第一三共与阿斯利康宣布ENHERTU®在美国获得转移性HER2阳性实体瘤患者的优先审评-动脉网

ENHERTU ® Granted Priority Review in the U.S. for Patients with Metastatic HER2 Positive Solid Tumors

businesswire 等信源发布 2024-01-29 14:00

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TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--Daiichi Sankyo (TSE: 4568) and AstraZeneca's (LSE/STO/Nasdaq: AZN) supplemental Biologics License Application (sBLA) for ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been accepted and granted Priority Review in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+) solid tumors who have received prior treatment or who have no satisfactory alternative treatment options..

东京和太阳岭，新泽西州--（商业新闻短讯）--第一三共（TSE:4568）和阿斯利康（LSE/STO/Nasdaq:AZN）ENHERTU®（fam曲妥珠单抗-德鲁昔单抗-nxki）的补充生物制剂许可证申请（sBLA）已在美国被接受并获得优先审查，用于治疗先前接受过的不可切除或转移性HER2阳性（免疫组织化学[IHC]3+）实体瘤的成年患者治疗或没有令人满意的替代治疗选择。。

ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

ENHERTU是一种专门设计的HER2定向抗体-药物偶联物（ADC），由第一三共和阿斯利康联合开发和商业化。

The U.S. Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available treatment options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for their regulatory decision, is May 30, 2024.

美国食品和药物管理局（FDA）优先审查药物申请，如果获得批准，将通过证明安全性或疗效改善，预防严重疾病或提高患者依从性，从而显着改善现有治疗方案。《处方药用户费用法案》（PDUFA）的日期是2024年5月30日，FDA对其监管决定的行动日期。

The Priority Review follows receipt of Breakthrough Therapy Designation granted by the FDA in August 2023 for ENHERTU in metastatic HER2 positive solid tumors..

优先审查是在2023年8月收到FDA授予的转移性HER2阳性实体瘤ENHERTU突破性治疗指定之后进行的。。

The sBLA is being reviewed under the Real-Time Oncology Review (RTOR) program and Project Orbis, two initiatives of the FDA which are designed to bring safe and effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application.

sBLA正在实时肿瘤学审查（RTOR）计划和Orbis项目下进行审查，这是FDA的两项举措，旨在尽早为患者带来安全有效的癌症治疗。RTOR允许FDA在提交完整申请之前审查申请的组成部分。

Project Orbis provides a framework for concurrent submission and review of oncology medicines among participating international partners..

Orbis项目为参与的国际合作伙伴同时提交和审查肿瘤药物提供了一个框架。。

The sBLA is based on data from the ongoing DESTINY-PanTumor02 phase 2 trial where ENHERTU demonstrated clinically meaningful and durable responses leading to a clinically meaningful survival benefit in previously treated patients across HER2 expressing advanced solid tumors. Data from other supporting trials in patients with HER2 positive IHC 3+ tumors in the ENHERTU clinical development program, including DESTINY-Lung01 and DESTINY-CRC02, also were included in the submission..

sBLA基于正在进行的DESTINY-PanTumor02 2期临床试验的数据，其中ENHERTU表现出临床上有意义且持久的反应，从而在先前接受过HER2治疗的晚期实体瘤患者中产生了临床上有意义的生存益处。来自ENHERTU临床开发计划中HER2阳性IHC 3+肿瘤患者的其他支持试验的数据，包括DESTINY-Lung01和DESTINY-CRC02，也包括在提交中。。

“The clinical benefit seen across HER2 expressing metastatic solid tumors in the DESTINY-PanTumor02 trial and ongoing data from the ENHERTU clinical development program continues to demonstrate the potential of this medicine beyond its approved indications,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo.

“在DESTINY-PanTumor02试验中，HER2表达转移性实体瘤的临床益处以及ENHERTU临床开发计划的持续数据继续证明了这种药物超出其批准适应症的潜力，”第一三共研发全球负责人Ken Takeshita医学博士说。

“If approved, ENHERTU could become the first HER2 directed therapy and antibody drug conjugate with a tumor agnostic indication, providing patients with a potential new treatment option.”.

“如果获得批准，ENHERTU可能成为第一个具有肿瘤不可知适应症的HER2定向治疗和抗体-药物偶联物，为患者提供潜在的新治疗选择。”。

“Today’s Priority Review for the first tumor agnostic submission for ENHERTU reflects the potential of this medicine to redefine the treatment of HER2 expressing cancers,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “Biomarkers for HER2 expression are already established in breast and gastric cancers, but we must now define them across tumor types.

