TOKYO & MUNICH--(BUSINESS WIRE)--ENHERTU® (trastuzumab deruxtecan) has been approved in the European Union (EU) as a monotherapy for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose tumors have an activating HER2 (ERBB2) mutation and who require systemic therapy following platinum-based chemotherapy with or without immunotherapy..

TOKYO＆MUNICH-（BUSINESS WIRE）-ENHERTU®（曲妥珠单抗deruxtecan）已被欧盟（EU）批准用作治疗晚期非小细胞肺癌（NSCLC）成人患者的单一疗法。肿瘤具有活化的HER2（ERBB2）突变，并且在有或没有免疫疗法的铂类化疗后需要全身治疗。。

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

ENHERTU是由Daiichi Sankyo（TSE:4568）和AstraZeneca（LSE/STO/纳斯达克：AZN）共同开发和商业化的特异性工程HER2定向抗体-药物偶联物（ADC）。

The approval by the European Commission (EC) follows the positive opinion of the Committee for Medicinal Products for Human Use (CHMP) and is based on results from the DESTINY-Lung02 phase 2 trial presented at the IASLC 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer and simultaneously published in the Journal of Clinical Oncology..

欧盟委员会（EC）的批准遵循人用药品委员会（CHMP）的积极意见，并基于国际肺癌研究协会主办的IASLC 2023世界肺癌会议上提交的DESTINY-Lung02第二阶段试验结果同时发表在临床肿瘤学杂志上。。

In DESTINY-Lung02, ENHERTU (5.4 mg/kg) demonstrated a confirmed objective response rate (ORR) of 49.0% (95% confidence interval [CI]: 39.0-59.1) in patients with previously treated advanced or metastatic HER2 mutant NSCLC as assessed by blinded independent central review (BICR). One (1.0%) complete response (CR) and 49 (48.0%) partial responses (PR) were observed.

在DESTINY-Lung02中，ENHERTU（5.4 mg/kg）证实先前治疗的晚期或转移性HER2突变NSCLC患者的客观缓解率（ORR）为49.0%（95%置信区间[CI]:39.0-59.1）通过盲法独立中央审查（BICR）评估。观察到一个（1.0%）完全反应（CR）和49个（48.0%）部分反应（PR）。

The median duration of response (DOR) was 16.8 months (95% CI: 6.4-not estimable [NE])..

中位反应持续时间（DOR）为16.8个月（95%CI:6.4-不可估计[NE]）。。

“HER2 mutant non-small cell lung cancer is more commonly diagnosed in patients who are younger and female, and there are limited treatment options, which often results in a poor prognosis,” said Professor Martin Reck, MD, Head of Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany. “ENHERTU is the first HER2 directed therapy to demonstrate strong and durable results for these patients, and this approval in the EU marks an important step forward in how the disease can be treated.”.

“HER2突变型非小细胞肺癌更常见于年轻和女性患者，治疗方案有限，往往导致预后不良，”德国Grosshansdorf肺诊所肿瘤科主任Martin Reck教授说。“ENHERTU是第一个为这些患者展示强大而持久的HER2定向治疗方法，欧盟的这一批准标志着疾病治疗方法迈出了重要的一步。”。

“Since our initial approval of ENHERTU for metastatic breast cancer in the EU more than two years ago, we have remained committed to bringing this innovative antibody drug conjugate to more patients with HER2 targetable tumors, especially those that have previously not been eligible for treatment with a HER2 directed therapy,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc.

“自从两年前我们在欧盟首次批准ENHERTU用于转移性乳腺癌以来，我们一直致力于将这种创新的抗体-药物偶联物应用于更多HER2靶向肿瘤患者，特别是那些以前没有资格接受治疗的患者HER2定向治疗，“全球肿瘤业务负责人Ken Keller说，第一三共公司总裁兼首席执行官。

“With today’s news, ENHERTU is the first antibody drug conjugate approved for lung cancer in the EU and is now approved in three different tumor types.”.

“有了今天的消息，ENHERTU是欧盟批准用于肺癌的第一种抗体-药物偶联物，现在已被批准用于三种不同的肿瘤类型。”。

“Understanding the molecular drivers behind a lung cancer diagnosis is critical, and while there are now targeted options for many patients, those with HER2 mutant non-small cell lung cancer have had few treatment options, none of which have been approved to treat their specific type of lung cancer,” said Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca.

