MEN-1611

与 SOC 内分泌 疗法相比，艾拉司群的无进展生存期（ PFS ）更 长，中位数可达 8.6 个月，与既往使用 CDK4/6 抑制 剂治疗的持续时间呈正相关 艾拉司群的副作用易于控制，并与既往 报告的结果保持一致 结果表明，对于 CDK4/6i 进展后的 ER+ 、 HER2- 晚期或 转移性乳腺癌，艾拉司群或将作为一种单药疗法内分泌测序选项成为一项新护理标准 意大利佛罗伦萨 2022年12月2日 /美通社/ -- 意大利私营制药及诊断公司美纳里尼集团（Menarini Group，以下简称为"美纳里尼"）和美纳里尼集团全资子公司Stemline Therapeutics（以下简称为"Stemline"），将在12月6日至10日举行的圣安东尼奥乳腺癌研讨会（SABCS）上公布试验性口服SERD药物艾拉司群（Elacestrant）3期EMERALD研究（NCT03778931）的更多数据。 EMERALD是一项3期注册试验，证明了在ER+、HER2-晚期或转移性乳腺癌中使用CDK4/6抑制剂（CDK4/6i）的进展后，在所有患者和携带ESR1突变（ESR1-mut）的患者中，艾拉司群相比SOC内分泌单药疗法（氟维司群、来曲唑、阿那曲唑、依西美坦）具有统计学上的显著无进展生存期（PFS），符合两个主要终点。 根据既往使用CDK4/6i的持续时间，对EMERALD试验中PFS结果的事后分析表明，无论是在总患者群还是ESR1突变患者中，有临床意义的结果均支持艾拉司群单药治疗。转移性患者既往CDK4/6i持续时间的延长与艾拉司群治疗的PFS延长呈正相关，但与SOC无关。 对于在EMERALD随机化之前接触CDK4/6i超过12个月的患者，艾拉司群实现了以下效果： 在总患者群中，艾拉司群的mPFS为3.8个月，SOC为1.9个月，进展或死亡风险降低39%（HR=0.61 95% CI：0.45-0.83） 在ESR1-mut患者群中，艾拉司群的mPFS为8.6个月，SOC为1.9个月，进展或死亡风险降低59%（HR=0.41 95% CI：0.26-0.63） 对于在EMERALD随机化之前接触CDK4/6i超过18个月的患者，艾拉司群实现了以下效果： 在总患者群中，艾拉司群的mPFS为5.5个月，SOC为3.3个月，进展或死亡风险降低30%（HR=0.70 95% CI：0.48-1.02） 在ESR1-mut患者群中，艾拉司群的mPFS为8.6个月，SOC为2.1个月，进展或死亡风险降低53%（HR=0.47 CI：0.20-0.79） 。 更新后的安全数据与先前报告的结果一致。包括恶心在内的大多数不良事件（AE）均为1级和2级，只有3.4%和0.9%的患者分别因艾拉司群和SOC的不良事件而中止了试验治疗。接受止吐药物的患者比例较低；分别是艾拉司群为8.0%，氟维司群为3.7%，AI为10.3%。尚未观察到血液学安全信号，两个治疗组中患者均未表现窦性心搏徐缓。 得克萨斯大学圣安东尼奥健康科学中心（UT Health San Antonio）、得克萨斯大学安德森癌症中心（UT MD Anderson Cancer Center）医学博士、科学博士、乳腺癌肿瘤学家兼医学教授Virginia Kaklamani评论道："这些结果表明，根据既往CDK4/6抑制剂治疗的持续时间，艾拉司群作为单一药物使用时，可提供长达8.6个月的mPFS，具有可控的安全性和口服片剂便捷性。结果表明，对于CDK4/6i进展后的ER+、HER2-晚期乳腺癌，在转入联合疗法之前，艾拉司群或将作为一种单药疗法内分泌测序选择成为一项新护理标准。" 美纳里尼集团首席执行官Elcin Barker Ergun表示："这些结果进一步凸显了艾拉司群改变ER+、HER2-晚期或转移性乳腺癌治疗模式的潜力。艾拉司群正在接受美国食品药品监督管理局（FDA）的优先审查，目标审查到期日（PDUFA Date）为2023年2月17日。" 以下是美纳里尼集团在SABCS上发表重要演讲的完整列表。 第一作者姓名 摘要 编号和标题 报告详情 V. Kaklamani GS3-01. 在 ER+ 、 HER2- 转移性乳腺癌患者中， EMERALD 3 期艾拉司群 试验相比的标准护理内分泌治疗：既往 CDK4/6i 在 转移环境下持续时间的最新结果 2022 年 12 月 8 日 中部 时间上午 8:30-8:45 口述 报告 一般性会 议 3 大 厅 3 H. Rugo OT2-01-03. ELEVATE ： 1b/2 期开放 标签综合研究评估艾拉司群在转移性乳腺癌（ mBC ）女性和男性患者中的各种 联合用药 2022 年 12 月 7 日 中部 时间下午 5:00-6:30 正在 进行的试验图片式会议 2 大 厅 1 M. Piccart PD18-05 。 MEN1611 是一种 PI3K 抑制 剂，联合曲妥珠单抗（ T ） ± 氟 维司群（ F ）治 疗 HER2+/PIK3CA 突 变（ mut ）晚期或 转移性（ a/m ）乳腺癌（ BC ）：正在 进行的 1b 期研究（ B-PRECISE-01 ）更新的安全性和 疗效结果 2022 年 12 月 9 日 中部 时间上午 7:00-8:15 聚焦海 报讨论 18 群星夜 间宴会厅 —— 大 厅 3 和 4 美纳里尼集团于2020年7月从实施并成功完成EMERALD研究的Radius Health, Inc获得了艾拉司群的全球授权。美纳里尼集团现在全面负责艾拉司群的全球注册、商业化和进一步开发活动。 关于艾拉司群（ RAD1901 ）和 EMERALD 3 期研究 艾拉司群是一种试验性选择性雌激素受体降解剂（SERD）。2018年，艾拉司群获得美国食品药品监督管理局授予的快速通道资格。在EMERALD之前完成的临床前研究表明，该化合物具有作为单一药剂或与其他疗法联合使用以治疗乳腺癌的可能性。EMERALD 3期试验是一项随机、开放标签、主动对照研究，评估艾拉司群能否作为ER+\/HER2-晚期\/转移性乳腺癌患者的二线或三线单药疗法。该研究共入组了478名患者，他们曾接受过一种或两种内分泌治疗，包括CDK 4\/6抑制剂。研究中的患者随机接受艾拉司群或研究人员所选择的经批准激素制剂。该研究的主要终点是总患者群和雌激素受体1基因（ESR1）突变患者的无进展生存期（PFS）。次要终点包括评估总生存期（OS）、客观缓解率（ORR）以及缓解持续时间（DOR）和安全性。 关于美 纳里尼集团 美纳里尼集团（Menarini Group）是一家领先的国际制药和诊断公司，拥有1.7万多名员工，营业额超过40亿美元。美纳里尼专注于心脏病学、肿瘤学、肺病学、胃肠病学、传染病学、糖尿病学、炎症和镇痛学等需求高度未得到满足的治疗领域。美纳里尼拥有18处生产基地和9所研发中心，产品遍布全球140个国家和地区。如需了解更多信息，请访问www.menarini.com。 关于 Stemline Therapeutics是美纳里尼集团的全资子公司，是一家专注于新型肿瘤疗法开发和商业化的商业阶段生物制药公司。Stemline为美国和欧洲的母细胞性浆细胞样树突细胞肿瘤（BPDCN）患者提供针对CD123的新型靶向治疗，该疗法同时也在针对各种其他适应症的其他临床试验中作为单药疗法和与其他制剂一起进行评估。Stemline在一系列固体和血液癌症的不同开发阶段拥有广泛的小分子和生物制剂临床管道。 关于 Radius Radius是一家全球性生物制药公司，专注于解决骨健康和肿瘤领域未得到满足的医疗需求。Radius的领先产品TYMLOS®（阿巴洛肽）注射液已获得美国食品药品监督管理局批准，可用于治疗患有骨质疏松症且具有高骨折风险的绝经后女性。Radius临床管线包括包括潜在用于治疗男性骨质疏松症的试验性阿巴帕肽（Abaloparatide）注射液和潜在用于治疗激素受体阳性乳腺癌的研究药物艾拉司群（RAD1901），该药物已授权给美纳里尼集团。

