Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the Phase 3 KEYNOTE-689 trial evaluating KEYTRUDA

默克公司（纽约证券交易所代码：MRK），在美国和加拿大以外地区以MSD之名运营，今天公布了评估KEYTRUDA的3期KEYNOTE-689试验结果。

(pembrolizumab), Merck’s anti-PD-1 therapy, as a perioperative treatment regimen for patients with stage III or IVA, resected, locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Results at the first interim analysis of the trial showed KEYTRUDA significantly improved event-free survival (EFS) as part of a perioperative treatment regimen with adjuvant standard of care (SOC) radiotherapy with or without cisplatin compared to adjuvant standard of care (SOC) radiotherapy with or without cisplatin alone in patients with resectable LA-HNSCC.

默克公司的抗PD-1疗法（pembrolizumab），作为围手术期治疗方案，用于III期或IVA期、已切除的局部晚期头颈部鳞状细胞癌（LA-HNSCC）患者。试验的首次中期分析结果显示，在可切除的LA-HNSCC患者中，与单独使用辅助标准治疗（SOC）放疗加或不加顺铂相比，KEYTRUDA作为围手术期治疗方案联合辅助标准治疗（SOC）放疗加或不加顺铂显著改善了无事件生存期（EFS）。

These data are being presented for the first time today during a Plenary Session at the American Association for Cancer Research (AACR) Annual Meeting 2025 (Abstract #CT001) and were selected for the AACR press program..

这些数据今天首次在 2025 年美国癌症研究协会 (AACR) 年会的全体会议上公布（摘要编号 #CT001），并入选 AACR 新闻计划。

After a median follow-up of 38.3 months (range, 9.0-66.5), treatment with KEYTRUDA before surgery (neoadjuvant), then continued in combination with standard of care radiotherapy (with or without cisplatin) after surgery followed by KEYTRUDA alone (adjuvant), reduced the risk of EFS events by 34% (HR=0.66 [95% CI, 0.49-0.88]; p=.0022) in the combined positive score (CPS) ≥10 population, by 30% (HR=0.70 [95% CI, 0.55-0.89; p=.0014) in the CPS ≥1 population and by 27% (HR=0.73 [95% CI 0.58-0.92]; p=.0041) in the intent-to-treat (ITT) population, compared to adjuvant radiotherapy (with or without cisplatin) alone in the ITT population.

在中位随访38.3个月（范围9.0-66.5）后，术前使用KEYTRUDA（新辅助治疗），术后继续联合标准放疗（含或不含顺铂）并随后单独使用KEYTRUDA（辅助治疗），在合并阳性评分（CPS）≥10人群中将无事件生存期（EFS）事件风险降低了34%（HR=0.66 [95% CI, 0.49-0.88]; p=.0022），在CPS ≥1人群中降低了30%（HR=0.70 [95% CI, 0.55-0.89]; p=.0014），在意向治疗（ITT）人群中降低了27%（HR=0.73 [95% CI 0.58-0.92]; p=.0041），相比仅在ITT人群中使用辅助放疗（含或不含顺铂）。

Among the CPS ≥10 population, median EFS was 59.7 months in the KEYTRUDA plus SOC group (95% CI, 41.1-not reached) versus 26.9 months (95% CI, 18.3-51.5) in the SOC group. Among the CPS ≥1 population, median EFS was 59.7 months (95% CI, 37.9-not reached) in the KEYTRUDA plus SOC group versus 29.6 months (95% CI, 19.5-41.9) in the SOC group.

在CPS ≥10人群中，KEYTRUDA联合SOC组的中位EFS为59.7个月（95% CI，41.1-未达到），而SOC组为26.9个月（95% CI，18.3-51.5）。在CPS ≥1人群中，KEYTRUDA联合SOC组的中位EFS为59.7个月（95% CI，37.9-未达到），而SOC组为29.6个月（95% CI，19.5-41.9）。

In the ITT population, median EFS was 51.8 months (95% CI, 37.5-not reached) in the KEYTRUDA plus SOC group versus 30.4 months (95% CI, 21.8-50.1) in the SOC group. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were identified..

在ITT人群中，KEYTRUDA加SOC组的中位EFS为51.8个月（95% CI，37.5-未达到），而SOC组为30.4个月（95% CI，21.8-50.1）。KEYTRUDA的安全性与其在先前研究报告中观察到的一致；未发现新的安全性信号。

“As the first positive trial in over two decades for patients with resectable, locally advanced head and neck squamous cell carcinoma, the presentation of these landmark results marks an important moment for these patients and those who care for them,” said Dr. Ravindra Uppaluri, the study’s co-principal investigator, director of Head and Neck Surgical Oncology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute.

