澳门葡京网赌游戏和第一三共的掺tu显示中位无进展
6人生存.9个月，中位总生存期13.总共4个月
审判人口
结果重申了掺tu作为肿瘤不可知论治疗的潜在作用
治疗her2表达实体瘤患者，支持正在进行中
与全球监管机构进行讨论
正在进行的DESTINY-PanTumor02 II期试验初步分析的阳性结果表明 掺tu 曲妥珠单抗(trastuzumab deruxtecan)继续表现出临床意义和持久的反应, leading to a clinically meaningful survival benefit in previously treated patients across multiple HER2-expressing advanced solid tumours.
这些结果, 包括试验报告的首次无进展生存期(PFS)和总生存期(OS)结果, 该研究今天在马德里举行的2023年欧洲肿瘤医学学会(ESMO)大会上发表(摘要#LBA34), 并同时在西班牙出版 临床肿瘤学杂志.
掺tu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by 澳门葡京网赌游戏 and 第一三共制药.
在初步分析中， 掺tu PFS中位数为6.9个月(95%置信区间[CI] 5.6-8.0)，中位OS为13.4个月(95% CI 11.9-15.5)在既往治疗过的表达her2的晚期实体瘤患者的总体试验人群中, 包括胆道, 膀胱, 颈, 子宫内膜, 卵巢, 胰腺癌或其他肿瘤, 经调查人员评估. 掺tu 客观缓解率(ORR)为37.1%，中位反应持续时间(DoR)为11.3个月(95% CI 9.6-17.在这些病人中.
基础Meric-Bernstam, MD, 德克萨斯大学MD安德森癌症中心研究癌症治疗学主席, 他是该试验的首席研究员, 他说:“这些初步分析结果证实了DESTINY-PanTumor02试验中期分析显示的疗效, 在广泛的表达her2的实体肿瘤中产生具有临床意义的生存结果. 基于这些结果， 掺tu has the potential to change the course of disease for certain patients with HER2-expressing advanced 癌症s who have limited treatment options and currently no approved HER2-directed therapies.”
克里斯蒂安·Massacesi, 首席医疗官和肿瘤学首席发展官, 澳门葡京网赌游戏, said: “These updated data from DESTINY-PanTumor02 continue to illustrate the importance of HER2 as an actionable biomarker across a range of studied solid tumour types. 掺tu 有潜力提供吗 改善了先前接受过her2表达癌症治疗的特定患者的预后, 澳门葡京赌博游戏希望能尽快将这种重要的药物带给患者.”
马克Rutstein, MD, 全球主管, 肿瘤临床发展, 第一三共制药, said: “Improving survival outcomes for patients is one of the primary goals of 癌症 treatment and the clinically meaningful progression-free and overall survival results seen in DESTINY-PanTumor02 are encouraging. 这些结果提供了额外的证据 掺tu to potentially become the first antibody drug conjugate approved in a tumour-agnostic setting in patients whose tumours express HER2.”
结果总结:DESTINY-PanTumor02初步分析
疗效指标 |
子宫内膜
|
颈 |
卵巢
|
膀胱
|
其他i
|
BTC
|
胰腺 |
所有的病人 |
|---|---|---|---|---|---|---|---|---|
所有IHC表达水平 |
||||||||
(n) |
40 |
40 |
40 |
41 |
40 |
41 |
25 |
267 |
确认ORR (%) (95% CI) |
57.5% |
50.0% |
45.0% |
39.0% |
30.0% |
22.0% |
4.0% |
37.1% |
中位DoR(月)(95% CI) |
NR (9.9-NR) |
14.2 (4.1-NR) |
11.3 (4.1-22.1) |
8.7 (4.3-11.8) |
22.1 (4.1-NR) |
8.6 (2.1-NR) |
5.7 (NR-NR) |
11.3 (9.6-17.8) |
中位PFS(月)(95% CI) |
11.1 (7.1-NR) |
7.0 (4.2-11.1) |
5.9 (4.0-8.3) |
7.0 (4.2-9.7) |
8.8 (5.5-12.5) |
4.6 (3.1-6.0) |
3.2 (1.8-7.2) |
6.9 (5.6-8.0) |
中位OS(月)(95% CI) |
26.0 (12.8-NR) |
13.6 (11.1-NR) |
13.2 (8.0-17.7) |
12.8 (11.2-15.1) |
21.0 (12.9-24.3) |
7.0 (4.6-10.2) |
5.0 (3.8-14.2) |
13.4 (11.9-15.5) |
包含IHC 3 + |
||||||||
(n) |
13 |
8 |
11 |
16 |
9 |
16 |
2 |
75 |
确认ORR (%) (95% CI) |
84.6% |
75.0% |
63.6% |
56.3% |
44.4% |
56.3% |
0.0% |
61.3% |
中位DoR(月)(95% CI) |
|
|
|
|
|
|
|
22.1 (9.6-NR) |
中位PFS(月)(95% CI) |
NR (7.3-NR) |
NR (3.9-NR) |
12.5 (3.1-NR) |
7.4 (3.0-11.9) |
23.4 (5.6-NR) |
7.4 (2.8-12.5) |
5.4 (2.8-NR) |
11.9 (8.2-13.0) |
中位OS(月)(95% CI) |
