INDIANAPOLIS, Dec. 11, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced results from the Phase 3 EMBER-3 study of imlunestrant, an investigational, oral selective estrogen receptor degrader (SERD), in patients with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC), whose disease progressed on a prior aromatase inhibitor (AI), with or without a CDK4/6 inhibitor.

印第安纳波利斯，2024年12月11日/PRNewswire/--礼来公司（纽约证券交易所：LLY）今天宣布了imlunestrant的3期EMBER-3研究结果，imlunestrant是一种研究性口服选择性雌激素受体降解剂（SERD），用于雌激素受体阳性（ER+），人类表皮生长因子受体2阴性（HER2-）晚期乳腺癌（ABC）患者，其疾病在先前的芳香化酶抑制剂（AI）上进展，有或没有CDK4/6抑制剂。

Imlunestrant demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) as monotherapy in patients with an ESR1 mutation versus standard of care endocrine therapy (SOC ET), reducing the risk of disease progression or death by 38%. Imlunestrant in combination with Verzenio (abemaciclib; CDK4/6 inhibitor) reduced the risk of progression or death by 43% versus imlunestrant alone, in all patients..

与标准护理内分泌治疗（SOC ET）相比，Imlunestrant在ESR1突变患者的单药治疗中显示出无进展生存期（PFS）的统计学显着和临床意义的改善，将疾病进展或死亡的风险降低了38%。在所有患者中，与单独使用Imlunestrant相比，Imlunestrant联合Verzenio（abemaciclib；CDK4/6抑制剂）可将进展或死亡风险降低43%。。

These results were published in The New England Journal of Medicine and will be shared in a late-breaking oral presentation at the San Antonio Breast Cancer Symposium (SABCS) today, Wednesday, December 11 at 9:15 AM CT/10:15 AM ET. These data are being submitted to regulatory health authorities globally..

这些结果发表在《新英格兰医学杂志》上，并将于今天，12月11日星期三上午9:15/东部时间上午10:15在圣安东尼奥乳腺癌研讨会（SABCS）上发表最新的口头报告。这些数据正在提交给全球卫生监管机构。。

'The median progression free survival observed in EMBER-3 is among the most compelling we've seen in CDK4/6 pre-treated ER+, HER2- advanced breast cancer patients and indicates a potential shift in the therapy options we provide for these patients, which are currently very limited,' said Komal Jhaveri, M.D., section head, endocrine therapy research and clinical director, early drug development at Memorial Sloan Kettering Cancer Center, and one of the study's principal investigators.

“在EMBER-3中观察到的中位无进展生存期是我们在CDK4/6预处理的ER+，HER2晚期乳腺癌患者中看到的最令人信服的，这表明我们为这些患者提供的治疗选择可能发生变化，目前非常有限，”纪念斯隆·凯特琳癌症中心内分泌治疗研究科科马尔·贾弗里（KomalJhaveri）医学博士、早期药物开发临床主任和该研究的主要研究人员之一说。

'The benefit and safety profile of the imlunestrant and abemaciclib combination signal a potential new all-oral option for patients.'.

“imlunestrant和abemaciclib联合用药的益处和安全性标志着患者潜在的新的全口服选择。”。

In the EMBER-3 study, patients were randomized 1:1:1 to receive imlunestrant alone, SOC ET, or the imlunestrant-abemaciclib combination. Randomization was stratified by prior CDK4/6 inhibitor use, the presence of visceral metastases and geographic region. Patients enrolled as first line (1L) treatment for ABC (32%), following disease recurrence on or within 12 months of completing adjuvant AI, with or without CDK4/6 inhibitor for early breast cancer (EBC), or as second line (2L) treatment for ABC (64%), following progression on AI, with or without CDK4/6 inhibitor as initial therapy for ABC.

