Based on ECHO Phase III trial which demonstrated Calquence combination reduced risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy

基于ECHO III期临床试验，该试验表明，与标准护理化学免疫疗法相比，联合用药可将疾病进展或死亡的风险降低27%

Submission to be reviewed under Project Orbis

Orbis项目下待审查的提交文件

AstraZeneca’s supplemental New Drug Application (sNDA) for Calquence (acalabrutinib) has been accepted and granted Priority Review in the US for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL).

阿斯利康针对Calquence（acalabrutinib）的补充新药申请（sNDA）已在美国被接受并获得优先审查，用于治疗先前未经治疗的套细胞淋巴瘤（MCL）的成年患者。

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the first quarter of 2025..

美国食品和药物管理局（FDA）优先审查药物申请，如果获得批准，将通过证明安全性或有效性改进，预防严重疾病或提高患者依从性，从而显着改善现有选择。1处方药用户费用法案日期，即FDA监管决定的行动日期，预计在2025年第一季度。。

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), resulting when B-lymphocytes mutate into malignant cells within a region of the lymph node known as the mantle zone.2,3 The disease is often diagnosed at advanced stages and remains largely incurable. It is estimated that there are more than 27,500 people living with MCL worldwide.4,5.

MCL是一种罕见且典型的侵袭性非霍奇金淋巴瘤（NHL），当B淋巴细胞在称为套区的淋巴结区域内突变为恶性细胞时产生[2,3]。该疾病通常被诊断为晚期，并且仍然无法治愈。据估计，全世界有超过27500人患有MCL。4,5。

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Today’s Priority Review acceptance reinforces the potential of Calquence to transform outcomes in untreated mantle cell lymphoma. Data from the ECHO trial showed Calquence plus chemoimmunotherapy significantly delayed disease progression and showed a trend to improved survival in patients with this currently incurable blood cancer.

阿斯利康肿瘤研发执行副总裁苏珊·加尔布雷斯（SusanGalbraith）表示：“今天的优先审查认可增强了Calquence改变未经治疗的套细胞淋巴瘤预后的潜力。ECHO试验的数据显示，Calquence加化学免疫疗法显着延缓了疾病进展，并显示出改善这种目前无法治愈的血癌患者生存率的趋势。

We are working closely with the FDA to provide patients this potential new treatment as soon as possible.”.

我们正在与FDA密切合作，尽快为患者提供这种潜在的新疗法。”。

The sNDA is being reviewed under Project Orbis, an initiative of the FDA which provides a framework for concurrent submission and review of oncology medicines among participating international partners to bring cancer treatments to patients around the world as early as possible.

sNDA正在Orbis项目下进行审查，该项目是FDA的一项举措，为参与的国际合作伙伴同时提交和审查肿瘤药物提供了一个框架，以尽早将癌症治疗带给世界各地的患者。

Results from the ECHO Phase III trial recently were presented during the late-breaking oral session at the European Hematology Association (EHA) 2024 Hybrid Congress.

ECHO III期试验的结果最近在欧洲血液学协会（EHA）2024年混合大会的晚期口腔会议上发表。

In the trial, Calquence plus bendamustine and rituximab reduced the risk of disease progression or death by 27% compared to standard-of-care (SoC) chemoimmunotherapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.57-0.94; p=0.016). The addition of Calquence to SoC provided almost 1.5 years of additional median progression free survival (mPFS) with mPFS of 66.4 months for patients treated with the Calquence combination versus 49.6 months with SoC..

在该试验中，与标准治疗（SoC）化学免疫疗法相比，Calquence加苯达莫司汀和利妥昔单抗可将疾病进展或死亡风险降低27%（风险比[HR]0.73；95%置信区间[CI]0.57-0.94；p=0.016）。将Calquence添加到SoC中可为接受Calquence联合治疗的患者提供近1.5年的额外中位无进展生存期（mPFS），mPFS为66.4个月，而SoC为49.6个月。。

Overall survival (OS) showed a favourable trend for the Calquence combination compared to SoC chemoimmunotherapy (HR 0.86; 95% CI 0.65-1.13; p=0.2743). The OS trend was sustained over time, although most patients in the SoC arm who needed subsequent therapy received a BTK inhibitor, mainly Calquence.

