Datopotamab deruxtecan plus Imfinzi demonstrated robust and durable tumour responses in 1st-line treatment of patients with metastatic triple-negative breast cancer in BEGONIA Phase Ib/II trial

澳门在线赌城娱乐和第一三共制药的datopotamab deruxtecan + Imfinzi证实客观缓解率为79%

两项正在进行的III期试验正在评估datopotamab deruxtecan对三阴性乳腺癌患者的疗效

来自BEGONIA Ib/II期临床试验的最新结果，该试验的患者接受datopotamab deruxtecan (Dato-DXd) +治疗 Imfinzi (durvalumab) (Arm 7) showed that the combination demonstrated durable tumour responses and no new safety signals in patients with previously untreated advanced or metastatic triple-negative breast cancer (TNBC) with six months additional follow-up from the previous data cut-off.

These data will be presented today in a mini oral session at the European Society for Medical 肿瘤学 (ESMO) 2023 Congress in Madrid, 西班牙(379莫).

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by 澳门在线赌城娱乐 and 第一三共制药.

大约有300,全世界每年有000人被诊断为三阴癌, 最具侵袭性的乳腺癌亚型.^1-2 Less than half of patients with metastatic TNBC respond to current 1st-line treatment options which can include chemotherapy alone or in combination with an immunotherapy.^2-4 在对初始治疗有反应的肿瘤患者中, 疾病进展普遍且迅速, 常发生在两年内的.^2,4-6

结果显示，datopotamab deruxtecan + Imfinzi, 抗pd - l1治疗, demonstrated a confirmed objective response rate (ORR) of 79% (n=49 of 62) including six complete responses (CRs) and 43 partial responses (PRs). 无论PD-L1表达水平如何，均观察到反应. 中位无进展生存期(PFS)为13.8个月(95%可信区间[CI] 11-不可计算[NC])，中位反应持续时间(DoR)为15.5个月(95% CI: 9.9-NC)与11.随访7个月.

彼得•施密德, MD, 巴茨癌症研究所, London, 联合王国, 也是试验的调查员, said: “These results for datopotamab deruxtecan plus durvalumab in the first-line triple-negative breast cancer setting are highly encouraging, 特别是79%的客观反应率. 考虑到该队列中大多数患者患有低pd - l1肿瘤，这种反应程度尤其值得注意, 代表了长期以来只能接受标准化疗的人群.”

克里斯蒂安·Massacesi, 首席医疗官和肿瘤学首席发展官, 澳门在线赌城娱乐, said: “Progress in the first-line advanced triple-negative breast cancer setting has been modest for years and new therapeutic strategies are needed to improve outcomes for patients with this aggressive breast cancer subtype. 这些来自BEGONIA试验的最新结果增强了澳门第一赌城在线娱乐对datopotamab deruxtecan成为一种新型治疗药物潜力的信心, important treatment modality 在这种情况下 as we eagerly await results from our ongoing Phase III triple-negative breast cancer programme.”

马克Rutstein, MD, 全球主管, 肿瘤临床发展, 第一三共制药, 他说:“对于三阴性乳腺癌患者来说，最初治疗后疾病进展是一个现实, 强调需要更持久的治疗方案. These findings showcase the potential of datopotamab deruxtecan in previously untreated advanced triple-negative breast cancer and, 在澳门第一赌城在线娱乐的TROPION-Breast01 III期试验取得积极结果之后, 以越来越多的证据为基础，证明这种trop2导向抗体药物偶联物的潜在用途, 单独或组合, 在乳腺癌的几个亚型中.”

datopotamab deruxtecan与 Imfinzi 是否与两种药物已知的安全性相符. 57%的患者出现了3级或更高级别的治疗不良事件(teae). 最常见的3级或以上teae是淀粉酶升高(18%)。, 口腔炎(11%), 便秘(2%), 疲劳(2%), 呕吐(2%)和食欲下降(2%). There were three interstitial lung disease (ILD) events adjudicated as drug-related by an independent committee including two Grade 2 events and one Grade 1 event.

BEGONIA试验的第7组(n=62), the majority of patients (n=54) had tumours with low PD-L1 expression (tumour area positivity [TAP] <10%). 7例患者肿瘤PD-L1高表达(TAP≥10%). 截至2023年2月2日数据截止，29名患者(47%)仍在接受研究治疗.
 