“作为二十多年来针对可切除的局部晚期头颈部鳞状细胞癌患者的首个阳性试验，这些具有里程碑意义的结果的发布标志着对这些患者以及照顾他们的人来说是一个重要的时刻，”该研究的共同首席研究员、布里格姆妇女医院和丹娜法伯癌症研究所头颈外科肿瘤学主任拉温德拉·乌帕卢里博士表示。

“KEYNOTE-689 represents a meaningful development with a potential to provide an option that helps certain patients with LA-HNSCC reduce the risk of recurrence and disease progression earlier in their treatment journey.”.

“KEYNOTE-689 代表了一项有意义的进步，有可能为某些 LA-HNSCC 患者提供一种选择，帮助他们在治疗早期降低复发和疾病进展的风险。”

“The addition of immunotherapy using KEYTRUDA to standard of care surgery and adjuvant (chemo)radiotherapy resulted in a significant reduction in the risk of event-free survival events by 27%, compared with standard of care therapy alone,” said study co-principal investigator Dr. Douglas Adkins, Professor, Division of Oncology, Washington University School of Medicine in St.

“与单独使用标准护理疗法相比，将KEYTRUDA免疫疗法加入标准护理手术和辅助（化疗）放疗中，使得无事件生存事件的风险显著降低了27%，”该研究的共同首席研究员、华盛顿大学医学院肿瘤学系教授道格拉斯·阿德金斯博士表示。

Louis. “These results are notable as they mark the first time an anti-PD-1 therapy has demonstrated a statistically significant and clinically meaningful improvement in event-free survival in the neoadjuvant and adjuvant setting in earlier stages of head and neck squamous cell carcinoma.”.

路易斯。“这些结果值得注意，因为它们标志着抗PD-1疗法首次在头颈部鳞状细胞癌的早期阶段的新辅助和辅助治疗中显示出具有统计学意义和临床意义的无事件生存改善。”

The study also showed a statistically significant improvement in major pathological response (mPR) rate, a key secondary endpoint, in patients with CPS ≥10 (difference in mPR rates: 13.7% [95% CI, 9.7-18.7]; p<0.00001), CPS ≥1 (9.8% [95% CI, 7.0-13.3]; p<0.00001) and in the ITT population (9.3% [95% CI, 6.7–12.8, P<.00001), compared to adjuvant radiotherapy alone..

研究还显示，在CPS≥10（mPR率差异：13.7% [95% CI，9.7-18.7]；p<0.00001）、CPS≥1（9.8% [95% CI，7.0-13.3]；p<0.00001）以及意向治疗（ITT）人群（9.3% [95% CI，6.7–12.8，P<.00001）中，主要病理缓解（mPR）率这一关键次要终点均有统计学显著改善，相较于单独的辅助放疗。

A trend toward improvement in overall survival (OS), another key secondary endpoint, was observed in patients with CPS ≥10 (HR=0.72 [95% CI, 0.52-0.98])

在CPS ≥10的患者中观察到总生存期（OS）这一关键次要终点有改善趋势（HR=0.72 [95% CI, 0.52-0.98]）。

at the time of this interim analysis for the KEYTRUDA plus standard of care regimen versus standard of care alone. The OS results did not reach statistical significance at the time of this interim analysis. Due to the statistical testing hierarchy, formal testing was not performed in the CPS ≥1 and ITT populations.

在本次对KEYTRUDA联合标准治疗方案与单独标准治疗的中期分析时，总生存期（OS）结果未达到统计学显著性。由于统计检验的层级关系，未在CPS ≥1和意向治疗（ITT）人群中进行正式检验。

OS will be evaluated at the next interim analysis..

操作系统将在下一次中期分析时进行评估。

positive pivotal trial for a KEYTRUDA-based regimen in earlier-stage cancers, the results from KEYNOTE-689 are a testament to our commitment to address an unmet need in this important area of research,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories.

“KEYNOTE-689的积极关键试验结果证明了我们致力于满足这一重要研究领域中未被满足的需求，”默克研究实验室肿瘤学高级副总裁兼全球临床开发主管马乔里·格林博士说道。

“These compelling results illustrate the potential of this regimen to change the landscape of care for certain patients facing this challenging disease. We are working with the FDA and other global authorities to bring this new option to patients as quickly as possible.”.