与SoC化学免疫疗法相比，Calquence组合的总生存率（OS）显示出有利的趋势（HR 0.86；95%CI 0.65-1.13；p=0.2743）。随着时间的推移，OS趋势持续存在，尽管SoC组中大多数需要后续治疗的患者接受了BTK抑制剂，主要是Calquence。

The OS data were not mature at the time of this analysis, and the trial will continue to assess OS as a key secondary endpoint..

在进行此分析时，操作系统数据还不成熟，该试验将继续评估操作系统作为关键的次要终点。。

The ECHO trial was conducted during the COVID-19 pandemic, and prespecified PFS and OS analyses censoring for COVID-19 deaths were conducted to assess the impact of COVID-19 on the study outcome in alignment with FDA. After censoring for COVID-19 deaths, the PFS was further improved in both arms, with the Calquence combination reducing the risk of disease progression or death by 36% (HR 0.64; 95% CI; 0.48-0.84; p=0.0017).

ECHO试验是在COVID-19大流行期间进行的，并进行了预先指定的PFS和OS分析，对COVID-19死亡进行了审查，以评估COVID-19对FDA研究结果的影响。在对COVID-19死亡进行检查后，两组的PFS均得到进一步改善，联合用药可将疾病进展或死亡风险降低36%（HR 0.64；95%CI；0.48-0.84；p=0.0017）。

A favourable trend was seen for OS in this analysis for the Calquence combination, but OS data were not mature at the time of this analysis (HR 0.75; 95% CI 0.53-1.04; p=0.0797)..

在该分析中，对于计算序列组合，OS呈现出有利的趋势，但在进行该分析时，OS数据尚不成熟（HR 0.75；95%CI 0.53-1.04；p=0.0797）。。

The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified.

Calquence的安全性和耐受性与其已知的安全性一致，并且没有发现新的安全信号。

Notes

注释

MCL

MCL

While MCL patients initially respond to treatment, patients do tend to relapse.6 MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; in the US, it is estimated that approximately 4,000 new patients are diagnosed with MCL each year.6,7.

虽然MCL患者最初对治疗有反应，但患者确实倾向于复发[6]。MCL约占非霍奇金淋巴瘤的3-6%，西方国家每10万人年发病率为0.5；在美国，估计每年约有4000名新患者被诊断出患有MCL[6,7]。

ECHO

回声

ECHO is a randomised, double-blind, placebo-controlled, multi-centre Phase III trial evaluating the efficacy and safety of Calquence plus bendamustine and rituximab compared to SoC chemoimmunotherapy (bendamustine and rituximab) in adult patients at or over 65 years of age (n=635) with previously untreated MCL.8 Patients were randomised 1:1 to receive either Calquence or placebo administered orally twice per day, continuously, until disease progression or unacceptable toxicity.

ECHO是一项随机，双盲，安慰剂对照，多中心III期临床试验，评估Calquence加苯达莫司汀和利妥昔单抗与SoC化学免疫疗法（苯达莫司汀和利妥昔单抗）相比在65岁或65岁以上的成年患者中的疗效和安全性（n=635）以前未经治疗的MCL。8名患者被随机分为1:1，每天两次口服Calquence或安慰剂，连续服用，直到疾病进展或不可接受的毒性。

Additionally, all patients received six 28-day cycles of bendamustine on days 1 and 2 and rituximab on day 1 of each cycle, followed by rituximab maintenance for two years if patients achieved a response after induction therapy.8.