在EMBER-3研究中，患者以1:1:1的比例随机接受单独的imlunestrant，SOC ET或imlunestrant abemaciclib组合。通过先前使用CDK4/6抑制剂，内脏转移的存在和地理区域对随机化进行分层。患者入选为ABC的一线（1L）治疗（32%），在完成辅助AI后12个月内或12个月内疾病复发，有或没有CDK4/6抑制剂治疗早期乳腺癌（EBC），或作为二线（2L）治疗ABC（64%），在AI进展后，有或没有CDK4/6抑制剂作为ABC的初始治疗。

Primary endpoints were investigator-assessed PFS of imlunestrant versus SOC ET therapy in patients with ESR1 mutations, imlunestrant versus SOC ET in all patients, and imlunestrant-abemaciclib versus imlunestrant in all patients..

主要终点是研究者评估的ESR1突变患者的imlunestrant与SOC ET治疗的PFS，所有患者的imlunestrant与SOC ET，以及所有患者的imlunestrant abemaciclib与imlunestrant的PFS。。

Imlunestrant significantly improved PFS versus SOC ET in patients with an ESR1 mutation. In patients with an ESR1 mutation, median PFS was 5.5 months with imlunestrant versus 3.8 months with SOC ET [HR=0.62 (95% CI 0.46-0.82); p-value<0.001]. The overall response rate (ORR) with imlunestrant was 14% compared to 8% with SOC ET in patients with an ESR1 mutation.

与ESR1突变患者相比，Imlunestrant显着改善了PFS与SOC ET。在ESR1突变患者中，imlunestant的中位PFS为5.5个月，SOC ET为3.8个月[HR=0.62（95%CI 0.46-0.82）；p值<0.001]。在ESR1突变患者中，imlunestrant的总有效率（ORR）为14%，而SOC ET的总有效率（ORR）为8%。

In all patients, the median PFS was 5.6 months with imlunestrant versus 5.5 months with SOC ET [HR=0.87 (95% CI 0.72-1.04); p-value 0.12] and did not reach statistical significance..

在所有患者中，imlunestant的中位PFS为5.6个月，SOC ET为5.5个月[HR=0.87（95%CI 0.72-1.04）；p值0.12]，无统计学意义。。

Consistent with preclinical data demonstrating central nervous system (CNS) penetrance and CNS-activity of imlunestrant, CNS progression rates from a post-hoc analysis were lower with imlunestrant in all patients (HR=0.47; 95% CI, 0.16-1.38), as well as patients with an ESR1 mutation (HR=0.18; 95% CI, 0.04-0.90), however, these analyses are limited by low event numbers and lack of mandated serial asymptomatic CNS imaging in all patients..

与证明imlunestrant的中枢神经系统（CNS）外显率和CNS活性的临床前数据一致，所有患者（HR=0.47；95%CI，0.16-1.38）以及ESR1突变患者（HR=0.18；95%CI，0.04-0.90）的事后分析中，imlunestrant的CNS进展率均较低，然而，这些分析受到事件数量少和所有患者缺乏强制性连续无症状CNS成像的限制。。

Imlunestrant in combination with abemaciclib versus imlunestrant alone

Imlunestrant联合abemaciclib与单用Imlunestrant的比较

Imlunestrant-abemaciclib significantly improved PFS compared to imlunestrant in all patients, regardless of ESR1 mutation status, with median PFS of 9.4 months for imlunestrant-abemaciclib versus 5.5 months for imlunestrant alone [HR=0.57 (95% CI 0.44-0.73); p-value <0.001]. The PFS benefit of the combination was consistent across subgroups, regardless of ESR1 mutation, or PI3K pathway mutation status, and including in patients who had previously received CDK4/6 inhibitor treatment.

在所有患者中，无论ESR1突变状态如何，与Imlunestrant相比，Imlunestrant abemaciclib均显着改善了PFS，Imlunestrant abemaciclib的中位PFS为9.4个月，而单独使用Imlunestrant的中位PFS为5.5个月[HR=0.57（95%CI 0.44-0.73）；p值<0.001]。无论ESR1突变或PI3K途径突变状态如何，包括先前接受过CDK4/6抑制剂治疗的患者，该组合的PFS益处在各亚组中都是一致的。

In all patients, the ORR with imlunestrant-abemaciclib was 27% compared to 12% with imlunestrant alone..