26.0 (18.9-NR) |
NR (3.9-NR) |
20.0 (3.8-NR) |
13.4 (6.7-19.8) |
24.3 (11.1-NR) |
12.4 (2.8-NR) |
12.4 (8.8-NR) |
21.1 (15.3-29.6) |
包含IHC 2 + |
||||||||
(n) |
17 |
20 |
19 |
20 |
16 |
14 |
19 |
125 |
确认ORR (%) (95% CI) |
47.1% |
40.0% |
36.8% |
35.0% |
18.8% |
0.0% |
5.3% |
27.2% |
中位DoR(月)(95% CI) |
|
|
|
|
|
|
|
9.8 (4.3-12.6) |
中位PFS(月)(95% CI) |
8.5 (4.6-15.1) |
4.8 (2.7-5.7) |
4.1 (2.3-12.6) |
7.8 (2.6-11.6) |
5.5 (2.8-8.7) |
4.2 (2.8-6.0) |
2.8 (1.4-9.1) |
5.4 (4.2-6.0) |
中位OS(月)(95% CI) |
16.4 (8.0-NR) |
11.5 (5.1-NR) |
13.0 (4.7-21.9) |
13.1 (11.0-19.9) |
14.6 (6.8-22.4) |
6.0 (3.7-11.7) |
4.9 (2.4-15.7) |
12.2 (10.7-13.5) |
BTC, biliary tract 癌症; CI, confidence interval; DoR, duration of response; IHC, immunohistochemistry; NR, not reached; ORR, objective response rate; OS, overall survival; PFS, 无进展生存
Analysis of ORR by investigator was performed in patients who received ≥1 dose of T-DXd; all patients (n=267; including 67 patients with IHC 1+ [n=25], IHC 0 [n=30], or unknown IHC status [n=12] by central testing) and patients with centrally confirmed HER2 包含IHC 3 + (n=75) or 包含IHC 2 + (n=125) status.
Analysis of DoR was performed in patients with objective response who received ≥1 dose of T-DXd; all patients (n=99; including 19 patients with IHC 1+ [n=6], IHC 0 [n=9], or unknown IHC status [n=4] by central testing) and patients with centrally confirmed HER2 包含IHC 3 + (n=46) or 包含IHC 2 + (n=34) status.
i乳腺外佩吉特病的反应, 头颈癌, 口咽肿瘤, 还有唾液腺癌.
在DESTINY-PanTumor02试验的初步分析中, a greater response rate continued to be seen in patients with the highest level of HER2-expression (immunohistochemistry (IHC) 3+) as confirmed by central testing, 在哪里 掺tu 证实ORR为61.3% (95% CI: 49.4-72.4)作为探索性分析的一部分. 掺tu PFS中位数为11.9个月(95% CI: 8).2-13.0)，中位OS为21.1个月(95% CI: 15.3-29.6) 包含IHC 3 +肿瘤表达患者，DoR中位数为22.1个月(95% CI: 9.6-NR). 这些具有临床意义的结果强化了该试验中期分析的结果 提出了 在今年早些时候的2023年美国临床肿瘤学会年会上.
的安全概况 掺tu 是否与以前的临床试验一致，没有发现新的安全问题. 最常见的3级或更高级别治疗不良事件(teae)是中性粒细胞减少症(19.9).1%)，贫血(10%).9%)，疲劳(7%).1%)和血小板减少症(5%).6%).
在DESTINY-PanTumor02中，28例患者(10.5%)发生间质性肺疾病(ILD)或与治疗相关的肺炎 掺tu 由一个独立的裁决委员会决定. 大多数(9).0%)为低分级(1或2级)，1例(0.4%) 3级项目，无4级项目和3(1)级项目.1%)观察到5级事件.
笔记
实体瘤中HER2的表达
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.1,2 在某些癌症中，HER2表达扩增或细胞有激活突变.1,3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis.4
而her2定向疗法已被用于治疗乳腺癌, 胃, 肺癌和结直肠癌, 需要更多的研究来评估它们在治疗其他表达her2的实体肿瘤类型中的潜在作用.2,5,6
HER2是包括胆道在内的实体肿瘤类型的新兴生物标志物, 膀胱, 颈, 子宫内膜, 卵巢癌和胰腺癌.3 在这些额外的肿瘤类型中不常规进行检测，因此, 可用的文献有限. 在这些实体瘤中观察到HER2过表达(IHC3+)的比例为1%至28%.7,8 对某些表达her2的实体瘤的有效治疗还没有得到满足, particularly for those who have progressed on or are refractory to standard of care therapies as t在这里 are currently no approved HER2-directed therapies for these 癌症s.2,9
DESTINY-PanTumor02
DESTINY-PanTumor02是一个全球性的, 多中心, multi-cohort, 开放tagsII期试验评估的有效性和安全性 掺tu (5.4mg/kg)用于治疗先前治疗过的表达her2的肿瘤, 包括胆道癌, 膀胱癌, 子宫颈癌, 子宫内膜癌, 卵巢癌, 胰腺癌或其他肿瘤.
