Positive high-level results from a planned interim analysis of the SERENA-6 Phase III trial showed that AstraZeneca’s camizestrant in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (palbociclib, ribociclib or abemaciclib) demonstrated a highly statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS).

计划中的SERENA-6 III期试验的中期分析得出了积极的高水平结果，结果显示阿斯利康的camizestrant与细胞周期蛋白依赖性激酶（CDK）4/6抑制剂（palbociclib、ribociclib或abemaciclib）联合使用，在无进展生存期（PFS）的主要终点上表现出高度统计学显著性和临床意义的改善。

The trial evaluated switching to the camizestrant combination versus continuing standard-of-care treatment with an aromatase inhibitor (AI) (anastrozole or letrozole) in combination with a CDK4/6 inhibitor in the 1st-line treatment of patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumours have an emergent ESR1 mutation..

该试验评估了在激素受体（HR）阳性、HER2阴性的晚期乳腺癌患者中，其肿瘤具有新发ESR1突变的情况下，转换为camizestrant联合治疗与继续使用芳香化酶抑制剂（AI）（阿那曲唑或来曲唑）联合CDK4/6抑制剂作为一线治疗的对比效果。

The key secondary endpoints of time to second disease progression (PFS2) and overall survival (OS) were immature at the time of this interim analysis. However, the camizestrant combination demonstrated a trend toward improvement in PFS2. The trial will continue as planned to further assess key secondary endpoints..

次要终点指标第二次疾病进展时间（PFS2）和总生存期（OS）在本次中期分析时数据尚不成熟。然而，camizestrant联合治疗组显示出PFS2改善的趋势。试验将继续按计划进行，以进一步评估关键的次要终点指标。

SERENA-6 is the first global, double-blind, registrational Phase III trial to use a circulating tumour DNA (ctDNA)-guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression. The novel trial design used ctDNA monitoring at the time of routine tumour scan visits to identify patients for early signs of endocrine resistance and the emergence of ESR1 mutations.

SERENA-6 是全球首个采用循环肿瘤 DNA (ctDNA) 引导方法的双盲注册性 III 期试验，用于检测内分泌抵抗的出现，并在疾病进展前指导治疗方案的转换。该新颖的试验设计在常规肿瘤扫描访视时通过 ctDNA 监测来识别患者是否出现内分泌抵抗的早期迹象以及 ESR1 突变的出现。

Following detection of an ESR1 mutation without disease progression, the endocrine therapy of patients was switched to camizestrant from ongoing treatment with an AI, while continuing combination with the same CDK4/6 inhibitor..

在检测到ESR1突变但疾病未进展的情况下，患者的内分泌治疗从正在进行的芳香酶抑制剂（AI）治疗转换为卡米泽斯特，同时继续与相同的CDK4/6抑制剂联合使用。

François-Clément Bidard, MD, PhD, Professor of Medical Oncology at Institut Curie & UVSQ/Université Paris-Saclay, France, and co-principal investigator for the trial, said: “Patients have an urgent need for new treatments that delay disease progression on 1st-line endocrine-based therapies. The results from SERENA-6 show that switching from an aromatase inhibitor to camizestrant in combination with any of the three CDK4/6 inhibitors after emergence of an ESR1 mutation delays progression of disease and extends the benefit of 1st-line treatment, representing an important step forward for patients, and a potential shift in clinical practice.”.

François-Clément Bidard，医学博士，法国居里研究所及UVSQ/巴黎萨克雷大学医学肿瘤学教授，同时也是该试验的联合首席研究员，他表示：“患者迫切需要能够延缓一线内分泌治疗疾病进展的新疗法。SERENA-6试验的结果表明，在出现ESR1突变后，将芳香化酶抑制剂替换为卡米泽斯特与三种CDK4/6抑制剂中的任何一种联用，可以延缓疾病进展并延长一线治疗的益处，这对患者而言是一个重要的进步，也可能带来临床实践的重大转变。”

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: 'These impressive results demonstrate the versatility of camizestrant in combination with all the widely approved CDK4/6 inhibitors to provide a well-tolerated new potential treatment option in the first-line setting for the one in three patients with HR-positive, HER2-negative advanced breast cancer whose tumours develop ESR1 mutations during treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor.