阿斯利康（AstraZeneca）肿瘤研发执行副总裁、MBBChir博士苏珊·加尔布雷斯（SusanGalbraith）表示：“今天对ENHERTU首次提交的肿瘤不可知论的优先审查反映了这种药物重新定义表达HER2的癌症治疗的潜力。”。“HER2表达的生物标志物已经在乳腺癌和胃癌中建立，但我们现在必须在肿瘤类型中定义它们。

We will continue working closely with the FDA to bring this potential first tumor agnostic HER2 targeted medicine to patients as quickly as possible.”.

我们将继续与FDA密切合作，尽快将这种潜在的第一种不可知肿瘤的HER2靶向药物带给患者。”。

About DESTINY-PanTumor02

关于DESTINY-PanTumor02

DESTINY-PanTumor02 is a global, multicenter, multi-cohort, open-label phase 2 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) for the treatment of previously treated HER2 expressing tumors, including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic cancer or other tumors.

DESTINY-PanTumor02是一项全球性，多中心，多队列，开放标签的2期临床试验，评估ENHERTU（5.4 mg/kg）治疗先前治疗过的表达HER2的肿瘤的疗效和安全性，包括胆道，膀胱，宫颈，子宫内膜，卵巢癌，胰腺癌或其他肿瘤。

The primary efficacy endpoint of DESTINY-PanTumor02 is confirmed objective response rate (ORR) as assessed by investigator. Secondary endpoints include duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, tolerability and pharmacokinetics.

DESTINY-PanTumor02的主要疗效终点是由研究者评估的客观缓解率（ORR）。次要终点包括反应持续时间（DOR），疾病控制率（DCR），无进展生存期（PFS），总生存期（OS），安全性，耐受性和药代动力学。

DESTINY-PanTumor02 enrolled 267 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov..

DESTINY-PanTumor02在亚洲，欧洲和北美的多个地点招募了267名患者。有关该试验的更多信息，请访问ClinicalTrials.gov。。

The primary analysis of this study was presented in a late-breaking mini-oral session at the 2023 European Society for Medical Oncology (ESMO) Congress and simultaneously published in the Journal of Clinical Oncology.

这项研究的主要分析发表在2023年欧洲肿瘤内科学会（ESMO）大会上的一次小型口腔会议上，并同时发表在《临床肿瘤学杂志》上。

About DESTINY-Lung01

关于DESTINY-Lung01

DESTINY-Lung01 is a global phase 2, open-label, two-cohort trial evaluating the efficacy and safety of ENHERTU (6.4 mg/kg and 5.4 mg/kg) in patients with HER2 mutant (cohort 2, n=91) or HER2 overexpressing (cohort 1 and 1a, n=90) (defined as IHC 3+ or IHC 2+) unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) who had progressed after one or more systemic therapies.

DESTINY-Lung01是一项全球2期开放标签双队列试验，评估了ENHERTU（6.4 mg/kg和5.4 mg/kg）对HER2突变（队列2，n=91）或HER2过表达（队列1和1a，n=90）（定义为IHC 3+或IHC 2+）在一种或多种全身治疗后进展的不可切除或转移性非鳞状非小细胞肺癌（NSCLC）患者的疗效和安全性。

The primary endpoint is confirmed ORR by independent central review. Key secondary endpoints include DOR, DCR, PFS, OS and safety. DESTINY-Lung01 enrolled 181 patients at multiple sites, including Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov..

主要终点由独立的中央审查确认ORR。关键的次要终点包括DOR，DCR，PFS，OS和安全性。DESTINY-Lung01在多个地点招募了181名患者，包括亚洲，欧洲和北美。有关该试验的更多信息，请访问ClinicalTrials.gov。。

Full results from the HER2 mutant cohort were presented at the 2021 ESMO Congress and simultaneously published in The New England Journal of Medicine. Updated results from both cohorts of DESTINY-Lung01 were presented at the 2022 ESMO Congress.

HER2突变队列的完整结果已在2021年ESMO大会上发表，并同时发表在《新英格兰医学杂志》上。来自DESTINY-Lung01两个队列的最新结果在2022年ESMO大会上发表。

About DESTINY-CRC02

关于DESTINY-CRC02

DESTINY-CRC02 is a global, randomized, two arm, parallel, multicenter phase 2 trial evaluating the efficacy and safety of two doses (5.4 mg/kg or 6.4 mg/kg) of ENHERTU in patients with locally advanced, unresectable or metastatic HER2 positive colorectal cancer of BRAF wild-type, or RAS wild-type and RAS mutant tumor types previously treated with standard therapy.