在所有患者中，imlunestrant abemaciclib的ORR为27%，而单独使用imlunestrant的ORR为12%。。

Safety in the imlunestrant-abemaciclib arm was consistent with the known safety profile of fulvestrant in combination with abemaciclib, with mostly low-grade adverse events including diarrhea (86%), nausea (49%), neutropenia (48%) and anemia (44%), and had a low discontinuation rate (6.3%).1,2

imlunestrant abemaciclib组的安全性与氟维司群联合abemaciclib的已知安全性一致，主要是低度不良事件，包括腹泻（86%），恶心（49%），中性粒细胞减少（48%）和贫血（44%），停药率低（6.3%）。1,2

Overall survival (OS) results for EMBER-3 were immature at the time of analysis. The trial will continue to assess OS as a secondary endpoint.

在进行分析时，EMBER-3 的总生存期（OS）结果尚不成熟。该试验将继续评估作为次要终点的 OS。

'EMBER-3 is the first Phase 3 trial to show benefit of combining an oral SERD with a CDK4/6 inhibitor for a patient population where an all-oral regimen would represent a meaningful advance,' said David Hyman, M.D., Chief Medical Officer, Lilly. 'We're highly encouraged by these data for both imlunestrant as monotherapy and in combination with Verzenio, as well as the safety and tolerability profile, which demonstrate the potential for imlunestrant to be a meaningful new oral endocrine therapy option for patients.

礼来公司首席医疗官大卫·海曼（DavidHyman）医学博士说：“EMBER-3是第一个显示口服SERD与CDK4/6抑制剂联合使用对患者群体有益的3期临床试验，全口服方案将代表一个有意义的进步。”我们对imlunestrant作为单一疗法和与Verzenio联合使用的这些数据以及安全性和耐受性概况感到鼓舞，这表明imlunestrant有可能成为患者有意义的新型口服内分泌治疗选择。

We look forward to sharing these results with the oncology community and completing regulatory submissions to global health authorities.'.

我们期待着与肿瘤学界分享这些结果，并完成向全球卫生当局提交的监管报告。”。

An estimated 70 to 80% of hormone receptor positive breast cancers are ER+ and after progression on initial endocrine therapy, are predominantly treated with fulvestrant, which is administered by intramuscular injection in a doctor's office.3,4 According to patient-reported outcomes data from EMBER-3, 72% of patients receiving fulvestrant in the standard ET group reported injection site pain, swelling, or redness. Imlunestrant is an orally administered, brain penetrant, pure ER antagonist that delivers continuous ER target inhibition..

据估计，70%至80%的激素受体阳性乳腺癌是ER+，并且在初始内分泌治疗进展后，主要使用氟维司群治疗，氟维司群通过在医生办公室肌肉注射给药[3,4]。根据患者报告的结果来自EMBE-3的数据，标准ET组中72%接受氟维司群治疗的患者报告注射部位疼痛，肿胀或发红。Imlunestrant是一种口服给药的脑渗透性纯ER拮抗剂，可提供持续的ER靶标抑制作用。。

Imlunestrant is also being investigated in the adjuvant setting in people with ER+, HER2- early breast cancer (EBC) with an increased risk of recurrence. This Phase 3 trial, EMBER-4, is expected to enroll 6,000 EBC patients worldwide.

Imlunestrant也正在ER+，HER2早期乳腺癌（EBC）患者的辅助治疗中进行研究，复发风险增加。这项3期临床试验EMBE-4预计将在全球招募6000名EBC患者。

About EMBER-3 EMBER-3 is a Phase 3, randomized, open-label study of imlunestrant, investigator's choice of endocrine therapy, and imlunestrant in combination with abemaciclib in patients with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer whose disease has recurred or progressed during or following an aromatase inhibitor (AI) therapy with or without a CDK 4/6 inhibitor.