FLORENCE, Italy--( BUSINESS WIRE )--The Menarini Group (“Menarini”), a privately held Italian pharmaceutical and diagnostics company, and Stemline Therapeutics (“Stemline”), a wholly-owned subsidiary of the Menarini Group, will present additional data from the Phase 3 EMERALD study (NCT03778931) of elacestrant, an investigational oral SERD, during the upcoming San Antonio Breast Cancer Symposium (SABCS) being held from December 6-10. EMERALD is a Phase 3 registrational trial that demonstrated statistically significant progression-free survival (PFS) with elacestrant vs SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane), meeting both primary endpoints in all patients and in those patients harbouring ESR1 mutations (ESR1-mut), following progression on prior CDK4/6 inhibitors (CDK4/6i) in ER+, HER2- advanced or metastatic breast cancer. A post-hoc analysis of the PFS results in the EMERALD trial based on the duration of prior CDK4/6i usage shows clinically meaningful results which favor monotherapy elacestrant, both in the total patient population as well as in patients with ESR1-mut. Increased duration of prior CDK4/6i in metastatic patients was positively associated with longer PFS on elacestrant but not with SOC. For those who were exposed to CDK4/6i ≥12 months prior to randomization on EMERALD, elacestrant achieved: In the all-patient population, a mPFS of 3.8 months on elacestrant vs 1.9 months on SOC, a 39% reduction in the risk of progression or death (HR=0.61 95% CI: 0.45-0.83) In the ESR1-mut population, a mPFS of 8.6 months on elacestrant vs 1.9 months on SOC, a 59% reduction in the risk of progression or death (HR=0.41 95% CI: 0.26-0.63) For those who were exposed with CDK4/6i ≥18 months prior to randomization on EMERALD, elacestrant achieved: In the all-patient population, a mPFS of 5.5 months on elacestrant vs 3.3 months with SOC, a 30% reduction in the risk of progression or death (HR=0.70 95% CI: 0.48-1.02) In the ESR1-mut population, a mPFS of 8.6 months on elacestrant vs 2.1 months on SOC, a 53% reduction in the risk of progression or death (HR=0.47 CI: 0.20-0.79) . Updated safety data were consistent with previously reported results. Most of the adverse events (AEs), including nausea, were grade 1 and 2, and only 3.4% and 0.9% of the patients discontinued trial therapy because of an AE on elacestrant and SOC, respectively. A low percentage of patients received an antiemetic; 8.0% on elacestrant, 3.7% on fulvestrant, and 10.3% on AI, respectively. No hematological safety signal was observed and none of the patients in either of the two treatment arms had sinus bradycardia. Virginia Kaklamani, MD, DSc, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center, commented, “These results show that when used as a single agent, elacestrant provided mPFS up to 8.6 months, based on the duration of previous CDK4/6 inhibitor therapy, with a manageable safety profile and the convenience of an oral tablet. This suggests elacestrant may have the potential to become a new standard of care as a monotherapy endocrine sequencing option in ER+, HER2- advanced breast cancer after progression on CDK4/6i, before moving to combination therapies.” “These results further highlight elacestrant’s potential to change the treatment paradigm of ER+, HER2- advanced or metastatic breast cancer. Elacestrant is under Priority Review with the U.S. Food and Drug Administration (FDA) with