DESTINY-CRC02是一项全球性，随机，双臂，平行，多中心的2期临床试验，评估两种剂量（5.4 mg/kg或6.4 mg/kg）的ENHERTU对局部晚期，不可切除或转移性HER2阳性BRAF野生型结直肠癌或RAS野生型和RAS突变型结直肠癌患者的疗效和安全性。

The trial was conducted in two stages. In the first stage, patients (n=80) were randomized 1:1 to receive either 5.4 mg/kg or 6.4 mg/kg of ENHERTU. In the second stage, additional patients (n=42) were enrolled in the 5.4 mg/kg arm. The primary endpoint is confirmed ORR as assessed by blinded independent central review.

试验分两个阶段进行。在第一阶段，患者（n=80）以1:1的比例随机接受5.4 mg/kg或6.4 mg/kg的ENHERTU。在第二阶段，另外的患者（n=42）被纳入5.4 mg/kg组。主要终点是通过盲法独立中央审查评估的ORR。

Secondary endpoints include DOR, DCR, investigator-assessed confirmed ORR, clinical benefit ratio, PFS, OS and safety. DESTINY-CRC02 enrolled 122 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov..

次要终点包括DOR，DCR，研究者评估的确诊ORR，临床获益率，PFS，OS和安全性。DESTINY-CRC02在亚洲，欧洲和北美的多个地点招募了122名患者。有关该试验的更多信息，请访问ClinicalTrials.gov。。

Primary results from the DESTINY-CRC02 phase 2 trial were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

DESTINY-CRC02 2期临床试验的主要结果发表在2023年美国临床肿瘤学会（ASCO）年会上。

About HER2 Expression in Solid Tumors

关于HER2在实体瘤中的表达

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.1,2 In some cancers, HER2 expression is amplified or the cells have activating mutations.1,3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis.4 While HER2 directed therapies have been used to treat breast, gastric, lung and colorectal cancers, more research is needed evaluating their potential role in treating other HER2 expressing solid tumor types.2,5,6.

HER2是一种酪氨酸激酶受体生长促进蛋白，在全身各种组织细胞表面表达，并参与正常细胞生长。1,2在某些癌症中，HER2表达被扩增或细胞具有激活突变。1,3 HER2蛋白过表达可能是HER2基因扩增的结果，通常与侵袭性疾病和预后不良有关。4虽然HER2定向疗法已被用于治疗乳腺癌，胃癌，肺癌和结直肠癌，需要更多的研究来评估它们在治疗其他表达HER2的实体瘤类型中的潜在作用[2,5,6]。

HER2 is an emerging biomarker in solid tumor types including biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers.3 Testing is not routinely performed in these additional tumor types and as a result, available literature is limited. In these solid tumors, HER2 positive expression, classified as IHC 3+, has been observed at rates from 1% to 28%.7,8.

HER2是实体瘤类型（包括胆道癌，膀胱癌，宫颈癌，子宫内膜癌，卵巢癌和胰腺癌）中新兴的生物标志物。3在这些其他肿瘤类型中不常规进行检测，因此，现有文献有限。在这些实体瘤中，HER2阳性表达（分类为IHC 3+）的发生率为1%〜28%[7,8]。

There is an unmet need for effective therapies for certain HER2 expressing solid tumors, particularly for those who have progressed on or are refractory to standard of care therapies as there are currently no approved HER2 directed therapies for these cancers.2,9

对于某些表达HER2的实体瘤，特别是对于那些已经进展或难以接受标准治疗的实体瘤，有效治疗的需求尚未得到满足，因为目前还没有批准的针对这些癌症的HER2定向治疗。2,9

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（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 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多个国家获得批准，用于治疗无法切除或转移性HER2阳性乳腺癌的成年患者，这些患者在转移性环境或新辅助或辅助性环境中接受过（或一种或多种）先前基于抗HER2的方案，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 45 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45多个国家获得批准，用于治疗无法切除或转移性HER2低（IHC 1+或IHC 2+/原位杂交（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，或在完成辅助化疗后的六个月内或六个月内复发DESTINY-Breast04测试。。

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）在全球30多个国家被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 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）在全球30多个国家被批准用于治疗局部晚期或转移性HER2阳性胃或胃食管交界处（GEJ）腺癌的成年患者，这些患者先前接受了基于曲妥珠单抗的方案，这些方案基于DESTINY-Gastric01和/或DESTINY-Gastric02试验的结果。。

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 (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 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）。。

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。

ENHERTU U.S. Important Safety Information

ENHERTU美国重要安全信息

Indications

适应症

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

ENHERTU是一种HER2定向抗体和拓扑异构酶抑制剂偶联物，用于治疗成年患者：

Unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either:

