澳门葡京网赌游戏和第一三共制药的datopotamab deruxtecan降低了风险
疾病进展或死亡的风险降低25%
在非鳞状肿瘤患者中，这一比例为37%
Datopotamab deruxtecan是第一个抗体药物偶联物，在这种高未满足需求的情况下，与多西他赛相比，在统计学上显着改善PFS
关键TROPION-Lung01 III期试验的阳性结果显示，与多西紫杉醇相比，datopotamab deruxtecan (Dato-DXd)在无进展生存期(PFS)的主要终点方面表现出统计学上显著的改善, 目前的护理标准, 局部晚期或转移性非小细胞肺癌(NSCLC)患者既往至少接受过一种治疗.
今天，在马德里举行的欧洲肿瘤医学学会(ESMO) 2023年大会主席研讨会上，这些数据将在datopotamab deruxtecan的两次最新报告中的第二次报告中分享, 西班牙(LBA12).
Datopotamab deruxtecan是澳门葡京网赌游戏(AstraZeneca)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).
Datopotamab deruxtecan reduced the risk of disease progression or death by 25% compared to docetaxel (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.62-0.91; p=0.004)，由盲法独立中心评价(BICR)评估。. 中位PFS为4.datopotamab deruxtecan治疗的患者为4个月，而非3个月.多西紫杉醇7例. 结果还显示确定的客观缓解率(ORR)为26.4%的患者接受datopotamab deruxtecan治疗，而ORR为12.8%用多西紫杉醇.
非鳞状NSCLC患者, Datopotamab deruxtecan显示出有临床意义的益处, reducing the risk of disease progression or death by 37% compared to docetaxel (HR 0.63; 95% CI 0.51-0.78) BICR评估. 中位PFS为5.datopotamab deruxtecan治疗的患者为6个月，而非3个月.多西紫杉醇7例. 确认ORR为31.2% was observed with datopotamab deruxtecan, including four complete responses (CRs), versus 12.8%的多西紫杉醇组无cr. Datopotamab deruxtecan did not demonstrate a PFS benefit in patients with squamous NSCLC.
对于总生存期(OS)的双重主要终点, interim results numerically favoured datopotamab deruxtecan over docetaxel in the overall population (HR 0.90; 95% CI 0.72-1.13)和非鳞状肿瘤患者(HR 0.77 95% CI: 0.59-1.01), however, results did not reach statistical significance at the time of this data cut-off. 试验正在进行中，操作系统将在最终分析中进行评估.
亚伦Lisberg, MD, UCLA Health, 胸内科肿瘤学研究人员, 他说:“对于晚期非小细胞肺癌患者, current standard of care second-line docetaxel is associated with limited benefit and substantial toxicity. datopotamab deruxtecan观察到无进展生存期的改善, 尤其是在非鳞状肿瘤患者中, and the improved tolerability of this antibody drug conjugate compared to docetaxel, 对肺癌患者来说是一个有意义的进步."
Susan Galbraith，肿瘤学研究中心执行副总裁&D, AstraZeneca, Datopotamab deruxtecan是澳门葡京赌博游戏未来设想的抗体药物偶联物改善并最终取代根深蒂固的护理标准的核心, 像化疗, 在多种癌症类型中. TROPION-Lung01的研究结果首次证明，在晚期非小细胞肺癌患者中，抗体药物偶联物可以比传统化疗延迟疾病进展或死亡的时间更长. 考虑到datopotamab deruxtecan与化疗相比，治疗相关严重不良事件的负担更低，这一点尤其值得注意.”
Ken Takeshita，医学博士，全球主管，R&D, 第一三共制药, said, datopotamab deruxtecan两项关键试验中的第二项在ESMO上显示的结果进一步支持了澳门葡京赌博游戏的DXd抗体药物偶联技术在不同靶点和癌症类型上改变实践的潜力. The benefit seen in patients with non-squamous tumours is particularly impressive and, 结合TROPION-Lung05的数据, 提供了有希望的证据，表明datopotamab deruxtecan可能在治疗非小细胞肺癌患者中发挥重要作用，这些患者目前在初始治疗后的有效选择有限.”
In the TROPION-Lung01 trial, no new safety concerns were identified with datopotamab deruxtecan. datopotamab deruxtecan的中位治疗时间为4.2 versus 2.多西紫杉醇8个月. 在datopotamab deruxtecan组和docetaxel组中，分别有25%和41%的患者发生了3级或更高级别的治疗相关不良事件(TRAEs), 分别. 最常见的3级及以上trae是中性粒细胞减少症(1%), 23%), 口腔炎(6%, 1%), anaemia (4%, 4%), 衰弱(3%, 2%), nausea (2%, 1%)和疲劳(1%), 2%).