“了解肺癌诊断背后的分子驱动因素至关重要，虽然现在有许多患者有针对性的选择，但HER2突变型非小细胞肺癌患者的治疗方案很少，没有一种被批准用于治疗他们特定类型的肺癌，“阿斯利康肿瘤学业务部门执行副总裁戴夫·弗雷德里克森（Dave Fredrickson）说。

“ENHERTU is the first HER2 directed option approved for HER2 mutant disease and confirms the relevance of HER2 as a target in lung cancer.”.

“ENHERTU是第一个批准用于HER2突变疾病的HER2定向选择，并证实了HER2作为肺癌靶点的相关性。”。

In DESTINY-Lung02, the safety profile of ENHERTU was consistent with other trials of ENHERTU with no new safety signals observed. Grade 3 or grade 4 treatment-related adverse events from a pooled safety analysis of patients treated with at least one dose of ENHERTU 5.4 mg/kg across multiple tumor types in clinical studies (n=1,449) included neutropenia (17.0%), anemia (9.5%), fatigue (8.4%), leukopenia (6.4%), nausea (5.9%), thrombocytopenia (5.0%), lymphopenia (4.8%), hypokalemia (3.8%), transaminases increased (3.6%), vomiting (2.7%), diarrhea (2.0%), decreased appetite (1.7%), pneumonia (1.4%) and ejection fraction decreased (1.1%).

在DESTINY-Lung02中，ENHERTU的安全性与ENHERTU的其他试验一致，没有观察到新的安全信号。在临床研究（n=1449）中用多种肿瘤类型的至少一剂ENHERTU 5.4mg/kg治疗的患者的汇总安全性分析的3级或4级治疗相关不良事件包括中性粒细胞减少症（17.0%），贫血（9.5%），疲劳（8.4%），白细胞减少（6.4%），恶心（5.9%），血小板减少症（5.0%），淋巴细胞减少症（4.8%），低钾血症（3.8%），转氨酶升高（3.6%），呕吐（2.7%），腹泻（2.0%），食欲下降（1.7%），肺炎（1.4%）和射血分数下降（1.1%）。

Grade 5 adverse reactions occurred in 1.4% of patients, including interstitial lung disease (1.0%)..

1.4%的患者发生5级不良反应，包括间质性肺病（1%）。。

Financial Considerations

财务考虑

Following approval in the EU, an amount of $75 million is due from AstraZeneca to Daiichi Sankyo as a milestone payment in HER2 mutant non-small cell lung cancer. Sales of ENHERTU in most EU territories are recognized by Daiichi Sankyo. For further details on the financial arrangements, please consult the collaboration agreement from March 2019..

经欧盟批准后，阿斯利康向第一三共提供7500万美元，作为HER2突变型非小细胞肺癌的里程碑付款。ENHERTU在大多数欧盟地区的销售得到第一三共的认可。有关财务安排的更多详细信息，请参阅2019年3月的合作协议。。

About DESTINY-Lung02

关于命运-Lung02

DESTINY-Lung02 is a global, randomized phase 2 trial evaluating the safety and efficacy of ENHERTU in patients with HER2 mutant unresectable and/or metastatic NSCLC with disease recurrence or progression during or after at least one regimen of prior anticancer therapy that must have contained a platinum-based chemotherapy.

DESTINY-Lung02是一项全球性随机2期临床试验，评估ENHERTU在HER2突变不可切除和/或转移性NSCLC患者中的安全性和有效性，这些患者在至少一种先前的抗癌治疗方案期间或之后患有疾病复发或进展铂类化疗。

Patients were randomized 2:1 to receive ENHERTU 5.4 mg/kg (n=102) or ENHERTU 6.4 mg/kg (n=50)..

患者随机2:1接受ENHERTU 5.4 mg/kg（n=102）或ENHERTU 6.4 mg/kg（n=50）。。

The primary endpoint of the trial is confirmed ORR as assessed by BICR. Secondary endpoints include disease control rate, DOR and progression-free survival assessed by investigator and BICR, overall survival and safety. DESTINY-Lung02 enrolled 152 patients at multiple sites, including Asia, Europe, Oceania and North America.

通过BICR评估，试验的主要终点是确认的ORR。次要终点包括疾病控制率，研究者和BICR评估的DOR和无进展生存期，总生存期和安全性。DESTINY-Lung02在多个地点招募了152名患者，包括亚洲，欧洲，大洋洲和北美。

For more information about the trial, visit ClinicalTrials.gov..