先前接受过抗HER2方案治疗的不可切除或转移性HER2阳性乳腺癌：

– In the metastatic setting, or

–在转移性环境中，或

– In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy

–在新辅助或辅助治疗中，并在完成治疗后的六个月内或六个月内出现疾病复发

Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy

根据FDA批准的测试确定，不可切除或转移性HER2低（IHC 1+或IHC 2+/ISH-）乳腺癌，这些患者先前在转移性环境中接受过化疗，或者在完成辅助化疗后6个月内或6个月内出现疾病复发

Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy

不可切除或转移的非小细胞肺癌（NSCLC），其肿瘤具有激活的HER2（ERBB2）突变，经FDA批准的测试检测，并且先前接受过全身治疗

This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

根据客观反应率和反应持续时间，加速批准该适应症。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。

Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen

先前接受过曲妥珠单抗治疗的局部晚期或转移性HER2阳性胃或胃食管交界处腺癌

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

警告：间质性肺病和胚胎-胎儿毒性

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis.

ENHERTU报道了间质性肺病（ILD）和肺炎，包括致命病例。监测并及时调查体征和症状，包括咳嗽、呼吸困难、发烧和其他新的或恶化的呼吸道症状。所有2级或更高ILD/肺炎患者永久停用ENHERTU。

Advise patients of the risk and to immediately report symptoms..

告知患者风险并立即报告症状。。

Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

怀孕期间接触ENHERTU会导致胚胎-胎儿伤害。告知患者这些风险以及有效避孕的必要性。

Contraindications

禁忌症

None.

没有。

Warnings and Precautions

警告和注意事项

Interstitial Lung Disease / Pneumonitis

间质性肺病/肺炎

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms.

用ENHERTU治疗的患者可能会发生严重，危及生命或致命的间质性肺病（ILD），包括肺炎。中度肾功能不全患者的1级和2级ILD/肺炎发生率较高。建议患者立即报告咳嗽、呼吸困难、发烧和/或任何新的或恶化的呼吸道症状。

Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose.

监测患者的ILD体征和症状。及时调查ILD的证据。通过放射成像评估疑似ILD的患者。考虑咨询肺科医生。对于无症状ILD/肺炎（1级），中断ENHERTU直至解决至0级，然后如果在发病日期≤28天内解决，则维持剂量。

If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks..

如果在发病日期后>28天内解决，则减少剂量一级。一旦怀疑ILD/肺炎（例如，≥0.5 mg/kg/天泼尼松龙或等效物），就考虑使用皮质类固醇治疗。对于有症状的ILD/肺炎（2级或更高），永久停用ENHERTU。一旦怀疑ILD/肺炎（例如，≥1 mg/kg/天泼尼松龙或同等药物），立即开始全身皮质类固醇治疗，并持续至少14天，然后逐渐减量至少4周。。

Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)

转移性乳腺癌和HER2突变NSCLC（5.4 mg/kg）

In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of patients treated with ENHERTU. Median time to first onset was 5 months (range: 0.9 to 23).

在用ENHERTU 5.4 mg/kg治疗的转移性乳腺癌和HER2突变NSCLC患者中，ILD发生率为12%。1.0%接受ENHERTU治疗的患者因ILD和/或肺炎而致命。首次发病的中位时间为5个月（范围：0.9至23）。

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

局部晚期或转移性胃癌（6.4 mg/kg）

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).

在用ENHERTU 6.4 mg/kg治疗的局部晚期或转移性HER2阳性胃腺癌或GEJ腺癌患者中，ILD发生率为10%。首次发病的中位时间为2.8个月（范围：1.2至21）。

Neutropenia

中性粒细胞减少

Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose.

用ENHERTU治疗的患者可能会出现严重的中性粒细胞减少症，包括发热性中性粒细胞减少症。在开始使用ENHERTU之前和每次给药之前以及根据临床指示监测全血细胞计数。对于3级中性粒细胞减少症（绝对中性粒细胞计数[ANC]<1.0至0.5 x 109/L），中断ENHERTU直至达到2级或更低，然后维持剂量。

For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by one level..

对于4级中性粒细胞减少症（ANC<0.5 x 109/L），中断ENHERTU直至达到2级或更低，然后将剂量减少一个水平。对于发热性中性粒细胞减少症（ANC<1.0 x 109/L，温度>38.3ºC或持续温度≥38ºC超过1小时），中断ENHERTU直至解决，然后将剂量减少一个水平。。

Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)

转移性乳腺癌和HER2突变NSCLC（5.4 mg/kg）

In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Sixteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 664).

在用ENHERTU 5.4 mg/kg治疗的转移性乳腺癌和HER2突变NSCLC患者中，据报道65%的患者中性粒细胞计数下降。16%的患者中性粒细胞计数降低了3或4级。中性粒细胞计数首次下降的中位时间为22天（范围：2至664）。

Febrile neutropenia was reported in 1.1% of patients..