此外，所有患者在第1天和第2天接受6个28天周期的苯达莫司汀治疗，在每个周期的第1天接受利妥昔单抗治疗，如果患者在诱导治疗后获得反应，则利妥昔单抗维持两年。

The primary endpoint is PFS assessed by an Independent Review Committee; other efficacy endpoints include OS, overall response rate (ORR), duration of response (DoR) and time to response (TTR).8 The trial was conducted in 27 countries across North and South America, Europe, Asia and Oceania.8

主要终点是由独立审查委员会评估的PFS；其他疗效终点包括OS，总有效率（ORR），反应持续时间（DoR）和反应时间（TTR）[8]。该试验在南北美洲，欧洲，亚洲和大洋洲的27个国家进行

The ECHO trial enrolled patients from May 2017 to March 2023, continuing through the COVID-19 pandemic. Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalisation and death compared to the general population.9

ECHO试验从2017年5月至2023年3月招募了患者，持续到新型冠状病毒肺炎大流行。

Calquence

因果关系

Calquence (acalabrutinib) is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.10 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion..

Calquence（acalabrutinib）是布鲁顿酪氨酸激酶（BTK）的第二代选择性抑制剂。Calquence与BTK共价结合，从而抑制其活性。在B细胞中，BTK信号传导导致B细胞增殖，运输，趋化性和粘附所必需的途径的激活。。

Calquence has been used to treat more than 85,000 patients worldwide11 and is approved for the treatment of CLL and small lymphocytic lymphoma (SLL) in the US and Japan, approved for CLL in the EU and many other countries worldwide and approved in China for relapsed or refractory CLL and SLL. Calquence is also approved in the US, China and several other countries for the treatment of adult patients with MCL who have received at least one prior therapy.

Calquence已被用于治疗全球超过85000名患者11，并在美国和日本被批准用于治疗CLL和小淋巴细胞淋巴瘤（SLL），在欧盟和全球许多其他国家被批准用于CLL，并在中国被批准用于复发或难治性CLL和SLL。Calquence在美国，中国和其他几个国家也被批准用于治疗至少接受过一次治疗的成年MCL患者。

Calquence is not currently approved for the treatment of MCL in Japan or the EU..

Calquence目前尚未在日本或欧盟批准用于治疗MCL。。

As part of an extensive clinical development programme, Calquence is currently being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancers, including CLL, MCL, and diffuse large B-cell lymphoma.

作为广泛临床开发计划的一部分，Calquence目前正在作为单一治疗方法进行评估，并与多种B细胞血癌（包括CLL，MCL和弥漫性大B细胞淋巴瘤）患者的标准护理化学免疫疗法相结合。

AstraZeneca in haematology

阿斯利康血液学

AstraZeneca is pushing the boundaries of science to redefine care in haematology. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases through innovative medicines and approaches that are shaped by insights from patients, caregivers and physicians..

阿斯利康正在推动科学界重新定义血液学护理。我们的目标是通过患者、护理人员和医生的见解形成的创新药物和方法，帮助改变恶性、罕见和其他相关血液疾病患者的生活。。

In addition to our marketed products, we are spearheading the development of novel therapies designed to target underlying drivers of disease across multiple scientific platforms. Our acquisitions of Alexion, with expertise in rare, non-malignant blood disorders, and Gracell Biotechnologies Inc., pioneers of autologous cell therapies, expand our haematology pipeline and enable us to reach more patients with high unmet needs through the end-to-end discovery, development and delivery of novel therapies..

除了我们销售的产品外，我们还率先开发新疗法，旨在跨多个科学平台针对疾病的潜在驱动因素。我们收购了在罕见的非恶性血液疾病方面具有专业知识的亚力兄和Gracell Biotechnologies Inc.，自体细胞疗法的先驱，扩大了我们的血液学渠道，使我们能够通过端到端的发现，开发和提供新疗法来接触更多未满足需求的患者。。

AstraZeneca in oncology

阿斯利康肿瘤学

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（AstraZeneca）正在领导一场肿瘤学革命，致力于为各种形式的癌症提供治疗，遵循科学理解癌症及其复杂性，发现、开发并向患者提供改变生命的药物。

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.

该公司专注于一些最具挑战性的癌症。正是通过不断的创新，阿斯利康建立了行业内最多样化的投资组合和渠道之一，有可能促进医学实践的变化并改变患者的体验。

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

阿斯利康的愿景是重新定义癌症护理，并有一天消除癌症作为死亡原因。

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）是一家全球科学领先的生物制药公司，专注于肿瘤学，罕见病和生物制药（包括心血管，肾脏和代谢以及呼吸和免疫学）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..

