Lynparza and Imfinzi demonstrated strong clinical benefit and more than doubled median duration of response vs. chemotherapy in patients with mismatch repair proficient advanced or recurrent endometrial cancer

Clinical benefit with Imfinzi was greatest in the mismatch repair deficient subgroup

Results from the DUO-E trial reinforce potential of both Imfinzi and the
Lynparza and Imfinzi regimen in endometrial cancer
 

Latest analysis of the results from the DUO-E Phase III trial showed Imfinzi (durvalumab) plus platinum-based chemotherapy followed by Imfinzi plus Lynparza (olaparib) (Lynparza and Imfinzi arm) demonstrated an improvement in multiple key secondary efficacy endpoints, 特别是在错配修复熟练(pMMR)晚期或复发子宫内膜癌患者中，与单独化疗相比.

这些结果将于今天在圣地亚哥举行的2024年妇科肿瘤学会(SGO)女性癌症年会上发表, California.

A post-hoc exploratory subgroup analysis assessed patients by mismatch repair (MMR) status, a biomarker of interest in endometrial cancer. In this analysis, median duration of response (DoR) in pMMR patients in the Lynparza and Imfinzi arm was more than double versus the control arm (18.7 months versus 7.6). Additional secondary endpoints showed consistent results for pMMR patients treated with Lynparza and Imfinzi, 与对照组相比，联合治疗组的第二次进展或死亡风险(PFS2)降低了32%(中位数未达到vs 19).5 months, HR 0.68; 95% confidence interval [CI] 0.48-0.95), and improvement in time to first and second subsequent treatments.

Imfinzi plus chemotherapy followed by Imfinzi monotherapy (Imfinzi arm) showed consistent benefit regardless of MMR status, with the greatest benefit observed in patients with mismatch repair deficient (dMMR) disease across all secondary endpoints, including objective response rate (ORR) (71.4%) and DoR (median not reached), versus the control arm (40.5% and 10.5 months, respectively).

In the overall trial population, results in the Lynparza and Imfinzi arm showed extended ORR and DoR, as well as consistently improved benefit in secondary endpoints, including overall survival (OS), time to first subsequent therapy (TFST), PFS2 and time to second subsequent therapy (TSST).

Hye Sook Chon, gynaecologic oncologist at the Moffitt Cancer Center in Tampa, Florida, and trial investigator, said, “Endometrial cancer diagnoses are rapidly rising, 然而，近年来，对于大约80%精通错配修复的晚期或复发性疾病患者，在推进新疗法方面几乎没有什么变化. DUO-E结果表明durvalumab加化疗后再加durvalumab治疗dMMR患者的益处，并为pMMR患者在该方案中加入奥拉帕尼提供了令人信服的证据.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said, “DUO-E results have shown that adding Imfinzi to chemotherapy delivers better outcomes for patients with advanced endometrial cancer. In addition, 为达到最佳临床效益的患者最大的未满足需求-那些错配修复熟练疾病-添加 Lynparza further enhances the effect of checkpoint inhibition in endometrial cancer.”

Interim OS data showed a favourable trend for the Imfinzi arm and Lynparza and Imfinzi arm compared to the control arm in the overall trial population, irrespective of mismatch repair status.

Summary of results: DUO-E

These data are consistent with the positive primary analysis presented last year, which showed that the Imfinzi arm and the Lynparza and Imfinzi 在整个试验人群中，与单独化疗相比，两组均显示出具有统计学意义和临床意义的PFS改善.

The safety profiles of both experimental regimens were manageable, well-tolerated and broadly consistent with the known profiles of the individual agents.^1,2

Regulatory filings for DUO-E have been accepted for review by regulatory authorities across the world including in the US, Europe and Japan.

Notes

Endometrial cancer
子宫内膜癌是一种高度异质性的疾病，起源于子宫内膜组织，在已经绝经的妇女中最常见, with the average age at diagnosis being over 60 years old.^3-6 It is the sixth most common cancer in women worldwide.⁷ Incidence and mortality of endometrial cancer are expected to increase by approximately 61% and 87% respectively (from 420,400 cases and 97,700 deaths in 2022 to 676,300 cases and 183,100 deaths) in 2050.^7,8

The majority of patients with endometrial cancer are diagnosed at an early stage of disease, where the cancer is confined to the uterus. They are typically treated with surgery and/or radiation, and the five-year survival rate is high (approximately 95%). Patients with advanced disease (Stage III-IV) usually have a much poorer prognosis, with the five-year survival rate falling to around 20-30%. Immunotherapy combined with chemotherapy is emerging as a new standard of care for advanced endometrial cancer, particularly for patients with dMMR disease, who make up approximately 20% of all patients with this type of cancer.^9,10 There remains a high unmet need for treatments for the remaining 80% of endometrial cancer patients with pMMR disease.^11,12

DUO-E
The DUO-E trial (GOG 3041/ENGOT-EN10) is a three-arm, randomised, double-blind, placebo-controlled, multicentre Phase III trial of 1st-line Imfinzi (durvalumab) plus platinum-based chemotherapy (carboplatin and paclitaxel) followed by either Imfinzi monotherapy or Imfinzi plus Lynparza (olaparib) 新诊断的晚期或复发子宫内膜癌患者的维持治疗与单纯铂基化疗的比较.