据报道，1.1%的患者出现发热性中性粒细胞减少症。。

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

局部晚期或转移性胃癌（6.4 mg/kg）

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187).

在用ENHERTU 6.4 mg/kg治疗的局部晚期或转移性HER2阳性胃腺癌或GEJ腺癌患者中，据报道72%的患者中性粒细胞计数减少。51%的患者中性粒细胞计数降低了3或4级。中性粒细胞计数首次下降的中位时间为16天（范围：4至187）。

Febrile neutropenia was reported in 4.8% of patients..

据报道，4.8%的患者出现发热性中性粒细胞减少症。。

Left Ventricular Dysfunction

左心室功能不全

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated.

接受ENHERTU治疗的患者发生左心室功能障碍的风险可能会增加。用抗HER2疗法（包括ENHERTU）观察到左心室射血分数（LVEF）降低。根据临床指示，在开始ENHERTU之前和治疗期间定期评估LVEF。

Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks.

通过治疗中断管理LVEF降低。当LVEF>45%且从基线绝对下降10-20%时，继续用ENHERTU治疗。当LVEF为40-45%且从基线绝对下降小于10%时，继续使用ENHERTU治疗并在3周内重复LVEF评估。当LVEF为40-45%且从基线绝对下降为10-20%时，中断ENHERTU并在3周内重复LVEF评估。

If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks.

如果LVEF尚未从基线恢复到10%以内，则永久停用ENHERTU。如果LVEF从基线恢复到10%以内，则以相同剂量恢复用ENHERTU治疗。当LVEF小于40%或从基线绝对下降>20%时，中断ENHERTU并在3周内重复LVEF评估。

If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment..

如果LVEF小于40%或从基线绝对下降>20%，则永久停用ENHERTU。症状性充血性心力衰竭患者永久停用ENHERTU。在开始治疗之前，尚未对有临床显着心脏病史或LVEF<50%的患者进行ENHERTU治疗的研究。。

Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)

转移性乳腺癌和HER2突变NSCLC（5.4 mg/kg）

In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 3.6% of patients, of which 0.4% were Grade 3.

在用ENHERTU 5.4 mg/kg治疗的转移性乳腺癌和HER2突变NSCLC患者中，据报道3.6%的患者LVEF降低，其中0.4%为3级。

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

局部晚期或转移性胃癌（6.4 mg/kg）

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.

在用ENHERTU 6.4 mg/kg治疗的局部晚期或转移性HER2阳性胃腺癌或GEJ腺癌患者中，未报告心力衰竭的临床不良事件；然而，在超声心动图上，发现8%的LVEF无症状2级下降。

Embryo-Fetal Toxicity

胚胎-胎儿毒性

ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU.

给孕妇服用恩贺图会对胎儿造成伤害。告知患者胎儿的潜在风险。在ENHERTU开始之前，验证具有生殖潜力的女性的妊娠状况。建议有生殖潜力的女性在治疗期间和最后一剂ENHERTU后7个月内使用有效的避孕措施。

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU..

建议有生殖潜力的女性伴侣的男性患者在使用ENHERTU治疗期间和最后一剂ENHERTU后4个月内使用有效的避孕措施。。

Additional Dose Modifications

额外剂量修改

Thrombocytopenia

血小板减少症

For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by one level.

对于3级血小板减少症（血小板<50至25 x 109/L），中断ENHERTU直至达到1级或更低，然后维持剂量。对于4级血小板减少症（血小板<25 x 109/L），中断ENHERTU直至达到1级或更低，然后将剂量减少一个水平。

Adverse Reactions

不良反应

Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)

转移性乳腺癌和HER2突变NSCLC（5.4 mg/kg）

The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 984 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, and DESTINY-Lung02. Among these patients 65% were exposed for >6 months and 39% were exposed for >1 year.

汇总的安全人群反映了研究DS8201-A-J101（NCT02564900），DESTINY-Breast01，DESTINY-Breast03，DESTINY-Breast04和DESTINY-Lung02中984名患者每3周静脉注射5.4 mg/kg的ENHERTU。在这些患者中，65%暴露于>6个月，39%暴露于>1年。

In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (71%), decreased hemoglobin (66%), decreased neutrophil count (65%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (47%), increased aspartate aminotransferase (48%), vomiting (44%), increased alanine aminotransferase (42%), alopecia (39%), increased blood alkaline phosphatase (39%), constipation (34%), musculoskeletal pain (32%), decreased appetite (32%), hypokalemia (28%), diarrhea (28%), and respiratory infection (24%)..

