BASKING RIDGE, N.J. & RAHWAY, N.J.--(BUSINESS WIRE)--The U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) seeking accelerated approval of Daiichi Sankyo (TSE: 4568) and Merck’s (known as MSD outside of the United States and Canada) (NYSE: MRK) patritumab deruxtecan (HER3-DXd) for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) previously treated with two or more systemic therapies..

新泽西州BASKING RIDGE和新泽西州RAHWAY——（商业新闻短讯）——美国食品和药物管理局（FDA）已就生物制剂许可证申请（BLA）发布了一份完整的回复函（CRL），寻求加速批准Daiichi Sankyo（TSE:4568）和Merck（在美国和加拿大以外称为MSD）（纽约证券交易所：MRK）patritumab deruxtecan（HER3 DXd），用于治疗先前接受过两种或两种以上全身治疗的局部晚期或转移性EGFR突变非小细胞肺癌（NSCLC）成年患者。。

The CRL results from findings pertaining to an inspection of a third-party manufacturing facility. The CRL did not identify any issues with the efficacy or safety data submitted.

CRL是根据与第三方制造设施检查有关的发现得出的。CRL没有发现提交的疗效或安全性数据有任何问题。

Patritumab deruxtecan is a specifically engineered potential first-in-class HER3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and Merck.

Patritumab deruxtecan是由Daiichi Sankyo发现并由Daiichi Sankyo和Merck联合开发的具有特殊工程潜力的一流HER3定向DXd抗体-药物偶联物（ADC）。

“We will work closely with the FDA and the third-party manufacturer to address the feedback as quickly as possible in order to bring the first HER3 directed medicine to patients with previously-treated EGFR-mutated non-small cell lung cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo.

“我们将与FDA和第三方制造商密切合作，尽快解决反馈问题，以便为先前接受过EGFR突变的非小细胞肺癌治疗的患者提供第一种针对HER3的药物，”第一三共研发全球负责人Ken Takeshita医学博士说。

“We remain confident in the ability to develop this medicine to its full potential.”.

“我们仍然有信心充分发挥这种药物的潜力。”。

“Patients with previously treated EGFR-mutated non-small cell lung cancer often experience recurrence and have limited treatment options,” said Marjorie Green, MD, Senior Vice President and Head of Oncology, Global Clinical Development, Merck Research Laboratories. “We are committed to working with Daiichi Sankyo and the FDA to prioritize bringing patritumab deruxtecan to these patients in need.”.

默克研究实验室全球临床开发高级副总裁兼肿瘤学主管Marjorie Green医学博士说：“先前接受过EGFR突变的非小细胞肺癌治疗的患者经常会复发，治疗选择有限。”。“我们致力于与第一三共和FDA合作，优先将patritumab deruxtecan带给这些有需要的患者。”。

The BLA is based on the primary results from the HERTHENA-Lung01 pivotal phase 2 trial that were presented at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) and simultaneously published in the Journal of Clinical Oncology.

BLA基于HERTHENA-Lung01关键性2期试验的主要结果，该试验在IASLC 2023年世界肺癌会议（WCLC23）上发表，并同时发表在《临床肿瘤学杂志》上。

In HERTHENA-Lung01, patritumab deruxtecan was studied in 225 patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy, which demonstrated an objective response rate (ORR) of 29.8% (95% CI: 23.9-36.2), including one complete response and 66 partial responses.

在HERTHENA-Lung01中，对225例EGFR突变的局部晚期或转移性NSCLC患者进行了EGFR TKI和铂类化疗后的客观缓解率（ORR）为29.8%（95%CI:23.9-36.2），包括一个完全缓解和66个部分缓解。

The median duration of response (DoR) was 6.4 months (95% CI: 4.9-7.8)..

中位缓解时间（DoR）为6.4个月（95%CI:4.9-7.8）。。

The safety profile of patritumab deruxtecan observed in HERTHENA-Lung01 was consistent with previous phase 1 clinical trials in NSCLC with a treatment discontinuation rate of 7.1% due to treatment-emergent adverse events (TEAEs). Grade 3 or higher TEAEs occurred in 64.9% of patients. The most common (≥5%) grade 3 or higher TEAEs were thrombocytopenia (21%), neutropenia (19%), anemia (14%), leukopenia (10%), fatigue (6%), hypokalemia (5%) and asthenia (5%).

在HERTHENA-Lung01中观察到的patritumab deruxtecan的安全性与之前的NSCLC 1期临床试验一致，由于治疗紧急不良事件（TEAE），治疗中断率为7.1%。64.9%的患者发生3级或更高的TEAE。最常见（≥5%）的3级或更高TEAE是血小板减少症（21%），中性粒细胞减少症（19%），贫血（14%），白细胞减少症（10%），疲劳（6%），低钾血症（5%）和虚弱（5%）。

Twelve patients (5.3%) had confirmed treatment-related interstitial lung disease (ILD) as determined by an independent adjudication committee. One grade 5 ILD event was observed..