DESTINY-PanTumor02的主要疗效终点是研究者评估的确认ORR. 次要端点包括DoR, 疾病控制率, PFS, OS, 安全, 耐受性和药代动力学.
DESTINY-PanTumor02已经在亚洲、欧洲和北美的多个地点招募了267名患者. 有关该试验的更多信息，请访问 临床试验.政府.
掺tu
掺tu 是her2导向ADC吗. 采用第一三共制药专有的DXd ADC技术设计， 掺tu is the lead ADC in the oncology portfolio of 第一三共制药 and the most advanced programme in 澳门葡京网赌游戏’s ADC scientific platform. 掺tu 由附着在一些拓扑异构酶I抑制剂有效载荷上的HER2单克隆抗体组成, (一个exatecan衍生物, DXd)通过基于四肽的可切割连接rs.
掺tu (5.4mg/kg) is approved in more than 55 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast 癌症 who have received a (or one or more) prior anti-HER2-based regimen, 无论是在转移性情况下还是在新辅助或辅助情况下, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
掺tu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or 包含IHC 2 +/in-situ hybridisation [ISH]-) breast 癌症 who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
掺tu (5.4mg/kg) is approved in more than 30 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung 癌症 whose tumours have activating HER2 (ERBB2) mutations, 由当地或地区认可的检测检测到的, 并且根据DESTINY-Lung02试验的结果接受了先前的全身治疗. 继续d approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
掺tu (6.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive 胃 or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trial.
掺tu 发展计划
一项全面的临床开发计划正在全球范围内进行, 评价的有效性和安全性 掺tu 单药治疗多种her2靶向癌症. 与免疫疗法等其他抗癌疗法的联合试验也在进行中.
第一三共合作
第一三共公司, Limited (TSE: 4568) [referred to as 第一三共制药] and 澳门葡京网赌游戏 entered into a global collaboration to jointly develop and commercialise 掺tu (her2定向ADC) 2019年3月, 和datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in 2020年7月在日本，第一三共制药拥有专有权. 第一三共制药负责生产和供应 掺tu 和datopotamab deruxtecan.
澳门葡京网赌游戏在肿瘤学
澳门葡京网赌游戏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，澳门葡京网赌游戏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.
澳门葡京网赌游戏的愿景是重新定义癌症治疗和, 有一天,, 消除癌症作为死亡原因.
澳门葡京网赌游戏
澳门葡京网赌游戏(LSE/STO/Nasdaq: AZN)是一家全球性制药公司, 以科学为主导的澳门葡京赌博游戏公司，专注于发现, 发展, 以及肿瘤学处方药的商业化, 罕见疾病, 和澳门葡京赌博游戏, 包括心血管, 肾 & 新陈代谢和呼吸 & 免疫学. 总部设在剑桥, UK, 澳门葡京网赌游戏在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 澳门葡京网赌游戏.com 并在社交媒体上关注公司 @澳门葡京网赌游戏.
参考文献
1. ASCO. 乳腺癌. 可以在: http://www.Cancer.net/sites/Cancer.net/files/asco_answers_guide_breast.pdf. 2023年10月生效.
2. Iqbal N，等. 人表皮生长因子受体2 (HER2)在癌症中的过度表达及其治疗意义. Mol Biol Int. 2014; 852748.
3. 奥马尔·N，等. her2是一种新兴的非乳腺癌和非胃癌生物标志物. 发病机理. 2015;2(3):1-9.
4. Pillai R，等. 肺腺癌中的HER2突变:肺癌突变联盟的一份报告. 癌症. 2017;1;123(21): 4099-4105.
5. 国家癌症研究所. 掺tu标志着her2突变肺癌的首个靶向治疗. 可以在: http://www.Cancer.gov/news-events/Cancer-currents-blog/2022/fda-lung-Cancer-enhertu-her2. 2023年10月生效.
6. Siena S等. 人表皮生长因子受体2 (HER2)致癌基因在结直肠癌中的靶向作用. 安杂志. 2018 May; 29(5):1108-1119.
7. 闫敏，等. 不同癌症中HER2表达状态:对37,992例患者结果的回顾. 癌症转移. 2015年3月,34 (1):157 - 64.
8. Buza N等. Toward standard HER2 testing of 子宫内膜 serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice. 现代病理学. 2013年12月,26(12):1605 - 12所示.
9. meric - bernstein F等. 帕妥珠单抗联合曲妥珠单抗治疗her2扩增的转移性结直肠癌(MyPathway):来自多中心的最新报告, 非盲, 阶段2, 多篮研究. 《澳门葡京赌博游戏》杂志. 2019年4月;(4):518 - 530.