Enhertu demonstrated clinically meaningful survival across multiple HER2-expressing advanced solid tumours in DESTINY-PanTumor02 Phase II trial

全球十大赌博靠谱平台和第一三共的Enhertu显示中位无进展
survival of 6.9 months and median overall survival of 13.4 months in the overall
trial population

结果重申了Enhertu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
discussions with global regulatory authorities
 

正在进行的DESTINY-PanTumor02 II期试验初步分析的阳性结果表明 Enhertu 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.

These results, 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), Spain and simultaneously published in the Journal of Clinical Oncology.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. 

In the primary analysis, Enhertu demonstrated a median PFS of 6.9 months (95% confidence interval [CI] 5.6-8.0) and a median OS of 13.4 months (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, including either biliary tract, bladder, cervical, endometrial, ovarian, pancreatic cancers or other tumours, as assessed by investigator. Enhertu also continued to show a confirmed objective response rate (ORR) of 37.1% and a median duration of response (DoR) of 11.3 months (95% CI 9.6-17.8) in these patients.

Funda 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, US and principal investigator for the trial, 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. Based on these results, Enhertu has the potential to change the course of disease for certain patients with HER2-expressing advanced cancers who have limited treatment options and currently no approved HER2-directed therapies.”

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, 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. Enhertu has the potential to offer 改善了先前接受过her2表达癌症治疗的特定患者的预后, 推荐全球最大网赌正规平台希望能尽快将这种重要的药物带给患者.”

Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo, said: “Improving survival outcomes for patients is one of the primary goals of cancer treatment and the clinically meaningful progression-free and overall survival results seen in DESTINY-PanTumor02 are encouraging. These results provide additional evidence for Enhertu to potentially become the first antibody drug conjugate approved in a tumour-agnostic setting in patients whose tumours express HER2.”

Summary of results: DESTINY-PanTumor02 primary analysis

BTC, biliary tract cancer; CI, confidence interval; DoR, duration of response; IHC, immunohistochemistry; NR, not reached; ORR, objective response rate; OS, overall survival; PFS, progression-free survival
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 IHC 3+ (n=75) or 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 IHC 3+ (n=46) or IHC 2+ (n=34) status.
ⁱResponses in extramammary Paget disease, head and neck cancer, oropharyngeal neoplasm, and salivary gland cancer.

At the primary analysis of the DESTINY-PanTumor02 trial, 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, where Enhertu demonstrated a confirmed ORR of 61.3% (95% CI: 49.4-72.4) as part of an exploratory analysis. Enhertu demonstrated a median PFS of 11.9 months (95% CI: 8.2-13.0) and a median OS of 21.1 months (95% CI: 15.3-29.6) in patients with IHC 3+ tumour expression, with a median DoR of 22.1 months (95% CI: 9.6-NR) achieved in this patient population. 这些具有临床意义的结果强化了该试验中期分析的结果 presented 在今年早些时候的2023年美国临床肿瘤学会年会上.

The safety profile of Enhertu 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%), anaemia (10.9%), fatigue (7.1%) and thrombocytopenia (5.6%).

In DESTINY-PanTumor02, 28 patients (10.5%)发生间质性肺疾病(ILD)或与治疗相关的肺炎 Enhertu as determined by an independent adjudication committee. The majority (9.0%) were low-grade (Grade 1 or 2) with one (0.4%) Grade 3 event, no Grade 4 events and three (1.1%) Grade 5 events observed.

Notes

HER2 expression in solid tumours
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

While HER2-directed therapies have been used to treat breast, gastric, lung and colorectal cancers, 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, bladder, cervical, endometrial, ovarian and pancreatic cancers.³ 在这些额外的肿瘤类型中不常规进行检测，因此, available literature is limited. 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 there are currently no approved HER2-directed therapies for these cancers.^2,9

DESTINY-PanTumor02
DESTINY-PanTumor02 is a global, multicentre, multi-cohort, open-label Phase II trial evaluating the efficacy and safety of Enhertu (5.4mg/kg)用于治疗先前治疗过的表达her2的肿瘤, including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer or other tumours.

DESTINY-PanTumor02的主要疗效终点是研究者评估的确认ORR. Secondary endpoints include DoR, disease control rate, PFS, OS, safety, tolerability and pharmacokinetics.

DESTINY-PanTumor02已经在亚洲、欧洲和北美的多个地点招募了267名患者. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu 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, (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4mg/kg) is approved in more than 55 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer 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.

Enhertu (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 IHC 2+/in-situ hybridisation [ISH]-) breast cancer 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.

Enhertu (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 cancer whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally-approved test, 并且根据DESTINY-Lung02试验的结果接受了先前的全身治疗. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric 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.

Enhertu development programme
A comprehensive clinical development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. 与免疫疗法等其他抗癌疗法的联合试验也在进行中.

Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in oncology
全球十大赌博靠谱平台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, 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，全球十大赌博靠谱平台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.

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, 全球十大赌博靠谱平台在100多个国家开展业务，其创新药物被全球数百万患者使用. Please visit um1515.net and follow the Company on Social Media @AstraZeneca.

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