阿斯利康肿瘤血液学研发执行副总裁苏珊·加尔布雷思表示：“这些令人印象深刻的结果展示了卡米泽司坦与所有广泛获批的CDK4/6抑制剂联合使用的多功能性，为三分之一在接受芳香酶抑制剂与CDK4/6抑制剂联合治疗期间肿瘤出现ESR1突变的HR阳性、HER2阴性晚期乳腺癌患者，提供了一种在一线治疗中耐受性良好的潜在新治疗选择。”

This critical read-out moves us one step closer to realising the potential of camizestrant to become a new standard-of-care as we look to shift the treatment paradigm and establish this new endocrine therapy backbone in HR-positive breast cancer.”.

这一关键的读数使我们更接近实现camizestrant成为新护理标准的潜力，因为我们希望转变治疗模式，并在激素受体阳性乳腺癌中建立这种新的内分泌治疗支柱。

The safety profile of camizestrant in combination with palbociclib, ribociclib or abemaciclib in SERENA-6 was consistent with the known safety profile of each medicine. No new safety concerns were identified and discontinuations were very low and similar in both arms.

在SERENA-6试验中，卡米泽斯特与帕博西尼、瑞博西尼或阿贝西利联合使用的安全性特征与每种药物已知的安全性特征一致。未发现新的安全性问题，且两组的停药率均很低且相似。

Globally, approximately 200,000 patients with HR-positive breast cancer are treated with a medicine in the 1st-line setting; most frequently with endocrine therapies that target estrogen receptor (ER)-driven disease, which are often paired with CDK4/6 inhibitors.1-3 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.3.

全球范围内，大约有200,000名HR阳性的乳腺癌患者在一线治疗中接受药物治疗；最常见的是使用针对雌激素受体（ER）驱动疾病的内分泌疗法，这些疗法通常与CDK4/6抑制剂联合使用。然而，在许多晚期疾病患者中，对CDK4/6抑制剂和当前内分泌疗法的耐药性逐渐发展。

Mutations in the ESR1 gene are a key driver of endocrine resistance and are widely tested for in clinical practice.4,5 These mutations develop during treatment of the disease, becoming more prevalent as the disease progresses and are associated with poor outcomes.4,5 Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment without disease progression.1.

ESR1基因突变是内分泌抵抗的关键驱动因素，在临床实践中被广泛检测。这些突变在疾病治疗过程中出现，随着疾病进展变得更加普遍，并与不良预后相关。大约30%的内分泌敏感性HR阳性患者在一线治疗期间，在无疾病进展的情况下会出现ESR1突变。

Data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

数据将在即将召开的医学会议上公布，并与全球监管机构分享。

Notes

笔记

HR-positive breast cancer

HR阳性的乳腺癌

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.6 More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally.6 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.7.

乳腺癌是全球第二大常见癌症，也是导致癌症相关死亡的主要原因之一。2022年，超过两百万患者被诊断出患有乳腺癌，全球范围内超过665,000人死亡。虽然早期乳腺癌患者的存活率较高，但只有大约30%的转移性疾病患者预计在诊断后能活五年。

HR-positive breast cancer, characterised by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumours considered HR-positive and HER2-negative.7 ERs often drive the growth of HR-positive breast cancer cells.8

HR阳性乳腺癌，以雌激素或孕激素受体的表达为特征，或者两者都有，是最常见的乳腺癌亚型，其中70%的肿瘤被认为是HR阳性和HER2阴性。ERs常常驱动HR阳性乳腺癌细胞的生长。

Once resistance to the treatment of HR-positive breast cancer with CDK4/6 inhibitors and current endocrine therapies occurs, treatment options are limited and survival rates are low with 35% of patients anticipated to live beyond five years after diagnosis.3,7,9 The optimisation of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research..