The DUO-E trial randomised 699 patients with newly diagnosed advanced or recurrent epithelial endometrial carcinoma to receive either Imfinzi (1120mg) or placebo, given every three weeks in addition to standard-of-care platinum-based chemotherapy. After 4-6 cycles of chemotherapy, patients (whose disease had not progressed) then received either Imfinzi (1500mg) or placebo every four weeks as maintenance, plus 300mg Lynparza (300mg BID [2x150mg tablets, twice a day]) or placebo until disease progression.

The dual primary endpoint was progression-free survival (PFS) of each treatment arm versus standard of care. Key secondary endpoints included overall survival (OS), safety and tolerability. Mismatch repair (MMR) status, recurrence status and geographic location were stratification factors. 错配修复缺陷(dMMR)状态反映了无法纠正DNA复制错误，因此导致癌症风险增加, 而错配修复精通(pMMR)状态表明DNA修复途径保持完整以及错配修复途径活跃和起作用的位置.^13,14 The trial was sponsored independently by AstraZeneca and conducted in 253 study locations across 22 countries including the US, Europe, South America and Asia.

For more information about the trial, please visit ClinicalTrials.gov.

Imfinzi
Imfinzi (durvalumab)是一种人单克隆抗体，结合PD-L1蛋白并阻断PD-L1与PD-1和CD80蛋白的相互作用, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is currently approved in a number of countries across multiple tumour types. Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage small-cell lung cancer (SCLC) and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC.

In addition to its indications in lung cancers, Imfinzi 被批准与化疗(吉西他滨加顺铂)联合治疗局部晚期或转移性胆道癌，并与 Imjudo in unresectable hepatocellular carcinoma. Imfinzi is also approved in previously treated patients with advanced bladder cancer in a small number of countries.

Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi. Imfinzi 也正在作为广泛开发项目的一部分进行测试，作为SCLC患者的单一治疗和与其他抗癌治疗的联合治疗, NSCLC, bladder cancer, breast cancer, ovarian cancer, several gastrointestinal cancers and other solid tumours.

Lynparza
Lynparza 是一种一流的PARP抑制剂，也是首个阻断同源重组相关(HRR)基因缺乏的细胞/肿瘤中的DNA损伤反应(DDR)的靶向治疗方法, such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents [NHAs]).

Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza may also help enhance immunogenicity and increase the impact of anti-tumour immune responses.

Lynparza is currently approved in a number of countries across multiple tumour types, 包括铂敏感复发卵巢癌的维持治疗，以及brca突变(BRCAm)和同源重组修复缺陷(HRD)阳性晚期卵巢癌的单药治疗和联合贝伐单抗一线维持治疗, respectively; for germline BRCA mutation (gBRCAm), HER2-negative metastatic breast cancer (in the EU and Japan, this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer (in Japan, this includes all BRCAm HER2-negative high-risk early breast cancer); for gBRCAm metastatic pancreatic cancer; in combination with abiraterone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) when chemotherapy is not clinically indicated (EU only) and for BRCAm mCRPC (US and Japan); and as monotherapy for HRR gene-mutated mCRPC in patients who have progressed on prior NHA treatment (BRCAm only in the EU and Japan). In China, Lynparza 被批准用于治疗brca突变的mCRPC以及贝伐单抗一线维持治疗hrd阳性晚期卵巢癌.

Lynparza is being jointly developed and commercialised by AstraZeneca and MSD, both as a monotherapy and in combination with other potential medicines. Independently, the companies are developing and will commercialise Lynparza in combination with their respective PD-L1 and PD-1 medicines, Imfinzi (durvalumab) and Keytruda (pembrolizumab). Lynparza has been used to treat approximately 140,000 patients worldwide. Lynparza has a broad clinical trial development programme, 澳门在线赌城娱乐和默沙东正在合作，以了解它如何作为单一疗法影响多种parp依赖性肿瘤，以及在多种癌症类型中联合使用. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. 该公司拥有全面和多样化的IO产品组合和管道，以免疫疗法为基础，旨在克服抗肿瘤免疫反应的逃避，并刺激人体免疫系统攻击肿瘤.

AstraZeneca aims to reimagine cancer care and help transform outcomes for patients with Imfinzi as monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. 该公司还在探索下一代免疫疗法，如双特异性抗体和利用免疫的不同方面来靶向癌症的疗法.

澳门在线赌城娱乐正在大胆地追求一种创新的临床策略，将基于io的治疗方法引入到各种癌症类型的新环境中，以实现长期生存. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.

AstraZeneca in oncology
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.

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.

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

AstraZeneca
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. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit chinaqinyu.com and follow the Company on social media @AstraZeneca.

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