海棠7臂疗效总结

CR; complete response; CI, confidence interval; DCR, disease control rate; ORR, objective response rate; PR, partial response; PD, progressive disease; SD, 稳定的疾病
ⁱ ORR为(完全响应+部分响应)

澳门在线赌城娱乐和第一三共制药正在进行两项III期试验，评估datopotamab deruxtecan在TNBC中的治疗效果. TROPION-Breast02 is comparing datopotamab deruxtecan to chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic TNBC who are not candidates for anti-PD-L1 therapy. TROPION-Breast03 评估datopotamab是否有或没有deruxtecan Imfinzi 与研究者对新辅助治疗后伴有残留疾病的I-III期TNBC患者的治疗选择.

Several presentations featured during the ESMO 2023 Congress are showcasing the strength and depth of data for datopotamab deruxtecan across multiple tumour types and settings, 包括TROPION-Lung01和TROPION-Breast01 III期试验的结果.

Notes

三阴性乳腺癌
乳腺癌是世界上最常见的癌症，也是癌症相关死亡的主要原因.¹ 2020年，全球诊断出200多万例乳腺癌病例，近68.5万人死亡.¹

虽然有些乳腺癌雌激素受体检测呈阳性, 孕酮受体或人表皮生长因子受体2 (HER2)过表达, 三阴癌都呈阴性.² 大约15%的乳腺癌肿瘤(300,每年000例)被认为是三阴性，这是最具侵略性的乳腺癌亚型.^1-2 1st-line treatment for advanced or metastatic TNBC usually consists of chemotherapy alone or in combination with an immunotherapy – options generally associated with response rates between 30 to 50%.^2-4 在对初始治疗有反应的肿瘤患者中, 疾病进展普遍且迅速, 常发生在两年内的.^2,4-6 晚期或转移性TNBC患者的平均总生存期为12至18个月, 只有12%的患者在确诊后能活五年.^7-8

TROP2是一种在包括TNBC在内的几种实体肿瘤中广泛表达的蛋白.⁹ 在乳腺癌患者中，TROP2与肿瘤进展增加和生存率降低有关.^9-10

BEGONIA
BEGONIA 一项开放标签、两部分、多中心的Ib/II期试验是否评估 Imfinzi 与紫杉醇或不含紫杉醇的肿瘤治疗联合用于转移性TNBC的一线治疗. 该试验的第7组正在评估安全性, datopotamab deruxtecan的耐受性和初步疗效(6).0 mg/kg)与 Imfinzi (1120 mg)用于以前未治疗、不可切除的局部晚期或转移性TNBC患者. 主要终点是安全性和耐受性. 次要终点是研究者评估的ORR、PFS和DOR.

目前正在进行BEGONIA试验第8期的招募, 哪个是评估datopotamab deruxtecan + Imfinzi 肿瘤中PD-L1表达水平高的TNBC患者.

Dato-DXd (Dato-DXd)
Dato-DXd (Dato-DXd)是一种实验性的trop2导向ADC. 采用第一三共制药专有的DXd ADC技术设计, datopotamab deruxtecan是第一三共(第一三共制药)肿瘤产品线中的六个先导adc之一, 也是澳门在线赌城娱乐ADC科学平台中最先进的项目之一. Datopotamab deruxtecan由人源抗trop2 IgG1单克隆抗体组成, 与札幌医科大学合作开发, 附着在一些拓扑异构酶I抑制剂有效载荷上(一种艾替替康衍生物), DXd)通过基于四肽的可切割连接体.

A comprehensive 发展 programme called TROPION is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple TROP2-targetable tumours, 包括非小细胞肺癌(NSCLC), TNBC和hr阳性, her2低或阴性乳腺癌. 在TROPION项目之外, 在几个正在进行的试验中，Datopotamab deruxtecan也正在以新的组合进行评估. 澳门在线赌城娱乐 is also researching a potential diagnostic test to help identify patients most likely to benefit from treatment with datopotamab deruxtecan.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, 对抗肿瘤的免疫逃避策略，释放对免疫反应的抑制.