关于EMBER-3 EMBE-3是一项针对雌激素受体阳性（ER+），人表皮生长因子受体2阴性（HER2-）患者的imlunestrant，研究者选择内分泌治疗和imlunestrant联合abemaciclib的3期随机开放标签研究。局部晚期或转移性乳腺癌，其疾病在有或没有CDK 4/6抑制剂的芳香化酶抑制剂（AI）治疗期间或之后复发或进展。

The trial enrolled 874 adult patients, 32% of which enrolled from the adjuvant setting into first-line treatment of ABC and 64% as second line treatment following progression on initial therapy for ABC. Enrolled trial participants were randomized between imlunestrant, investigator's choice of fulvestrant or exemestane, or imlunestrant plus abemaciclib.

该试验招募了874名成年患者，其中32%从辅助治疗进入ABC的一线治疗，64%作为ABC初始治疗进展后的二线治疗。入选的试验参与者被随机分配到imlunestrant，研究者选择氟维司群或依西美坦，或imlunestrant加abemaciclib。

About Metastatic/Advanced Breast CancerMetastatic/advanced breast cancer (ABC) is a cancer that has spread from the breast tissue to other parts of the body. Locally advanced breast cancer means the cancer has grown outside the organ where it started but has not yet spread to other parts of the body.1 Of all high risk early-stage breast cancer cases diagnosed in the U.S., approximately 30% will become metastatic5 and an estimated 6-10% of all new breast cancer cases are initially diagnosed as being metastatic.6 Survival is lower among women with a more advanced stage of disease at diagnosis: five-year relative survival is 99% for localized disease, 86% for regional/locally advanced disease, and 30% for metastatic/advanced disease.7 Other factors, such as tumor size, also impact five-year survival estimates.7.

关于转移性/晚期乳腺癌转移性/晚期乳腺癌（ABC）是一种从乳腺组织扩散到身体其他部位的癌症。局部晚期乳腺癌意味着癌症已经在其开始的器官之外生长，但尚未扩散到身体的其他部位。在美国诊断出的所有高风险早期乳腺癌病例中，大约30%将成为转移性乳腺癌，估计所有新发乳腺癌病例中有6-10%最初被诊断为转移性乳腺癌。6诊断为疾病晚期的女性的生存率较低：局部疾病的五年相对生存率为99%，区域/局部晚期疾病的五年相对生存率为86%，转移/晚期疾病的五年相对生存率为30%。7其他因素，如肿瘤大小，也会影响五年生存率的估计值。

About Breast CancerBreast cancer is the second most commonly diagnosed cancer worldwide (following lung cancer), according to GLOBOCAN. The estimated 2.3 million new cases indicate that close to 1 in every 4 cancers diagnosed in 2022 is breast cancer. With approximately 666,000 deaths in 2022, breast cancer is the fourth-leading cause of cancer death worldwide.8 In the U.S., it is estimated that there will be more than 310,000 new cases of breast cancer diagnosed in 2024.

关于乳腺癌根据GLOBOCAN的数据，乳腺癌是全球第二大最常被诊断的癌症（仅次于肺癌）。据估计，230万新病例表明，2022年诊断出的每4种癌症中就有近1种是乳腺癌。2022年约有666000人死亡，乳腺癌是全球第四大癌症死亡原因。8在美国，估计2024年将有超过310000例新诊断的乳腺癌病例。

Breast cancer is the second leading cause of cancer death in women in the U.S.9.

乳腺癌是美国妇女癌症死亡的第二大原因9。

About Imlunestrant Imlunestrant is a brain-penetrant, oral selective estrogen receptor degrader (SERD), that delivers continuous ER inhibition, including in ESR1-mutant cancers. The estrogen receptor (ER) is the key therapeutic target for patients with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer.

关于Imlunestrant Imlunestrant是一种脑渗透剂，口服选择性雌激素受体降解剂（SERD），可提供持续的ER抑制作用，包括在ESR1突变型癌症中。雌激素受体（ER）是雌激素受体阳性（ER+），人表皮生长因子受体2阴性（HER2-）乳腺癌患者的关键治疗靶点。

Novel degraders of ER may overcome endocrine therapy resistance while providing consistent oral pharmacology and convenience of administration. Imlunestrant is currently being studied as a treatment for advanced breast cancer and as an adjuvant treatment in early breast cancer, including: NCT04975308, NCT05514054, NCT04188548, NCT05307705..