3级或更高级别的药物相关间质性肺疾病(ILD)事件发生在3%和1%的datopotamab deruxtecan和docetaxel组患者中, 分别. 在datopotamab derxtecan臂, there were seven Grade 5 ILD events (2%) adjudicated as drug-related by an independent committee. The primary cause of death in four of these cases was attributed to disease progression by the treating investigator. 在7个已裁定的5级ILD项目中，有4个(1.(7%)在非鳞状NSCLC患者中.6%)在鳞状NSCLC患者中. 在多西紫杉醇组中，1例与药物相关的5级ILD事件(0.05).3%)发生.
根据肿瘤组织学入组的患者在治疗组中是一致的，真实世界的发病率在数据不达单德鲁德康组和多西他赛组中分别为78%和77%, 分别, 有非鳞状肿瘤的.1 双臂相连, 17%的患者肿瘤表达可操作的基因组改变, 如表皮生长因子受体(EGFR)突变. 截至2023年3月29日数据截止日期, 52 patients remained on treatment with datopotamab deruxtecan and 17 remained on docetaxel.
TROPION-Lung01疗效总结
总体试验人群 |
||
|---|---|---|
|
Datopotamab deruxtecan (n=299) |
多西他赛(n = 305) |
中位PFS (95% CI) i |
4.4 months (4.2-5.6) |
3.7 months (2.9-4.2) |
HR (95% CI) |
0.75 (0.62-0.91) |
|
p-value ii |
p=0.004 |
|
中位OS (95% CI) iii |
12.四个月(10).8-14.8) |
11.0 months (9.8-12.5) |
HR (95% CI) |
0.90 (0.72-1.13) |
|
ORR，确认(95% CI) i,iv |
26.4% (21.5-31.8) |
12.8% (9.3-17.1) |
CR rate |
1.3% |
0% |
PR rate |
25.1% |
12.8% |
中位DoR (95% CI) i |
7.1 months (5.6-10.9) |
5.6 months (5.4-8.1) |
Non-squamous组织学 |
||
|
Datopotamab deruxtecan (n=229) |
多西他赛(n = 232) |
中位PFS (95% CI) i |
5.6 months (4.4-7.0) |
3.7 months (2.9-4.2) |
HR (95% CI) |
0.63 (0.51-0.78) |
|
OS hr (95% ci) iii |
0.77 (0.59-1.01) |
|
奥尔,确认 i,iv |
31.2% |
12.8% |
Median DoR i |
7.7 months |
5.6 months |
鳞状组织学 |
||
|
Datopotamab deruxtecan (n=70) |
多西他赛(n = 73) |
中位PFS (95% CI) i |
2.8 months (1.9-4.0) |
3.9 months (2.8-4.5) |
HR (95% CI) |
1.38 (0.94-2.02) |
|
OS hr (95% ci) iii |
1.32 (0.87-2.00) |
|
奥尔,确认 i,iv |
9.2% |
12.7% |
Median DoR i |
5.9 months |
8.1 months |
CI, confidence interval; CR, complete response; DoR, duration of response; HR, hazard ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, 部分响应
i 经BICR评估
ii p值预设边界为0.008
iii 中位随访时间为11.8 and 11.7 months for the datopotamab deruxtecan and docetaxel arms, 分别, OS data were not mature
iv ORR为(完全响应+部分响应)
TROPION-Lung05结果
TROPION-Lung05 II期试验的初步结果显示，datopotamab deruxtecan对重度预处理的局部晚期或转移性NSCLC患者显示出令人鼓舞的抗肿瘤活性，这些患者具有可操作的基因组改变，包括那些具有EGFR突变和间变性淋巴瘤激酶(ALK)重排的患者. These data were presented at the ESMO 2023 Congress on Saturday, 21 October (1314MO).
In the overall population (n=137), datopotamab deruxtecan demonstrated a confirmed ORR of 35.8%, including four CRs and 45 部分响应s, and a disease control rate (DCR) of 78.8%. 中位PFS为5.4 months. EGFR突变患者(n=78), 最大的子群, datopotamab deruxtecan的ORR为43.6%， DCR为82.1%.
最常见的3级及以上trae是口炎(10%)。, 贫血(6%), 食欲下降(4%)和疲劳(4%). There were five ILD events (4%) adjudicated as drug-related by an independent committee, 包括四个一、二级项目和一个五级项目.
Notes
非小细胞肺癌
全世界每年有超过100万人被诊断为晚期非小细胞肺癌.2,3 Approximately 30% and 70% of NSCLC tumours are of squamous or non-squamous histology, 分别, 后者包括腺癌和大细胞癌.1 While immunotherapy and targeted therapies have improved outcomes in the first-line setting, 大多数患者最终经历疾病进展并接受化疗.4-6 For decades, 化疗是晚期非小细胞肺癌患者在没有其他治疗选择的情况下的最后一种治疗方法，尽管疗效有限，而且已知有副作用.4-6
TROP2, a transmembrane glycoprotein, is broadly expressed in a large majority of NSCLC tumours.7 There are currently no TROP2-directed ADCs approved for the treatment of lung cancer.8,9
TROPION-Lung01
TROPION-Lung01是一种正在进行的全球性药物, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) vs多西他赛(75 mg/m)2局部晚期或转移性NSCLC患者有或没有可操作的基因组改变，先前至少接受过一种治疗. 具有可操作的基因组改变的患者以前接受过基于铂的化疗和批准的靶向治疗. 没有已知可操作的基因组改变的患者先前接受过治疗, 并发或顺序, 铂基化疗和PD-1或PD-L1抑制剂.