阿斯利康的创新药物总部位于英国剑桥，在125多个国家销售，全球数百万患者使用。请访问astrazeneca.com并在社交媒体@astrazeneca上关注该公司。。

Contacts

联系人

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

有关如何联系投资者关系团队的详细信息，请单击此处。有关媒体联系人，请单击此处。

References

参考文献

FDA. Priority Review. Available at: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review. Accessed September 2024.

FDA。优先审查。网址：https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.2024年9月访问。

Lymphoma Research Foundation. Mantle Cell Lymphoma. Available at: https://lymphoma.org/aboutlymphoma/nhl/mcl/. Accessed September 2024.

淋巴瘤研究基金会。套细胞淋巴瘤。网址：https://lymphoma.org/aboutlymphoma/nhl/mcl/.2024年9月访问。

National Organization for Rare Disorders. Mantle Cell Lymphoma. Available at: https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/. Accessed September 2024.

国家罕见疾病组织。套细胞淋巴瘤。网址：https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/.2024年9月访问。

GLOBOCAN. Non-Hodgkin Lymphoma. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/34-non-hodgkin-lymphoma-fact-sheet.pdf. Accessed September 2024.

GLOBOCAN公司。非霍奇金淋巴瘤。网址：https://gco.iarc.who.int/media/globocan/factsheets/cancers/34-non-hodgkin-lymphoma-fact-sheet.pdf.2024年9月访问。

Lynch DT, Koya S, Acharya U, et al. Mantle Cell Lymphoma. Available at: https://www.ncbi.nlm.nih.gov/books/NBK536985/. Accessed September 2024.

Lynch DT，Koya S，Acharya U等。套细胞淋巴瘤。网址：https://www.ncbi.nlm.nih.gov/books/NBK536985/.2024年9月访问。

Cheah C, Seymour J, Wang ML. Mantle cell lymphoma. J Clin Oncol. 2016;34(11):1256-1269. doi: 10.1200/JCO.2015.63.5904.

Cheah C，Seymour J，Wang ML.套细胞淋巴瘤。J临床肿瘤学。2016年；34（11）：1256-1269。doi:10.1200/JCO.2015.63.5904。

MD Anderson Cancer Center. What to know about mantle cell lymphoma. Available at: https://www.mdanderson.org/cancerwise/what-to-know-about-mantle-cell-lymphoma-symptoms-diagnosis-and-treatment.h00-159385101.html. Accessed September 2024.

MD安德森癌症中心。关于套细胞淋巴瘤的知识。网址：https://www.mdanderson.org/cancerwise/what-to-know-about-mantle-cell-lymphoma-symptoms-diagnosis-and-treatment.h00-159385101.html.2024年9月访问。

ClinicalTrials.gov. A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL. Available at: https://clinicaltrials.gov/study/NCT02972840. Accessed September 2024.

ClinicalTrials.gov。对先前未经治疗的MCL患者单独使用BR与联合使用阿卡鲁替尼的研究。网址：https://clinicaltrials.gov/study/NCT02972840.2024年9月访问。

Dube S, et al. Continued Increased Risk of COVID-19 Hospitalisation and Death in Immunocompromised Individuals Despite Receipt of ≥4 Vaccine Doses: Updated 2023 Results from INFORM, a Retrospective Health Database Study in England. Poster P0409 at ECCMID 2024.

Dube S等人。尽管接受了≥4剂疫苗，但免疫功能低下个体的新型冠状病毒肺炎住院和死亡风险持续增加：英格兰回顾性健康数据库研究INFORM的2023年更新结果。ECCMID 2024海报P0409。

Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).

Wu J，Zhang M，Liu D.Acalabrutinib（ACP-196）：一种选择性第二代BTK抑制剂。J Hematol Oncol。2016年；9（21）。

Data on File, REF-236261. AstraZeneca Pharmaceuticals LP.

文件中的数据，REF-236261。阿斯利康制药有限公司。