ER的新型降解剂可以克服内分泌治疗耐药性，同时提供一致的口服药理学和给药便利性。目前正在研究Imlunestrant作为晚期乳腺癌的治疗方法和早期乳腺癌的辅助治疗方法，包括：NCT04975308，NCT05514054，NCT04188548，NCT05307705。。

About Verzenio® (abemaciclib)Verzenio® (abemaciclib) is approved to treat people with certain HR+, HER2- breast cancers in the adjuvant and advanced or metastatic setting. Verzenio is the first CDK4/6 inhibitor approved to treat node-positive, high risk early breast cancer (EBC) patients.10 For HR+, HER2- breast cancer, The National Comprehensive Cancer Network® (NCCN®) recommends consideration of two years of abemaciclib (Verzenio) added to endocrine therapy as a Category 1 treatment option in the adjuvant setting.11 NCCN® also includes Verzenio plus endocrine therapy as a preferred treatment option for HR+, HER2- metastatic breast cancer.11.

关于Verzenio®（abemaciclib）Verzenio®（abemaciclib）被批准用于治疗某些HR+，HER2乳腺癌患者的辅助治疗和晚期或转移治疗。Verzenio是第一个被批准用于治疗淋巴结阳性，高危早期乳腺癌（EBC）患者的CDK4/6抑制剂.10对于HR+，HER2-乳腺癌，国家综合癌症网络®（NCCN®）建议考虑两年的abemaciclib（Verzenio）作为辅助治疗中的1类治疗选择添加到内分泌治疗中.11 NCCN®还包括Verzenio加内分泌治疗作为HR+，HER2-转移性乳腺癌的首选治疗选择。

The collective results of Lilly's clinical development program continue to differentiate Verzenio as a CDK4/6 inhibitor. In high risk EBC, Verzenio has shown a persistent and deepening benefit beyond the two-year treatment period in the monarchE trial, an adjuvant study designed specifically to investigate a CDK4/6 inhibitor in a node-positive, high risk EBC population.12 In metastatic breast cancer, Verzenio has demonstrated statistically significant OS in the Phase 3 MONARCH 2 study.13 Verzenio has shown a consistent and generally manageable safety profile across clinical trials..

礼来公司临床开发计划的集体结果继续将Verzenio区分为CDK4/6抑制剂。在高风险EBC中，Verzenio在MONARCE试验中显示出持续且深入的益处，该试验是一项辅助研究，专门用于研究淋巴结阳性，高风险EBC人群中的CDK4/6抑制剂.12在转移性乳腺癌中，Verzenio在3期MONARCH 2研究中显示出统计学上显着的OS.13 Verzenio在临床试验中显示出一致且通常可管理的安全性。。

Verzenio is an oral tablet taken twice daily and available in strengths of 50 mg, 100 mg, 150 mg, and 200 mg. Discovered and developed by Lilly researchers, Verzenio was first approved in 2017 and is currently authorized for use in more than 90 counties around the world. For full details on indicated uses of Verzenio in HR+, HER2- breast cancer, please see full Prescribing Information, available at www.Verzenio.com..

Verzenio是一种口服片剂，每天服用两次，剂量分别为50 mg、100 mg、150 mg和200 mg。由礼来研究人员发现和开发的Verzenio于2017年首次获得批准，目前已授权在全球90多个国家使用。有关Verzenio在HR+，HER2-乳腺癌中指定用途的完整详细信息，请参阅www.Verzenio.com上提供的完整处方信息。。

About Lilly

关于礼来

Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases.

礼来是一家将科学转化为治疗的医药公司，旨在让世界各地的人们生活得更好。近150年来，我们一直在开创改变生活的发现，今天，我们的药物帮助了全球数以千万计的人。利用生物技术、化学和遗传医学的力量，我们的科学家正在迫切推进新发现，以解决世界上一些最重大的健康挑战：重新定义糖尿病护理；治疗肥胖并减少其最具破坏性的长期影响；推进与阿尔茨海默病的斗争；为一些最令人衰弱的免疫系统疾病提供解决方案；并将最难治疗的癌症转化为可控制的疾病。