在这个汇总的安全人群中，包括实验室异常在内的最常见（≥20%）的不良反应是恶心（76%），白细胞计数减少（71%），血红蛋白减少（66%），中性粒细胞计数减少（65%），淋巴细胞计数减少（55%），疲劳（54%），血小板计数减少（47%），天冬氨酸转氨酶增加（48%），呕吐（44%），丙氨酸氨基转移酶升高（42%），脱发（39%），血液碱性磷酸酶升高（39%），便秘（34%），肌肉骨骼疼痛（32%），食欲下降（32%），低钾血症（28%），腹泻（28%）和呼吸道感染（24%）。。

HER2-Positive Metastatic Breast Cancer

HER2阳性转移性乳腺癌

DESTINY-Breast03

The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg intravenously every three weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30).

在257例不可切除或转移性HER2阳性乳腺癌患者中评估了ENHERTU的安全性，这些患者在DESTINY-Breast03中每三周静脉注射至少一剂5.4 mg/kg的ENHERTU。中位治疗时间为14个月（范围：0.7至30）。

Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, interstitial lung disease, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (one patient each)..

接受ENHERTU治疗的患者中有19%发生严重不良反应。接受ENHERTU治疗的患者中，>1%的严重不良反应是呕吐，间质性肺病，肺炎，发热和尿路感染。0.8%的患者因不良反应死亡，包括新型冠状病毒肺炎和猝死（各一名患者）。。

ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis.

14%的患者永久停用ENHERTU，其中ILD/肺炎占8%。44%接受ENHERTU治疗的患者因不良反应而发生剂量中断。与剂量中断相关的最常见不良反应（>2%）是中性粒细胞减少症，白细胞减少症，贫血，血小板减少症，肺炎，恶心，疲劳和ILD/肺炎。

Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue..

21%接受ENHERTU治疗的患者剂量减少。与剂量减少相关的最常见不良反应（>2%）是恶心，中性粒细胞减少和疲劳。。

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), hypokalemia (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), respiratory infection (22%), headache (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%)..

最常见的（≥20%）不良反应包括实验室异常，包括恶心（76%），白细胞计数减少（74%），中性粒细胞计数减少（70%），天冬氨酸转氨酶增加（67%），血红蛋白减少（64%），淋巴细胞计数减少（55%），丙氨酸转氨酶增加（53%），血小板计数减少（52%），疲劳（49%），呕吐（49%），血液碱性磷酸酶升高（49%），脱发（37%），低钾血症（35%），便秘（34%），肌肉骨骼疼痛（31%），腹泻（29%），食欲下降（29%），呼吸道感染（22%），头痛（22%），腹痛（21%），血胆红素升高（20%）和口腔炎（20%）。。

HER2-Low Metastatic Breast Cancer

HER2低转移性乳腺癌

DESTINY-Breast04

The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU..

对371例不可切除或转移性HER2低（IHC 1+或IHC 2+/ISH-）乳腺癌患者进行了ENHERTU的安全性评估，这些患者每3周在DESTINY-Breast04中静脉注射ENHERTU 5.4 mg/kg。接受ENHERTU治疗的患者的中位治疗时间为8个月（范围：0.2至33）。。

Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each)..

接受ENHERTU治疗的患者中有28%发生严重不良反应。接受ENHERTU治疗的患者中，>1%的严重不良反应是ILD/肺炎，肺炎，呼吸困难，肌肉骨骼疼痛，败血症，贫血，发热性中性粒细胞减少症，高钙血症，恶心，发热和呕吐。包括ILD/肺炎（3例）在内的4%患者因不良反应死亡；败血症（2例）；和缺血性结肠炎，弥散性血管内凝血，呼吸困难，发热性中性粒细胞减少症，一般身体健康恶化，胸腔积液和呼吸衰竭（各1例）。。

ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia.

16%的患者永久停用ENHERTU，其中ILD/肺炎占8%。39%接受ENHERTU治疗的患者因不良反应而发生剂量中断。与剂量中断相关的最常见不良反应（>2%）是中性粒细胞减少症，疲劳，贫血，白细胞减少症，COVID-19，ILD/肺炎，转氨酶升高和高胆红素血症。

Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia..

23%接受ENHERTU治疗的患者剂量减少。与剂量减少相关的最常见不良反应（>2%）是疲劳，恶心，血小板减少和中性粒细胞减少。。

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and hypokalemia (25%)..