由独立裁决委员会确定，12名患者（5.3%）已确诊与治疗相关的间质性肺病（ILD）。观察到一次5级ILD事件。。

About HERTHENA-Lung01

关于HERTHENA-Lung01

HERTHENA-Lung01 is a global, multicenter, open-label, two-arm phase 2 trial evaluating the safety and efficacy of patritumab deruxtecan in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy. Patients were randomized 1:1 to receive 5.6 mg/kg (n=225) or an uptitration regimen (n=50).

HERTHENA-Lung01是一项全球性，多中心，开放标签的双臂2期临床试验，评估了patritumab deruxtecan在EGFR突变的局部晚期或转移性NSCLC患者中使用EGFR TKI和铂类化疗后的安全性和有效性。患者以1:1的比例随机接受5.6 mg/kg（n=225）或上调方案（n=50）。

The uptitration arm was discontinued as the dose of 5.6 mg/kg of patritumab deruxtecan was selected following a risk-benefit analysis conducted from the phase 1 trial assessing the doses in a similar patient population..

由于在评估类似患者人群剂量的第一阶段试验中进行了风险-收益分析，选择了5.6 mg/kg的patritumab deruxtecan剂量，因此停用了上调组。。

The primary endpoint of HERTHENA-Lung01 was ORR as assessed by blinded independent central review (BICR). Secondary endpoints included DoR, progression-free survival, disease control rate, and time to response – all assessed by both BICR and investigator assessment – as well as investigator-assessed ORR, overall survival, safety and tolerability..

HERTHENA-Lung01的主要终点是ORR，由盲法独立中央审查（BICR）评估。次要终点包括DoR，无进展生存期，疾病控制率和反应时间-所有这些都通过BICR和研究者评估评估-以及研究者评估的ORR，总生存期，安全性和耐受性。。

HERTHENA-Lung01 enrolled patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov.

HERTHENA-Lung01在亚洲，欧洲，北美和大洋洲招募了患者。有关该试验的更多信息，请访问ClinicalTrials.gov。

About EGFR-Mutated Non-Small Cell Lung Cancer

关于EGFR突变的非小细胞肺癌

Approximately 226,000 lung cancer cases were diagnosed in the U.S. in 2022.1 Lung cancer is the third most common cancer and the leading cause of cancer-related deaths in the U.S.1 NSCLC accounts for approximately 81% of all lung cancers in the U.S., with 52% having distant spread at diagnosis.2,3 EGFR mutations occur in approximately one in five patients with NSCLC in Western populations.4.

2022年，美国诊断出约226000例肺癌病例。肺癌是美国第三大常见癌症，也是美国癌症相关死亡的主要原因。NSCLC约占美国所有肺癌的81%，其中52%在诊断时有远处扩散。2,3 EGFR突变发生在西方人群中约五分之一的NSCLC患者中。

About HER3

关于HER3

HER3 is a member of the EGFR family of receptor tyrosine kinases.5 It is estimated that about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors express HER3 after prior EGFR TKI treatment.6,7 HER3 is associated with poor treatment outcomes, including shorter relapse-free survival and significantly reduced survival.8,9 There is currently no HER3 directed therapy approved for the treatment of any cancer..

HER3是受体酪氨酸激酶EGFR家族的成员[5]。据估计，大约83%的原发性NSCLC肿瘤和90%的晚期EGFR突变肿瘤在先前的EGFR TKI治疗后表达HER3[6,7]。HER3与不良治疗结果相关，包括较短的无复发生存期和显着降低的生存率[8,9]。目前还没有HER3定向治疗被批准用于治疗任何癌症。。

About Patritumab Deruxtecan

关于Patritumab Deruxtecan

Patritumab deruxtecan (HER3-DXd) is an investigational HER3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, patritumab deruxtecan is composed of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers..

Patritumab deruxtecan（HER3 DXd）是一种研究性HER3指导的ADC。patritumab deruxtecan是使用Daiichi Sankyo专有的DXd ADC技术设计的，它由一种全人抗HER3 IgG1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（一种exatecan衍生物DXd）上。。

Patritumab deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration in December 2021 for the treatment of patients with EGFR-mutated locally advanced or metastatic NSCLC with disease progression on or after treatment with a third-generation TKI and platinum-based therapies..

Patritumab deruxtecan于2021年12月被美国食品和药物管理局授予突破性治疗指定，用于治疗EGFR突变的局部晚期或转移性NSCLC患者，这些患者在使用第三代TKI和铂类疗法治疗时或治疗后疾病进展。。

Patritumab deruxtecan is currently being evaluated as both a monotherapy and in combination with other therapies in a global development program, which includes HERTHENA-Lung02, a phase 3 trial evaluating the efficacy and safety of patritumab deruxtecan versus platinum-based chemotherapy in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression on or after treatment with a third-generation EGFR TKI; HERTHENA-Lung01, a phase 2 trial in metastatic or locally advanced NSCLC with an activating EGFR mutation previously treated with at least one EGFR TKI and one platinum-based chemotherapy-containing regimen; HERTHENA-PanTumor01, a phase 2 trial in locally advanced or metastatic solid tumors, including melanoma, gastric and head and neck cancer, among other types of cancer, previously treated with at least one prior systemic therapy; a phase 1 trial in combination with osimertinib in EGFR-mutated locally advanced or metastatic NSCLC; and a phase 1 trial in previously treated patients with advanced NSCLC.