“这些令人信服的结果展示了该方案在改变某些面临这一棘手疾病的患者的治疗前景方面的潜力。我们正在与FDA及其他全球监管机构合作，尽快将这一新选择带给患者。”

supplemental Biologics License Application (sBLA)

补充生物制品许可申请 (sBLA)

for KEYTRUDA based on data from KEYNOTE-689 is under priority review with the U.S. Food and Drug Administration (FDA), with a Prescription Drug User Fee Act (PDUFA), or target action, date of June 23, 2025.

基于KEYNOTE-689试验数据的KEYTRUDA正在接受美国食品药品监督管理局（FDA）的优先审查，处方药用户费用法案（PDUFA）或目标行动日期为2025年6月23日。

KEYTRUDA is currently approved as monotherapy and in combination regimens for appropriate patients with metastatic or unresectable, recurrent HNSCC in the U.S., Europe, China, Japan and other countries around the world. For more information, please see the “Selected KEYTRUDA

KEYTRUDA目前已在美国、欧洲、中国、日本及世界其他国家和地区获批，作为单药治疗或联合治疗方案，用于合适的转移性或不可切除、复发性头颈部鳞状细胞癌（HNSCC）患者。欲了解更多信息，请参阅“精选KEYTRUDA”

(pembrolizumab) Indications in the U.S.” section below.

（派姆单抗）美国适应症”部分如下。

Study design and additional data from KEYNOTE-689

KEYNOTE-689的研究设计与额外数据

KEYNOTE-689 is a randomized, active-controlled, open-label Phase 3 trial (ClinicalTrials.gov,

KEYNOTE-689是一项随机、活性对照、开放标签的3期试验（ClinicalTrials.gov，

NCT03765918

NCT03765918

) evaluating KEYTRUDA as neoadjuvant treatment and KEYTRUDA in combination with standard of care radiotherapy (with or without cisplatin) as adjuvant treatment in treatment-naïve patients with newly diagnosed, stage III or IVA resectable, locally advanced head and neck squamous cell carcinoma (LA-HNSCC).

）评估KEYTRUDA作为新辅助治疗，以及KEYTRUDA联合标准护理放疗（含或不含顺铂）作为辅助治疗，用于初治、新诊断的III期或IVA期可切除的局部晚期头颈部鳞状细胞癌（LA-HNSCC）患者。

Efficacy outcomes are classified by programmed cell death ligand 1 (PD-L1) combined positive score (CPS) status. The primary endpoint is EFS, which is defined as the time from randomization to the first occurrence of radiographic disease progression; local or distant progression or recurrence; or death due to any cause.

疗效结果按程序性细胞死亡配体1（PD-L1）联合阳性评分（CPS）状态分类。主要终点是EFS，定义为从随机化到首次出现影像学疾病进展、局部或远处进展或复发、或任何原因导致死亡的时间。

The secondary endpoints include OS, mPR, pathological complete response and safety. The study enrolled 714 patients who were randomized 1:1 to receive:.

次要终点包括总生存期（OS）、主要病理缓解（mPR）、病理完全缓解和安全性。该研究招募了714名患者，他们被随机分配（1:1）接受：

KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W] for two cycles) as neoadjuvant therapy prior to surgery, followed by either KEYTRUDA (200 mg IV Q3W for 15 cycles) plus standard of care radiotherapy with cisplatin (100 mg/m

KEYTRUDA（200毫克静脉注射 [IV]，每三周 [Q3W] 一次，共两个周期）作为术前新辅助治疗，随后接受KEYTRUDA（200毫克静脉注射 [IV]，每三周 [Q3W] 一次，共15个周期）联合顺铂（100毫克/平方米）标准放疗。

IV Q3W for three cycles) as adjuvant therapy following surgery for high-risk patients or KEYTRUDA (200 mg IV Q3W for 15 cycles) plus standard of care radiotherapy without cisplatin as adjuvant therapy following surgery for low-risk patients; or

每3周一次静脉注射4个周期（高危患者手术后的辅助治疗）或KEYTRUDA（200毫克每3周一次静脉注射15个周期）加标准护理放疗但不含顺铂（低危患者手术后的辅助治疗）；或

No neoadjuvant therapy prior to surgery, followed by adjuvant standard of care radiotherapy with cisplatin (100 mg/m

手术前未接受新辅助治疗，术后接受顺铂（100 mg/m²）标准辅助放疗。

IV Q3W for three cycles) as adjuvant therapy following surgery for high-risk patients or standard of care radiotherapy without cisplatin as adjuvant therapy following surgery for low-risk patients.

