TOKYO & MUNICH & BASKING RIDGE, N.J.--(BUSINESS WIRE)--Initial results from the TROPION-Lung04 phase 1b trial showed that datopotamab deruxtecan (Dato-DXd) in combination with durvalumab, an anti-PD-L1 therapy, with or without carboplatin demonstrated encouraging responses and no new safety signals in patients with previously untreated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations.

TOKYO＆MUNICH＆BASKING RIDGE，N.J.-（BUSINESS WIRE）-TROPION-Lung04 1b期试验的初步结果显示，datopotamab deruxtecan（Dato-DXd）联合抗PD-L1治疗durvalumab，在没有可行的基因组改变的情况下，有或没有卡铂的患者在先前未治疗的晚期或转移性非小细胞肺癌（NSCLC）患者中表现出令人鼓舞的反应并且没有新的安全性信号。

These data were presented today during a late-breaking oral presentation (OA05.06) at the IASLC 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC23)..

这些数据今天在国际肺癌研究协会（#WCLC23）主办的IASLC 2023世界肺癌会议上进行了最新的口头报告（OA05.06）。。

Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/Nasdaq: AZN).

Datopotamab deruxtecan是由Daiichi Sankyo（TSE:4568）和AstraZeneca（LSE/STO/Nasdaq:AZN）共同开发的特异性工程TROP2定向DXd抗体-药物偶联物（ADC）。

More than one million people worldwide are diagnosed with advanced NSCLC each year.1,2 While first-line treatment with immune checkpoint inhibitors with or without chemotherapy has improved outcomes for patients with NSCLC without actionable genomic alterations, like EGFR or ALK, most patients eventually experience disease progression.3,4,5 TROP2 is a protein broadly expressed in a large majority of NSCLC tumors.6 There are currently no TROP2 directed ADCs approved for the treatment of patients with lung cancer.7,8.

全世界每年有超过100万人被诊断患有晚期非小细胞肺癌[1,2]。虽然一线治疗免疫检查点抑制剂联合或不联合化疗可改善NSCLC患者的预后，但无需可行的基因组改变，如EGFR或ALK，大多数患者最终会经历疾病进展.3,4,5 TROP2是一种在大多数NSCLC肿瘤中广泛表达的蛋白质.6目前还没有TROP2定向的ADC被批准用于治疗肺癌患者.7,8。

In previously untreated patients, datopotamab deruxtecan plus durvalumab (doublet; n=14) demonstrated an objective response rate (ORR) of 50.0% (95% confidence interval [CI]: 23.0-77.0), including seven partial responses (PR) and a disease control rate (DCR) of 92.9% (95% CI: 66.1-99.8). Response rates were higher in patients receiving datopotamab deruxtecan plus durvalumab and carboplatin (triplet; n=13) which demonstrated an ORR of 76.9% (95% CI: 46.2-95.0), including 10 PRs and a DCR of 92.3% (95% CI: 64.0-99.8).

在以前未经治疗的患者中，datopotamab deruxtecan加durvalumab（doublet；n=14）显示客观有效率（ORR）为50.0%（95%置信区间[CI]:23.0-77.0），包括7个部分反应（PR）和92.9%（95%CI:66.1-99.8）的疾病控制率（DCR）。接受datopotamab deruxtecan加durvalumab和卡铂（三联；n=13）的患者的反应率更高ORR为76.9%（95%CI:46.2-95.0），包括10个PR和92.3%的DCR（95%CI:64.0-99.8）。

Responses were observed across PD-L1 expression levels..

在PD-L1表达水平上观察到反应。。

“Most patients with advanced non-small cell lung cancer experience disease progression after initial treatment, underscoring the need for more effective first-line treatment options,” said Saiama Waqar, MD, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, and investigator in the trial.

华盛顿大学医学院西特曼癌症中心医学博士Saiama Waqar博士说：“大多数晚期非小细胞肺癌患者在初始治疗后会出现疾病进展，强调需要更有效的一线治疗方案。”密苏里州路易斯市，审判调查员。

“The TROPION-Lung04 results offer preliminary evidence for the efficacy of datopotamab deruxtecan in combination with durvalumab and chemotherapy in first-line advanced non-small cell lung cancer with no new safety signals. We eagerly await enrollment and results from the phase 3 program evaluating various datopotamab deruxtecan and immune checkpoint inhibitor combinations in this setting.”.

