在BEGONIA Ib/II期试验中,Datopotamab deruxtecan + Imfinzi在一线治疗转移性三阴性乳腺癌患者中显示出稳健和持久的肿瘤反应

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)显示,在先前未经治疗的晚期或转移性三阴性乳腺癌(TNBC)患者中,联合用药显示出持久的肿瘤反应,并且没有新的安全性信号,从先前的数据截止日期起进行了6个月的额外随访.

这些数据将于今天在马德里举行的欧洲肿瘤医学学会(ESMO) 2023年大会的一个小型口头会议上公布, 西班牙(379莫).

Datopotamab deruxtecan是澳门在线赌城娱乐(澳门在线赌城娱乐)和第一三共(第一三共制药)联合开发的一种特异性工程的trop2导向的DXd抗体药物偶联物(ADC).

大约有300,000 people worldwide are diagnosed annually with TNBC, 最具侵袭性的乳腺癌亚型.1-2 不到一半的转移性TNBC患者对目前的一线治疗方案有反应,这些治疗方案包括单独化疗或联合免疫治疗.2-4 Among patients with tumours that do respond to initial treatment, 疾病进展普遍且迅速, 常发生在两年内的.2,4-6

Results showed that datopotamab deruxtecan plus Imfinzi, 抗pd - l1治疗, 证实客观缓解率(ORR)为79% (n=49 / 62),包括6个完全缓解(cr)和43个部分缓解(pr)。. Responses were observed regardless of PD-L1 expression level. 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, datopotamab deruxtecan联合durvalumab治疗一线三阴性乳腺癌的结果非常令人鼓舞, 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, Chief Medical Officer and Oncology Chief Development Officer, 澳门在线赌城娱乐, 他说:“多年来,一线晚期三阴性乳腺癌的进展一直很缓慢,需要新的治疗策略来改善这种侵袭性乳腺癌亚型患者的预后. 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, 澳门第一赌城在线娱乐急切地等待正在进行的III期三阴性乳腺癌项目的结果.”

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, underscoring the need for more durable treatment options. 这些发现显示了datopotamab deruxtecan在以前未治疗的晚期三阴性乳腺癌和乳腺癌中的潜力, following the positive results of our TROPION-Breast01 Phase III trial, 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.”

The safety profile of datopotamab deruxtecan in combination with Imfinzi was consistent with the known safety profiles of both agents. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 57% of patients. The most common Grade 3 or higher TEAEs were increased amylase (18%), 口腔炎(11%), 便秘(2%), 疲劳(2%), 呕吐(2%)和食欲下降(2%). 有3例间质性肺疾病(ILD)事件被独立委员会判定为与药物相关,包括2例2级事件和1例1级事件.

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%). Seven patients had tumours with high PD-L1 expression (TAP ≥10%). As of the 2 February 2023 data cut-off, 29 patients (47%) remained on study treatment.
 

海棠7臂疗效总结

Efficacy Measure (as assessed by investigator)

所有患者(n=62)

ORR,确认(95% CI)

79% (n=49) (66.8-88.3)

CR rate  

10% (n=6)

PR rate

69% (n=43)

中位DoR (95% CI)

15.5个月(9.9-not计算)

中位PFS (95% CI)

13.8个月(11).0-not计算)

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 is (complete response + partial response)


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 在未接受抗pd - l1治疗的局部复发性不能手术或转移性TNBC患者中,是否比较datopotamab deruxtecan与化疗. TROPION-Breast03 is evaluating datopotamab deruxtecan with and without 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.

ESMO 2023年大会上的几场演讲展示了datopotamab deruxtecan在多种肿瘤类型和环境中的数据强度和深度, including results from the TROPION-Lung01 and TROPION-Breast01 Phase III trials.

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

While some breast cancers may test positive for oestrogen receptors, 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 Approximately 15% of breast cancer tumours (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 晚期或转移性TNBC的一线治疗通常包括单独化疗或联合免疫治疗,这些方案的反应率通常在30%至50%之间.2-4 Among patients with tumours that do respond to initial treatment, 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, with only about 12% of patients living five years following diagnosis.7-8

TROP2 is a protein broadly expressed in several solid tumours, including TNBC.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 is an open-label, two-part, multicentre Phase Ib/II trial evaluating 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, tolerability and preliminary efficacy of datopotamab deruxtecan (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. The primary endpoints are safety and tolerability. Secondary endpoints are investigator-assessed ORR, PFS and DOR.

Enrolment is currently underway for Arm 8 of the BEGONIA trial, which is evaluating datopotamab deruxtecan plus Imfinzi in patients with TNBC whose tumours have high levels of PD-L1 expression.