TROPION-Lung01的双重主要终点是通过BICR和OS评估的PFS. 关键次要终点包括研究者评估的PFS, ORR, DoR, 响应时间, DCR由BICR和研究者共同评估, and safety.
TROPION-Lung01在亚洲招募了约600名患者, Europe, 北美和南美. 欲知详情，请浏览 临床试验.gov.
TROPION-Lung05
TROPION-Lung05是一个持续的全球, multicenter, single-arm, open-label Phase II study evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg)，适用于在至少一种酪氨酸激酶抑制剂和至少一种铂基化疗方案(伴或不伴其他全身治疗)上或之后，有可操作基因组改变且疾病进展的局部晚期或转移性NSCLC患者。. 有包括EGFR在内的一种或多种基因组改变的患者, ALK, ROS1, NTRK, BRAF, RET, or MET and who received up to four prior lines of treatment were eligible for the study.
主要试验终点是由BICR评估的ORR. 次要疗效终点包括DOR, 可测量肿瘤直径总和的最佳百分比变化, DCR, 临床获益率, PFS, 响应时间和操作系统. Safety endpoints include treatment emergent adverse events and other safety parameters. TROPION-Lung05在全球招募了137名患者. 欲知详情，请浏览 临床试验.gov.
Dato-DXd (Dato-DXd)
Dato-DXd (Dato-DXd)是一种实验性TROP2定向ADC. 采用第一三共制药专有的DXd ADC技术设计, datopotamab deruxtecan is one of six ADCs in the oncology pipeline of 第一三共制药, 也是澳门葡京网赌游戏ADC科学平台中最先进的项目之一. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, 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.
一项名为TROPION的综合开发计划正在全球范围内进行，超过12项试验评估datopotamab deruxtecan治疗多种肿瘤的疗效和安全性, 包括非小细胞肺癌, 三阴性乳腺癌和HR阳性, HER2低或阴性乳腺癌. 在TROPION项目之外, datopotamab deruxtecan also is being evaluated in novel combinations in several ongoing trials. 澳门葡京网赌游戏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.
第一三共合作
AstraZeneca and 第一三共制药 entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 和datopotamab deruxtecan July 2020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.
澳门葡京网赌游戏治疗肺癌
澳门葡京网赌游戏正致力于通过早期疾病的检测和治疗，使肺癌患者更接近治愈, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. 通过定义新的治疗靶点和研究创新方法, 公司的目标是将药物匹配到最能受益的患者.
The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib)和 Iressa (吉非替尼); Imfinzi (durvalumab)和 Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) 和datopotamab deruxtecan collaboration with 第一三共制药; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.
澳门葡京网赌游戏是Lung Ambition Alliance的创始成员之一, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, 包括治疗之外的.
澳门葡京网赌游戏在肿瘤学
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, 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. 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.
澳门葡京网赌游戏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.
AstraZeneca
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, development, 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, Renal & 新陈代谢和呼吸 & Immunology. 总部设在剑桥, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit xal666.com 并在社交媒体上关注公司 @AstraZeneca.
Contacts
References
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2. Siegel R，等. 癌症统计，2021年. 癌症J临床. 2021;71:7-33.
3. 世界卫生组织. 国际癌症研究机构. 肺部情况说明. 可以在: http://efaidnbmnnnibpcajpcglclefindmkaj/http://gco.iarc.fr /今天/数据/资料/癌症/ 15-Lung-fact-sheet.pdf. 2023年10月生效.
4. 陈锐，等. 晚期非小细胞肺癌的新兴治疗药物. [J]血液学. 2020;13(1):58.
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6. 皮尔彻，A，等. Docetaxel in the Treatment of Non-small Cell Lung Cancer (NSCLC) – An Observational Study Focusing on Symptom Improvement. 抗癌的研究. 2013;33(9):3831-3836.
7. Mito R, et al. Clinical impact of TROP2 in non‐small lung cancers and its correlation with abnormal p53 nuclear accumulation. Pathol Int. 2020;70(5):287-294.
8. Rodríguez-Abreau D等. 培美曲塞加铂联合或不联合派姆单抗治疗先前未治疗的转移性非鳞状NSCLC患者:KEYNOTE-189协议指定的最终分析. Ann Onc. [j]; 2011;32(7): 881-895.
9. 美国癌症协会. 非小细胞肺癌的靶向药物治疗. 可以在: http://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html. 2023年5月.