一旦HR阳性乳腺癌对CDK4/6抑制剂和当前内分泌治疗产生耐药性，治疗选择将十分有限，生存率较低，预计仅有35%的患者在诊断后存活超过五年。优化内分泌治疗、克服耐药性以使患者继续从中受益，以及为那些不太可能受益的患者寻找新疗法，是乳腺癌研究的重点领域。

SERENA-6

SERENA-6

SERENA-6 is a Phase III, double-blind, randomised trial evaluating the efficacy and safety of camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib ) versus treatment with an AI (anastrozole or letrozole) in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) in patients with HR-positive, HER2-negative advanced breast cancer (patients with either locally advanced disease, or metastatic disease) whose tumours have an emergent ESR1 mutation..

SERENA-6是一项III期、双盲、随机试验，评估了camizestrant联合CDK4/6抑制剂（palbociclib、ribociclib或abemaciclib）与AI（anastrozole或letrozole）联合CDK4/6抑制剂（palbociclib、ribociclib或abemaciclib）在HR阳性、HER2阴性晚期乳腺癌患者中的疗效和安全性（包括局部晚期或转移性疾病患者），这些患者的肿瘤具有新出现的ESR1突变。

The global trial enrolled 315 adult patients with histologically confirmed HR-positive, HER2-negative advanced breast cancer, undergoing treatment with an AI in combination with a CDK4/6 inhibitor as 1st-line treatment. The primary endpoint of the SERENA-6 trial is PFS as assessed by investigator, with secondary endpoints including OS, and PFS2 by investigator assessment..

全球试验招募了315名组织学确认的HR阳性、HER2阴性晚期乳腺癌成年患者，这些患者接受一种芳香化酶抑制剂（AI）与CDK4/6抑制剂组合作为一线治疗。SERENA-6试验的主要终点是由研究者评估的无进展生存期（PFS），次要终点包括总生存期（OS）和研究者评估的第二次无进展生存期（PFS2）。

Camizestrant

卡米泽司坦

Camizestrant is an investigational, potent, next-generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist that is currently in Phase III trials for the treatment of HR-positive breast cancer.

Camizestrant 是一种研究中的高效下一代口服选择性雌激素受体降解剂 (SERD) 和完全 ER 拮抗剂，目前正处于治疗 HR 阳性乳腺癌的 III 期临床试验阶段。

AstraZeneca’s broad, robust and innovative clinical development programme, including the SERENA-6, SERENA-4, CAMBRIA-1 and CAMBRIA-2 trials, is evaluating the safety and efficacy of camizestrant when used as a monotherapy or in combination with other agents to address a number of areas of unmet need in this specific type of breast cancer..

阿斯利康广泛、强大且创新的临床开发计划，包括SERENA-6、SERENA-4、CAMBRIA-1和CAMBRIA-2试验，正在评估camizestrant作为单一疗法或与其他药物联合使用时的安全性和有效性，以解决这种特定类型乳腺癌中许多未满足需求的领域。

Camizestrant has demonstrated anti-cancer activity across a range of preclinical models, including those with ER-activating mutations. In the SERENA-2 Phase II trial, camizestrant demonstrated PFS benefit versus Faslodex (fulvestrant) irrespective of ESR1 mutation status or prior treatment with CDK4/6 inhibitors in patients with ER-positive locally advanced or metastatic breast cancer, previously treated with endocrine therapy.

Camizestrant 在一系列临床前模型中展示了抗癌活性，包括那些具有雌激素受体激活突变的模型。在 SERENA-2 II 期试验中，对于之前接受过内分泌治疗的雌激素受体阳性局部晚期或转移性乳腺癌患者，无论其 ESR1 突变状态或先前是否接受过 CDK4/6 抑制剂治疗，camizestrant 均显示出相对于 Faslodex（氟维司群）的无进展生存期（PFS）优势。

The SERENA-1 Phase I trial demonstrated that camizestrant is well tolerated and has a promising anti-tumour profile when administered alone or in combination with palbociclib, ribociclib and abemaciclib; three widely used CDK4/6 inhibitors. Combinations with other agents are ongoing in SERENA-1..