每3周一次静脉注射，共三个周期，作为高危患者手术后的辅助治疗；或对于低危患者，采用不含顺铂的标准护理放疗作为手术后的辅助治疗。

The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 44.6% of patients receiving KEYTRUDA plus standard of care radiotherapy versus 42.9% of patients receiving standard of care radiotherapy alone.

KEYTRUDA的安全性特征与之前研究报告中观察到的一致。接受KEYTRUDA联合标准护理放疗的患者中有44.6%发生了≥3级治疗相关不良事件（TRAEs），而单独接受标准护理放疗的患者中有42.9%发生了此类事件。

TRAEs led to death in 1.1% of patients receiving the KEYTRUDA regimen (n=4) and 0.3% of patients receiving standard of care radiotherapy (n=1). No new safety concerns were identified. Immune-mediated adverse events (AEs) of any grade occurred in 43.2% of patients receiving the KEYTRUDA regimen, most commonly hypothyroidism (24.7%)..

在接受KEYTRUDA方案治疗的患者中，1.1%（n=4）因治疗相关不良事件（TRAEs）导致死亡，而接受标准护理放疗的患者中，0.3%（n=1）发生死亡。未发现新的安全性问题。在使用KEYTRUDA方案治疗的患者中，43.2%发生了任何级别的免疫介导不良事件（AEs），其中最常见的是甲状腺功能减退（24.7%）。

About head and neck cancer

关于头颈癌

Head and neck cancer describes a number of different tumors that develop in or around the throat, larynx, nose, sinuses and mouth. Most head and neck cancers are squamous cell carcinomas that begin in the flat, squamous cells that make up the thin surface layer of the structures in the head and neck.

头颈癌描述了在喉咙、喉头、鼻子、鼻窦和口腔内或周围发育的多种不同肿瘤。大多数头颈癌是鳞状细胞癌，起源于构成头颈部结构薄表面层的扁平鳞状细胞。

Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is cancer that has grown outside the original location, but has not yet spread to distant parts of the body. There are several factors that greatly increase the risk of developing head and neck cancer, including tobacco and alcohol use and human papillomavirus (HPV).

局部晚期头颈部鳞状细胞癌（LA-HNSCC）是指癌细胞已超出原发部位生长，但尚未扩散到身体远端。导致头颈癌风险显著增加的若干因素包括烟草和酒精使用以及人乳头瘤病毒（HPV）。

It is estimated there were more than 947,200 new cases of head and neck cancer diagnosed and over 482,400 deaths from the disease in 2022 globally. In the U.S., it is estimated there will be approximately 72,680 new cases of head and neck cancer diagnosed and more than 16,680 deaths from the disease in 2025..

据估计，2022年全球新增头颈癌病例超过947,200例，因该疾病导致的死亡人数超过482,400人。在美国，预计到2025年将有大约72,680例新诊断的头颈癌病例，并且因该疾病导致的死亡人数将超过16,680人。

About Merck’s early-stage cancer clinical program

关于默克早期癌症临床项目

Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is evaluating our portfolio of medicines and pipeline candidates in earlier disease states, with more than 30 ongoing registrational studies across multiple types of cancer..

在更早阶段发现癌症可能会给患者带来更大的长期生存机会。许多癌症在其病程的最早阶段被认为是最可治疗且潜在可治愈的。基于对KEYTRUDA在晚期癌症中作用的深刻理解，默克正在评估我们药物组合及其在更早期疾病状态中的候选药物，目前正在进行30多项涉及多种癌症类型的注册研究。

About KEYTRUDA

关于KEYTRUDA

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells..

KEYTRUDA是一种抗程序性死亡受体-1（PD-1）的疗法，通过增强人体免疫系统的能力来帮助检测和对抗肿瘤细胞。KEYTRUDA是一种人源化单克隆抗体，可阻断PD-1与其配体PD-L1和PD-L2之间的相互作用，从而激活T淋巴细胞，这可能对肿瘤细胞和健康细胞均产生影响。

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers..

默克公司拥有行业内最大的免疫肿瘤学临床研究项目。目前，有超过1600项试验正在研究KEYTRUDA在各种癌症和治疗环境中的应用。KEYTRUDA临床项目旨在了解KEYTRUDA在不同癌症中的作用，以及可能预测患者从KEYTRUDA治疗中获益可能性的因素，包括探索几种不同的生物标志物。