2超低表达患者的靶向治疗.14。

About ENHERTU

关于ENHERTU

ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform.

ENHERTU（曲妥珠单抗deruxtecan；fam曲妥珠单抗deruxtecan nxki仅在美国）是HER2定向的ADC。ENHERTU采用第一三共专有的DXd ADC技术设计，是第一三共肿瘤学组合中的领先ADC，也是阿斯利康ADC科学平台中最先进的程序。

ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers..

ENHERTU由HER2单克隆抗体组成，该抗体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）。

ENHERTU (5.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial..

ENHERTU（5.4 mg/kg）已在全球65多个国家获得批准，用于治疗不可切除或转移性HER2阳性（IHC 3+或原位杂交（ISH）+）乳腺癌的成年患者，这些患者先前曾接受过基于抗HER2的方案，无论是在转移性环境中还是在新辅助或辅助性环境中，并且根据DESTINY-Breast03试验的结果，在完成治疗后的六个月内或六个月内出现疾病复发。。

ENHERTU (5.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial..

ENHERTU（5.4 mg/kg）已在全球65多个国家获得批准，用于治疗无法切除或转移性HER2-low（IHC 1+或IHC 2+/ISH-）乳腺癌的成年患者，这些患者先前曾在转移性环境中接受过全身治疗，或根据DESTINY-Breast04试验的结果在完成辅助化疗后的六个月内或六个月内出现疾病复发。。

ENHERTU (5.4 mg/kg) is approved in more than 35 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial.

ENHERTU（5.4 mg/kg）已在全球35多个国家获得批准，用于治疗无法切除或转移性NSCLC的成年患者，这些患者的肿瘤具有激活的HER2（ERBB2）突变，这是通过当地或地区批准的测试检测到的，并且已经根据DESTINY-Lung02试验的结果接受了先前的全身治疗。

Continued approval in the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial..

美国对该适应症的持续批准可能取决于验证性试验中临床益处的验证和描述。。

ENHERTU (6.4 mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials.

ENHERTU（6.4 mg/kg）在全球45多个国家被批准用于治疗局部晚期或转移性HER2阳性（IHC 3+或IHC 2+/ISH+）胃或胃食管交界处（GEJ）腺癌的成年患者，这些患者根据DESTINY-Gastric01，DESTINY-Gastric02和/或DESTINY-Gastric06试验的结果接受了先前基于曲妥珠单抗的方案。

Full approval in China for this indication will depend on whether a randomized controlled confirmatory clinical trial can demonstrate clinical benefit in this population..

中国对该适应症的完全批准将取决于随机对照验证性临床试验是否可以证明该人群的临床益处。

ENHERTU (5.4 mg/kg) is approved in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.

ENHERTU（5.4 mg/kg）在美国被批准用于治疗无法切除或转移性HER2阳性（IHC 3+）实体瘤的成年患者，这些患者先前接受过全身治疗，并且根据DESTINY-PanTumor02，DESTINY-Lung01和DESTINY-CRC02试验的疗效结果没有令人满意的替代治疗选择。

Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial..

在美国继续批准该适应症可能取决于验证性试验中临床益处的验证和描述。

About the ENHERTU Clinical Development Program

关于ENHERTU临床开发计划

A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.

一项全面的全球临床开发计划正在评估ENHERTU单药治疗多种HER2靶向癌症的疗效和安全性。与免疫疗法等其他抗癌治疗相结合的试验也正在进行中。

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..

第一三共与阿斯利康于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，但在日本，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 DXd ADC Portfolio of Daiichi Sankyo

关于第一三共的DXd ADC投资组合

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. 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 & Co., Inc., Rahway, N.J.

Daiichi Sankyo的DXd ADC组合目前由六个ADC组成，这些ADC在多种癌症的临床开发中。针对HER2的ADC ENHERTU和针对TROP2的ADC datopotamab deruxtecan（Dato DXd）正在与阿斯利康联合开发并在全球商业化。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Merck＆Co.，Inc.，Rahway，N.J.联合开发并在全球商业化。

USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo..

美国。DS-3939是一种TA-MUC1定向的ADC，由Daiichi Sankyo开发。。

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，以靶向并传递表达特定细胞表面抗原的癌细胞内的细胞毒性有效载荷，每个ADC由单克隆抗体组成，该单克隆抗体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）。

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.

Daiichi Sankyo是一家创新的全球医疗保健公司，致力于社会的可持续发展，发现、开发和提供新的护理标准，以丰富世界各地的生活质量。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。