Dato-DXd (Dato-DXd)
Dato-DXd (Dato-DXd) is an investigational TROP2-directed ADC. Designed using 第一三共制药’s proprietary DXd ADC technology, 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, and one of the most advanced programmes in 澳门在线赌城娱乐’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd)通过基于四肽的可切割连接体.

一项名为TROPION的综合开发项目正在全球范围内进行,有超过12项试验评估datopotamab deruxtecan治疗多种trop2靶向肿瘤的疗效和安全性, 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. 澳门在线赌城娱乐也在研究一种潜在的诊断测试,以帮助识别最有可能从datopotamab deruxtecan治疗中获益的患者.

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, 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, 中国和世界上许多其他国家的广泛期小细胞肺癌(SCLC)的治疗基于CASPIAN III期试验. 此外, Imfinzi is approved in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON Phase III trial.

In addition to its indication in lung cancer, Imfinzi 也被批准与化疗(吉西他滨+顺铂)联合治疗局部晚期或转移性胆道癌(BTC),并与 Imjudo in unresectable hepatocellular carcinoma (HCC) in the US, EU, Japan and several other countries based on the TOPAZ-1 and HIMALAYA Phase III trials, 分别. Imfinzi 是否在少数国家被批准用于治疗晚期膀胱癌患者.  

Since the first approval in May 2017, more than 200,000 patients have been treated with 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, several gastrointestinal cancers and other solid tumours.

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, except in Japan where 第一三共制药 maintains exclusive rights for each ADC. 第一三共制药 is responsible for the manufacturing and supply of Enhertu 和datopotamab deruxtecan.

澳门在线赌城娱乐治疗乳腺癌
Driven by a growing understanding of breast cancer biology, 澳门在线赌城娱乐开始挑战, 并重新定义, 目前的临床模式是如何对乳腺癌进行分类和治疗,以便为有需要的患者提供更有效的治疗,并怀着有朝一日消除乳腺癌这一致死原因的大胆雄心.

澳门在线赌城娱乐拥有全面的已批准和有前景的化合物组合,利用不同的作用机制来解决生物多样性的乳腺癌肿瘤环境.

With Enhertu (曲妥珠单抗deruxtecan), her2定向ADC, 澳门在线赌城娱乐和第一三共制药的目标是改善先前治疗的her2阳性和her2低转移性乳腺癌的预后,并正在探索其在早期治疗线和新发乳腺癌中的潜力.

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 新一代SERD、潜在新药camizestrant以及潜在的一流AKT激酶抑制剂将重塑hr阳性领域, 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 奥拉帕尼(olaparib)是一种靶向治疗方案,已经在具有遗传性BRCA突变的早期和转移性乳腺癌患者中进行了研究. 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 in these settings and to explore its potential in earlier disease.

To bring much-needed treatment options to patients with triple-negative breast cancer, 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 in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including 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, 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. 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 has the vision to redefine cancer care and, 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, science-led biopharmaceutical company that focuses on the discovery, 发展, and commercialisation of prescription medicines in Oncology, 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.

联系人
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参考文献

1. 宋海,等. 全球癌症统计2020:GLOBOCAN估计全球185个国家36种癌症的发病率和死亡率. 癌症J临床. 2021; 10.3322 /民航总局.21660.

2. O 'Reilly D等. Overview of recent advances in metastatic triple negative breast cancer. 世界临床肿瘤学杂志. 2021;12(3): 164-182.

3. Bergin A, et al. 三阴性乳腺癌: recent treatment advances. F1000Res. 2019; 8:10.12688 / f1000research.18888.1.

4. 张勇,等. Genomic features of rapid versus late relapse in triple negative breast cancer. BMC癌症. 2021; 21(568).

5. Cortes J,等. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. [英]医学. 2022; 387: 217-226. 10.1056 / NEJMoa2202809.

6. Emans L,等. Atezolizumab和nab-紫杉醇治疗晚期三阴性乳腺癌:IMpassion130研究的生物标志物评估. 美国国立癌症研究所. 2021; 113(8): djab004.

7. 国家癌症研究所. Surveillance, Epidemiology and End Results Program. 可以在: http://seer.cancer.gov / statfacts / html / breast-subtypes.html. 2023年10月生效.  

8. Sharma P,等. Biology and Management of Patients with Triple-Negative Breast Cancer. 肿瘤学家. 2016; 21(9): 1050-62. 10.1634 / theoncologist.2016-0067.

9. 林海,等. TACSTD2和Cyclin D1的显著上调与浸润性导管性乳腺癌预后不良相关. Exp Mol Pathol. 2013;94(1):73-8.

10. Goldenberg D等. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget. 2018;9(48): 28989-29006.


tags

  • Oncology
  • 公司和金融