包括实验室异常在内的最常见（≥20%）的不良反应是恶心（76%），白细胞计数减少（70%），血红蛋白减少（64%），中性粒细胞计数减少（64%），淋巴细胞计数减少（55%），疲劳（54%），血小板计数减少（44%），脱发（40%），呕吐（40%），天冬氨酸转氨酶增加（38%），丙氨酸转氨酶增加（36%），便秘（34%），血液碱性磷酸酶升高（34%），食欲下降（32%），肌肉骨骼疼痛（32%），腹泻（27%）和低钾血症（25%）。。

Unresectable or Metastatic HER2-Mutant NSCLC (5.4 mg/kg)

不可切除或转移的HER2突变NSCLC（5.4 mg/kg）

DESTINY-Lung02 evaluated two dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis..

DESTINY-Lung02评估了两种剂量水平（5.4 mg/kg[n=101]和6.4 mg/kg[n=50]）；然而，由于在NSCLC患者（包括ILD/肺炎）中观察到较高剂量的毒性增加，因此每3周静脉注射推荐剂量5.4 mg/kg的结果如下所述。。

The safety of ENHERTU was evaluated in 101 patients with unresectable or metastatic HER2-mutant NSCLC who received ENHERTU 5.4 mg/kg intravenously every three weeks in DESTINY-Lung02. Nineteen percent of patients were exposed for >6 months.

在101例不可切除或转移的HER2突变NSCLC患者中评估了ENHERTU的安全性，这些患者在DESTINY-Lung02中每三周静脉注射ENHERTU 5.4 mg/kg。19%的患者暴露时间超过6个月。

Serious adverse reactions occurred in 30% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea, nausea, pleural effusion, and increased troponin I. Fatality occurred in 1 patient with suspected ILD/pneumonitis (1%)..

接受ENHERTU治疗的患者中有30%发生严重不良反应。接受ENHERTU治疗的患者中，>1%的严重不良反应为ILD/肺炎，血小板减少，呼吸困难，恶心，胸腔积液和肌钙蛋白I升高。1例疑似ILD/肺炎患者（1%）死亡。。

ENHERTU was permanently discontinued in 8% of patients. Adverse reactions which resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis, diarrhea, hypokalemia, hypomagnesemia, myocarditis, and vomiting. Dose interruptions of ENHERTU due to adverse reactions occurred in 23% of patients.

8%的患者永久停用ENHERTU。导致永久停用ENHERTU的不良反应是ILD/肺炎，腹泻，低钾血症，低镁血症，心肌炎和呕吐。23%的患者因不良反应而中断了ENHERTU的剂量。

Adverse reactions which required dose interruption (>2%) included neutropenia and ILD/pneumonitis. Dose reductions due to an adverse reaction occurred in 11% of patients..

需要中断剂量（>2%）的不良反应包括中性粒细胞减少症和ILD/肺炎。11%的患者因不良反应而减少剂量。。

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (61%), decreased white blood cell count (60%), decreased hemoglobin (58%), decreased neutrophil count (52%), decreased lymphocyte count (43%), decreased platelet count (40%), decreased albumin (39%), increased aspartate aminotransferase (35%), increased alanine aminotransferase (34%), fatigue (32%), constipation (31%), decreased appetite (30%), vomiting (26%), increased alkaline phosphatase (22%), and alopecia (21%)..

包括实验室异常在内的最常见（≥20%）不良反应是恶心（61%），白细胞计数减少（60%），血红蛋白减少（58%），中性粒细胞计数减少（52%），淋巴细胞计数减少（43%），血小板计数减少（40%），白蛋白减少（39%），天冬氨酸转氨酶增加（35%），丙氨酸转氨酶增加（34%），疲劳（32%），便秘（31%），食欲下降（30%），呕吐（26%），碱性磷酸酶升高（22%）和脱发（21%）。。

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

局部晚期或转移性胃癌（6.4 mg/kg）

The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks.

在DESTINY-Gastric01中，对187例局部晚期或转移性HER2阳性胃腺癌或GEJ腺癌患者评估了ENHERTU的安全性。患者每3周静脉注射至少一剂ENHERTU（N=125）6.4 mg/kg或伊立替康（N=55）150 mg/m2，每两周或紫杉醇（N=7）80 mg/m2，持续3周。

The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU..

接受ENHERTU治疗的患者的中位治疗时间为4.6个月（范围：0.7至22.3）。。

Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%)..

接受ENHERTU 6.4 mg/kg的患者中有44%发生严重不良反应。接受ENHERTU治疗的患者中，>2%的严重不良反应是食欲下降，ILD，贫血，脱水，肺炎，胆汁淤积性黄疸，发热和肿瘤出血。2.4%的患者因不良反应死亡：弥散性血管内凝血、大肠穿孔和肺炎各发生1例（0.8%）。。

ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia.

15%的患者永久停用ENHERTU，其中ILD占6%。62%接受ENHERTU治疗的患者因不良反应而发生剂量中断。与剂量中断相关的最常见不良反应（>2%）是中性粒细胞减少症，贫血，食欲下降，白细胞减少症，疲劳，血小板减少症，ILD，肺炎，淋巴细胞减少症，上呼吸道感染，腹泻和低钾血症。

Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia..