a target PDUFA date of February 17, 2023,” commented Elcin Barker Ergun, Chief Executive Officer of the Menarini Group. A complete list of key Menarini Group presentations at SABCS is below. Lead Author Name Abstract Number and Title Presentation Details V. Kaklamani GS3-01. EMERALD Phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+, HER2- metastatic breast cancer: Updated results by duration of prior CDK4/6i in metastatic setting December 8, 2022 8:30-8:45 AM CT Oral Presentation General Session 3 Hall 3 H. Rugo OT2-01-03. ELEVATE: A Phase 1b/2, open-label, umbrella study evaluating elacestrant in various combinations in women and men with metastatic breast cancer (mBC) December 7, 2022 5:00-6:30 PM CT Ongoing Trials Poster Session 2 Hall 1 M. Piccart PD18-05. MEN1611, a PI3K Inhibitor, combined with trastuzumab (T) ± fulvestrant (F) for HER2+/PIK3CA mutant (mut) advanced or metastatic (a/m) breast cancer (BC): updated safety and efficacy results from the ongoing Phase 1b study (B-PRECISE-01) December 9, 2022 7:00-8:15 AM CT Spotlight Poster Discussion 18 Stars at Night Ballroom - Hall 3&4 The Menarini Group obtained global licensing rights for elacestrant in July 2020 from Radius Health, Inc., who conducted and successfully completed the EMERALD study. The Menarini Group is now fully responsible for global registration, commercialization, and further development activities for elacestrant. About Elacestrant (RAD1901) and the EMERALD Phase 3 Study Elacestrant is an investigational selective estrogen receptor degrader (SERD). In 2018, elacestrant received Fast Track designation from the FDA. Preclinical studies completed prior to EMERALD indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. The study enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK 4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator’s choice of an approved hormonal agent. The primary endpoints of the study were progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. Secondary endpoints included evaluation of overall survival (OS), objective response rate (ORR), and duration of response (DOR) and safety. About The Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini’s products are available in 140 countries worldwide. For further information, please visit www.menarini.com . About Stemline Stemline Therapeutics, a wholly owned subsidiary of The Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics. Stemline commercializes a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the United States and Europe which is also being evaluated as monotherapy and in combination with other agents, in additional clinical trials for a variety of other indications. Stemline has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers. About Radius Radius is a global biopharmaceutical company focused on addressing unmet medical needs in the areas of bone health and oncology. Radius’ lead product, TYMLOS® (abaloparatide) injection, was approved by the U.S. Food and Drug Administration for the treatment of postmenopausal women with osteoporosis at high risk for fracture. The Radius clinical pipeline includes investigational abaloparatide injection for potential use in the treatment of men with osteoporosis and the investigational drug, elacestrant (RAD1901), for potential use in the treatment of hormone-receptor positive breast cancer out-licensed to Menarini Group.