Patritumab deruxtecan目前正在全球发展计划中被评估为单一疗法，并与其他疗法联合使用，该计划包括HERTHENA-Lung02，这是一项评估Patritumab deruxtecan与铂类化疗对EGFR突变的局部晚期或转移性NSCLC患者的疗效和安全性的3期试验，在用第三代EGFR TKI治疗或治疗后疾病进展；HERTHENA-Lung01是一项转移性或局部晚期NSCLC的2期临床试验，其具有激活的EGFR突变，先前已用至少一种EGFR TKI和一种含铂类化疗方案治疗；HERTHENA-PanTumor01是一项针对局部晚期或转移性实体瘤的2期临床试验，包括黑色素瘤，胃癌和头颈癌以及其他类型的癌症，之前至少接受过一次全身治疗；联合osimertinib治疗EGFR突变的局部晚期或转移性NSCLC的1期临床试验；以及先前治疗的晚期非小细胞肺癌患者的1期临床试验。

A phase 1/2 trial in HER3 expressing metastatic breast cancer also has been completed..

表达HER3的转移性乳腺癌的1/2期试验也已完成。。

About the Daiichi Sankyo and Merck Collaboration

关于第一三共和默克的合作

Daiichi Sankyo and Merck entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply..

2023年10月，第一三共与默克公司达成全球合作，共同开发和商业化patritumab deruxtecan（HER3 DXd）、ifinatamab deruxtecan（I-DXd）和raludotatug deruxtecan（R-DXd），但在日本，第一三共将保留专有权。第一三共将全权负责制造和供应。。

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.

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，正在与默克公司联合开发和全球商业化。

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

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。

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 needs.

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。。

Merck’s Focus on Cancer

默克专注于癌症

Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms.

每天，我们都在遵循科学，努力发现可以帮助患者的创新，无论他们处于癌症的哪个阶段。作为一家领先的肿瘤学公司，我们正在寻求科学机会和医疗需求相融合的研究，并以我们超过25种新型机制的多样化渠道为基础。

With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care.

凭借跨越30多种肿瘤类型的最大临床开发项目之一，我们努力推进突破性科学，这将塑造肿瘤学的未来。通过解决临床试验参与，筛查和治疗的障碍，我们迫切需要减少差异，并帮助确保患者获得高质量的癌症护理。

Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology/..

我们坚定不移的承诺将使我们更接近为更多癌症患者带来生命的目标。有关更多信息，请访问https://www.merck.com/research/oncology/..

About Merck

默克

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines.

在美国和加拿大以外被称为MSD的默克公司，我们的目标是团结一致的：我们利用尖端科学的力量来拯救和改善世界各地的生活。130多年来，我们通过开发重要的药物和疫苗给人类带来了希望。

We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities.

我们立志成为世界上领先的研究密集型生物制药公司，今天，我们处于研究的前沿，以提供创新的健康解决方案，促进人类和动物疾病的预防和治疗。我们培养了一支多元化和包容性的全球劳动力队伍，并每天负责任地运作，为所有人和社区创造一个安全、可持续和健康的未来。

For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn..

有关更多信息，请访问www.merck.com，并通过X（以前的Twitter）、Facebook、Instagram、YouTube和LinkedIn与我们联系。。

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

美国新泽西州拉赫韦默克公司的前瞻性声明

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties.

美国新泽西州拉赫韦市默克公司（以下简称“公司”）的本新闻稿包括1995年《美国私人证券诉讼改革法案》安全港条款所指的“前瞻性声明”。这些声明基于公司管理层当前的信念和期望，并且存在重大风险和不确定性。

There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements..

对于管道候选人，不能保证候选人将获得必要的监管批准，或者证明他们在商业上取得了成功。如果基础假设不准确或风险或不确定性具体化，实际结果可能与前瞻性声明中规定的结果存在重大差异。。

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions..

风险和不确定性包括但不限于一般行业条件和竞争；一般经济因素，包括利率和货币汇率波动；美国和国际上制药行业法规和医疗保健立法的影响；医疗保健成本控制的全球趋势；竞争对手取得的技术进步、新产品和专利；新产品开发固有的挑战，包括获得监管部门的批准；公司准确预测未来市场状况的能力；制造困难或延误；国际经济金融不稳定和主权风险；依赖公司专利和其他创新产品保护的有效性；以及诉讼风险，包括专利诉讼和/或监管行动。。

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2023 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov)..

公司没有义务公开更新任何前瞻性声明，无论是由于新信息、未来事件还是其他原因。可能导致结果与前瞻性声明中描述的结果产生重大差异的其他因素可以在公司截至2023年12月31日的10-K表年度报告以及公司向证券交易委员会（SEC）提交的其他文件中找到，这些文件可在SEC的互联网网站（www.SEC.gov）上找到。。

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References:

参考文献：

1 World Health Organization. International Agency for Research on Cancer. U.S. Cancer Fact Sheet. Accessed June 2024.

1世界卫生组织。国际癌症研究机构。U、 美国癌症概况。2024年6月访问。

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