SERENA-1 一期试验表明，卡米泽斯特单用或与帕博西尼、瑞博西尼和阿贝西利三种广泛使用的CDK4/6抑制剂联合使用时，耐受性良好且具有良好的抗肿瘤特性。与其他药物的联合使用正在SERENA-1中进行。

AstraZeneca in breast cancer

阿斯利康在乳腺癌领域

Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death..

随着对乳腺癌生物学认识的不断加深，阿斯利康正在挑战并重新定义当前乳腺癌分类和治疗的临床模式，旨在为有需要的患者提供更有效的治疗方法，并怀揣着有朝一日消除乳腺癌作为死亡原因的宏伟目标。

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

阿斯利康拥有一个全面的已批准和有前景的在研化合物组合，这些化合物利用不同的作用机制来应对生物多样性乳腺癌肿瘤环境。

With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings..

通过Enhertu（trastuzumab deruxtecan），一种HER2导向的ADC，阿斯利康和第一三共旨在改善先前治疗过的HER2阳性、HER2低表达和HER2超低表达转移性乳腺癌的预后，并正在探索其在更早治疗线和新的乳腺癌环境中的潜力。

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP-2-directed ADC, Datroway (datopotamab deruxtecan) and next-generation oral SERD and potential new medicine camizestrant..

在HR阳性的乳腺癌领域，阿斯利康通过基础药物Faslodex和Zoladex（戈舍瑞林）持续改善治疗效果，并致力于通过首创的AKT抑制剂Truqap（capivasertib）、靶向TROP-2的ADC药物Datroway（datopotamab deruxtecan）、下一代口服SERD以及潜在新药camizestrant重新定义HR阳性领域的治疗格局。

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease.

PARP抑制剂Lynparza（奥拉帕尼）是一种靶向治疗选择，已在携带遗传性BRCA突变的早期和转移性乳腺癌患者中进行了研究。阿斯利康与MSD（美国和加拿大的默克公司）继续在这些环境中研究Lynparza，并探索其在更早期疾病中的潜力。

AstraZeneca is also exploring the efficacy and safety of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer..

阿斯利康还在研究PARP1的有效和选择性抑制剂saruparib与camizestrant联合使用在BRCA突变、HR阳性、HER2阴性的晚期乳腺癌中的疗效和安全性。

To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi (durvalumab).

为了给三阴性乳腺癌（一种侵袭性乳腺癌）患者带来亟需的治疗选择，阿斯利康正与第一三共合作，评估Datroway单药以及与免疫疗法Imfinzi（durvalumab）联合使用的潜力。

AstraZeneca in oncology

阿斯利康在肿瘤学领域

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

阿斯利康正引领一场肿瘤学革命，致力于为各种形式的癌症提供治愈方案，遵循科学精神深入了解癌症及其复杂性，发现、开发并交付改变生命的药物给患者。

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

公司的重点是一些最具挑战性的癌症。正是通过不懈的创新，阿斯利康建立了业内最多样化的产品组合和研发管线之一，有望催化医学实践的变革，并改善患者的治疗体验。

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

阿斯利康有重新定义癌症治疗并最终消除癌症致死的愿景。

AstraZeneca

阿斯利康

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology.

阿斯利康（LSE/STO/Nasdaq：AZN）是一家全球领先的、以科学为导向的生物制药公司，专注于肿瘤学、罕见病以及包括心血管、肾病与代谢、呼吸与免疫在内的生物制药领域的处方药的发现、开发和商业化。

Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca..

总部位于英国剑桥的阿斯利康公司的创新药物在全球 125 个国家销售，供全球数百万患者使用。请访问 astrazeneca.com 并在社交媒体上关注该公司 @AstraZeneca。

Contacts

联系人

For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.

如需了解如何联系投资者关系团队的详细信息，请点击这里。如需联系媒体，请点击这里。

References

参考文献

Source: astrazeneca.com

来源：astrazeneca.com