32%接受ENHERTU治疗的患者剂量减少。与剂量减少相关的最常见不良反应（>2%）是中性粒细胞减少症，食欲下降，疲劳，恶心和发热性中性粒细胞减少症。。

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%)..

包括实验室异常在内的最常见（≥20%）不良反应是血红蛋白降低（75%），白细胞计数降低（74%），中性粒细胞计数降低（72%），淋巴细胞计数降低（70%），血小板计数降低（68%），恶心（63%），食欲下降（60%），天冬氨酸转氨酶升高（58%），疲劳（55%），血液碱性磷酸酶升高（54%），丙氨酸转氨酶升高（47%），腹泻（32%），低钾血症（30%），呕吐（26%），便秘（24%），血胆红素升高（24%），发热（24%）和脱发（22%）。。

Use in Specific Populations

在特定人群中使用

Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU.

怀孕：恩贺图给孕妇服用时会对胎儿造成伤害。告知患者胎儿的潜在风险。如果孕妇使用ENHERTU，或者患者在最后一剂ENHERTU后7个月内怀孕，则有临床考虑因素。

Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose..

哺乳期：没有关于母乳中ENHERTU的存在，对母乳喂养的孩子的影响或对产奶量的影响的数据。由于母乳喂养的孩子可能会产生严重的不良反应，因此建议女性在使用ENHERTU治疗期间以及最后一次服用后7个月内不要母乳喂养。。

Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose.

生殖潜能的女性和男性：妊娠测试：在开始ENHERTU之前验证生殖潜能女性的妊娠状况。避孕方法：女性：ENHERTU给孕妇服用时会对胎儿造成伤害。建议有生殖潜力的女性在使用ENHERTU治疗期间和最后一剂后7个月内使用有效的避孕方法。

Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair male reproductive function and fertility..

男性：建议有生殖潜力的女性伴侣的男性患者在使用ENHERTU治疗期间和最后一剂后4个月内使用有效的避孕方法。不育症：ENHERTU可能会损害男性的生殖功能和生育能力。。

Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.

儿科使用：ENHERTU的安全性和有效性尚未在儿科患者中确定。

Geriatric Use: Of the 883 patients with breast cancer treated with ENHERTU 5.4 mg/kg, 22% were ≥65 years and 3.6% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (60%) as compared to younger patients (48%).

老年使用：在用ENHERTU 5.4 mg/kg治疗的883例乳腺癌患者中，22%的患者≥65岁，3.6%的患者≥75岁。与年轻患者相比，≥65岁的患者在临床研究中没有观察到总体疗效差异。与年轻患者（48%）相比，≥65岁患者（60%）观察到的3-4级不良反应发生率更高。

Of the 101 patients with unresectable or metastatic HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, 40% were ≥65 years and 8% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years.

在用ENHERTU 5.4 mg/kg治疗的101例不可切除或转移性HER2突变NSCLC患者中，40%的患者≥65岁，8%的患者≥75岁。与年轻患者相比，≥65岁的患者在疗效或安全性方面没有观察到总体差异。在DESTINY-Gastric01中用ENHERTU 6.4 mg/kg治疗的125例局部晚期或转移性HER2阳性胃腺癌或GEJ腺癌患者中，56%≥65岁，14%≥75岁。

No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients..

与年轻患者相比，≥65岁的患者在疗效或安全性方面没有总体差异。。

Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min)..

肾功能不全：中度肾功能不全患者的1级和2级ILD/肺炎发生率较高。更频繁地监测中度肾功能不全患者。对于严重肾功能不全（CLcr<30 mL/min）的患者，尚未确定ENHERTU的推荐剂量。。

Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST)..

肝损伤：对于中度肝损伤患者，由于可能增加暴露，密切监测与拓扑异构酶抑制剂相关的毒性增加。对于严重肝功能损害（总胆红素>3倍ULN和任何AST）的患者，尚未确定ENHERTU的推荐剂量。。

To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

要报告疑似不良反应，请联系Daiichi Sankyo，Inc.，电话1-877-437-7763或FDA，电话1-800-FDA-1088或FDA.gov/medwatch。

Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

请参阅随附的完整处方信息，包括盒装警告和药物指南。

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。

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

欲了解更多信息，请访问www.daiichisankyo.com。。

References:

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2 Iqbal N等人，MolInt.2014；852748.

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3 Omar N等人。发病机理。2015年；2（3）：1-9。

4 Pillai R, et al. Cancer. 2017;1;123(21): 4099-4105.