Imfinzi 在治疗目的为不可切除的情况下，唯一批准的免疫疗法和全球护理标准是不可切除的吗, 基于PACIFIC III期试验的III期NSCLC患者在放化疗后病情未进展.

Imfinzi 在美国也被批准了吗, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer (SCLC) based on the CASPIAN Phase III trial. 此外, Imfinzi 与短期疗程的 Imjudo (tremelimumab)和化疗在美国用于治疗转移性NSCLC, 欧盟和日本基于POSEIDON III期试验.

除了肺癌的适应症， Imfinzi is also approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer (BTC) and in combination with Imjudo 在不可切除的肝细胞癌(HCC)中, EU, 日本和其他几个国家基于TOPAZ-1和HIMALAYA III期试验, 分别. Imfinzi 是否在少数国家被批准用于治疗晚期膀胱癌患者.  

自2017年5月首次获批以来，已有超过20万名患者接受了治疗 Imfinzi.

作为广泛发展计划的一部分， Imfinzi 是否在SCLC患者的单独治疗和联合其他抗癌治疗中进行测试, NSCLC, 膀胱癌, 一些胃肠道癌症和其他实体肿瘤.

第一三共合作
澳门在线赌城娱乐和第一三共进入全球合作，共同开发和商业化 Enhertu in 2019年3月 和datopotamab deruxtecan 2020年7月在日本，第一三共维持每个ADC的专有权. 第一三共制药负责生产和供应 Enhertu 和datopotamab deruxtecan.

澳门在线赌城娱乐治疗乳腺癌
由于对乳腺癌生物学的了解越来越深入, 澳门在线赌城娱乐开始挑战, 并重新定义, 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.

澳门在线赌城娱乐 has a comprehensive portfolio of approved and promising compounds in 发展 that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

With Enhertu (曲妥珠单抗deruxtecan), her2定向ADC, 澳门在线赌城娱乐 and 第一三共制药 are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

在hr阳性乳腺癌中，澳门在线赌城娱乐继续通过基础药物改善预后 Faslodex (fulvestrant)和 Zoladex (goserelin) and aims to reshape the HR-positive space with next-generation SERD and potential new medicine camizestrant as well as a potential first-in-class AKT kinase inhibitor, capivasertib. 澳门在线赌城娱乐还与第一三共制药合作，探索trop2导向ADC的潜力, datopotamab deruxtecan, 在这种情况下.

PARP抑制剂 Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. 澳门在线赌城娱乐与默沙东 & Co., Inc. 在美国和加拿大)继续研究 Lynparza 并探索其在早期疾病中的潜力.

为三阴性乳腺癌患者提供急需的治疗选择, 一种侵袭性乳腺癌, 澳门在线赌城娱乐正在评估datopotamab deruxtecan单独和联合免疫疗法的潜力 Imfinzi (durvalumab)， capivasertib联合化疗，以及 Imfinzi 与其他肿瘤药物联合使用，包括 Lynparza and Enhertu.

澳门在线赌城娱乐在肿瘤学
澳门在线赌城娱乐正在引领肿瘤学领域的一场革命，致力于为各种形式的癌症提供治疗, 跟随科学去了解癌症及其所有的复杂性, 开发并向患者提供改变生活的药物.

该公司专注于一些最具挑战性的癌症. 正是通过持续的创新，澳门在线赌城娱乐建立了行业中最多样化的产品组合和管道之一, 有可能催化医学实践的变化，改变病人的体验.

澳门在线赌城娱乐的愿景是重新定义癌症治疗和, one day, 消除癌症作为死亡原因.

澳门在线赌城娱乐
澳门在线赌城娱乐(LSE/STO/Nasdaq: AZN)是一家全球性制药公司, 以科学为主导的澳门第一赌城在线娱乐公司，专注于发现, 发展, 以及肿瘤学处方药的商业化, 罕见疾病, 和澳门第一赌城在线娱乐, 包括心血管, Renal & 新陈代谢和呼吸 & 免疫学. 总部设在剑桥, UK, 澳门在线赌城娱乐在100多个国家开展业务，其创新药物被全球数百万患者使用. 请访问 澳门在线赌城娱乐.com 并在社交媒体上关注公司 @澳门在线赌城娱乐.

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