有关该试验的更多信息，请访问ClinicalTrials.gov。。

About HER2 Mutant NSCLC

关于HER2突变NSCLC

Lung cancer is the second most common form of cancer globally with more than two million cases diagnosed in 2020.1 In Europe, lung cancer is the third most commonly diagnosed cancer with more than 477,000 cases diagnosed in 2020.2 Lung cancer is also the leading cause of cancer-related deaths in Europe, with nearly 400,000 deaths reported in 2020.2 Prognosis is particularly poor for patients with metastatic NSCLC as only approximately 9% will live beyond five years after diagnosis.3.

肺癌是全球第二大常见癌症形式，2020年诊断出超过200万例.1在欧洲，肺癌是第三大常见癌症，2020年诊断出超过477000例.2肺癌也是癌症相关死亡的主要原因在欧洲，2020年报告有近40万人死亡.2转移性NSCLC患者的预后特别差，因为只有约9%的患者在诊断后超过5年。

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of multiple tumor types. Certain HER2 (ERBB2) gene alterations (called HER2 mutations) have been identified in patients with non-squamous NSCLC as a distinct molecular target, and occur in approximately 2% to 4% of patients with this type of lung cancer.4,5 While HER2 gene mutations can occur in a range of patients, they are more commonly found in patients with NSCLC who are younger, female and have never smoked.6 HER2 gene mutations have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases.7 Next-generation sequencing has been utilized in the identification of HER2 (ERBB2) mutations.8,9.

HER2是在多种肿瘤类型的表面上表达的酪氨酸激酶受体生长促进蛋白。某些HER2（ERBB2）基因改变（称为HER2突变）已在非鳞状NSCLC患者中被确定为一种独特的分子靶点，并且在约2%至4%的此类肺癌患者中发生.4,5虽然HER2基因突变可发生在一系列患者中，但它们更常见于年龄较小的NSCLC患者，HER2基因突变与癌细胞生长和预后不良独立相关，脑转移发生率增加[7]。下一代测序已被用于鉴定HER2（ERBB2）突变[8,9]。

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（仅在美国的曲妥珠单抗deruxtecan；fam曲妥珠单抗deruxtecan nxki）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项目。

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抑制剂有效负载（exatecan衍生物，DXd）的HER2单克隆抗体组成。。

ENHERTU (5.4 mg/kg) is approved in more than 55 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a (or one or more) 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55个以上的国家获得批准，用于治疗无法切除或转移的HER2阳性乳腺癌成年患者，这些患者先前接受过（或一种或多种）基于抗HER2的方案，无论是在转移环境中还是在新辅助或辅助环境中，根据DESTINY-Breast03试验的结果，在完成治疗期间或之后的六个月内发生疾病复发。。

ENHERTU (5.4 mg/kg) is approved in more than 40 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/in-situ hybridization (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40多个国家获得批准，用于治疗无法切除或转移的HER2低（IHC 1+或IHC 2+/原位杂交（ISH）-）乳腺癌成年患者先前在转移环境中进行全身治疗或在完成辅助化疗期间或之后的六个月内发生疾病复发DESTINY-Breast04审判。。

ENHERTU (5.4 mg/kg) is approved in more than 30 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30多个国家获得批准，用于治疗无法切除或转移的NSCLC成人患者，这些患者的肿瘤具有激活的HER2（ERBB2）突变，通过当地或地区批准的检测，并且已接受根据DESTINY-Lung02试验结果进行的先前全身治疗。

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的临床益处的验证和描述。。

ENHERTU (6.4 mg/kg) is approved in more than 30 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 and/or DESTINY-Gastric02 trials..

ENHERTU（6.4 mg/kg）已在全球30多个国家获得批准，用于治疗局部晚期或转移性HER2阳性胃或胃食管连接（GEJ）腺癌的成人患者，这些患者之前接受过基于曲妥珠单抗的治疗方案。来自DESTINY-Gastric01和/或DESTINY-Gastric02试验。。

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。与其他抗癌治疗（如免疫疗法）相结合的试验也在进行中。

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 (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月合作开展全球合作，共同开发和商业化ENHERTU，2020年7月datopotamab deruxtecan（Dato DXd），日本除外，第一三共为每个ADC保留专有权。第一三共负责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. 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.

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。目前正在联合开发HER3定向ADC Patritumab deruxtecan（HER3-DXd），CDH6定向ADC ifinatamab deruxtecan（I-DXd）和raludotatug deruxtecan（R-DXd）Merck＆Co.，Inc.，Rahway，N.J。

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

美国。第一三共公司正在开发TA-MUC1定向ADC DS-3939。。

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。。

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工具书类

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