“TROPION-Lung04结果为datopotamab deruxtecan联合durvalumab和化疗治疗一线晚期非小细胞肺癌的疗效提供了初步证据，没有新的安全性信号。我们迫切期待着3期项目的入组和结果在这种情况下评估各种datopotamab deruxtecan和免疫检查点抑制剂组合“。

In both previously treated and untreated patients, the safety profiles of datopotamab deruxtecan and durvalumab with and without carboplatin were consistent with other clinical trials and with the known safety profile of each agent. Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred in 42.1% of patients receiving doublet therapy and 71.4% of patients receiving triplet therapy.

在先前治疗和未治疗的患者中，使用和不使用卡铂的datopotamab deruxtecan和durvalumab的安全性概况与其他临床试验和每种药物的已知安全性概况一致。接受双重治疗的患者中有42.1%发生3级或更高的治疗紧急不良事件（TEAE），接受三联治疗的患者中有71.4%发生了不良事件（TEAE）。

In patients receiving triplet therapy, the most common grade 3 or greater TEAEs (occurring in more than 15% of patients) were anemia (36%) and thrombocytopenia (21%). No grade 3 or higher TEAE occurred in more than 15% of patients receiving doublet therapy. Across treatment cohorts, there were four interstitial lung disease (ILD) events adjudicated as drug-related by an independent committee including one grade 1 event, two grade 2 events and one grade 4 event.

在接受三联疗法的患者中，最常见的3级或更高TEAE（发生率超过15%的患者）是贫血（36%）和血小板减少症（21%）。超过15%的接受双重治疗的患者没有发生3级或更高的TEAE。在整个治疗队列中，有四个间质性肺病（ILD）事件被独立委员会判定为与药物有关，包括一个1级事件，两个2级事件和一个4级事件。

No grade 5 ILD events were observed..

没有观察到5级ILD事件。。

“These early trial results further demonstrate the potential for datopotamab deruxtecan to enhance response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer and without actionable genomic alterations,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo.

“这些早期试验结果进一步证明了datopotamab deruxtecan在晚期非小细胞肺癌患者中增强对免疫检查点抑制剂的反应的潜力，并且没有可行的基因组改变，”肿瘤临床发展全球负责人Mark Rutstein博士说。，第一三共。

“We look forward to continuing to evaluate this promising TROP2 directed antibody drug conjugate in multiple ongoing phase 3 trials to address what has long been an unmet need for the lung cancer community across treatment settings.”.

“我们期待在多个正在进行的3期临床试验中继续评估这种有前景的TROP2定向抗体-药物偶联物，以解决肺癌社区在整个治疗环境中长期未满足的需求。”。

“Following the positive high-level results of TROPION-Lung01, these initial TROPION-Lung04 results in the first-line setting reinforce our confidence in datopotamab deruxtecan as a potential treatment option for patients with advanced non-small cell lung cancer,” said Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca.

“在TROPION-Lung01的阳性高水平结果之后，这些初始TROPION-Lung04在一线治疗中的结果增强了我们对datopotamab deruxtecan作为晚期非小细胞肺癌患者潜在治疗选择的信心，”阿斯利康首席医疗官兼肿瘤学首席开发官Cristian Massacesi说。

“Through our robust clinical program we are eager to continue evaluating this TROP2 directed antibody drug conjugate in lung cancer across treatment settings, alone and in novel combinations.”.

“通过我们强大的临床计划，我们渴望继续评估这种TROP2定向抗体-药物偶联物在肺癌治疗环境中的应用，无论是单独使用还是新型组合使用。”。

In the doublet cohort, 73.7% (n=14 of 19) of patients were previously untreated. In the triplet cohort, 92.9% (n=13 of 14) of patients were previously untreated. Both the doublet and triplet cohorts included patients with PD-L1 expression levels ranging from less than 1% (n=6, 6), 1% to 49% (n=6, 3) and 50% or greater (n=7, 5), respectively.

在双联队列中，73.7%（n=14/19）的患者以前未接受过治疗。在三联队列中，92.9%（n=13/14）的患者以前未接受过治疗。双联体和三联体队列均包括PD-L1表达水平低于1%（n=6,6），1%至49%（n=6,3）和50%或更高（n=7,5）。

As of the March 6, 2023 data cut-off, median study duration was six months for both cohorts and treatment was ongoing in 31.6% and 50.0% of patients in the doublet and triplet cohorts, respectively..

截至2023年3月6日的数据截止，两组患者的中位研究持续时间为6个月，双组和三组患者的治疗分别为31.6%和50.0%。。

Summary of TROPION-Lung04 Efficacy Results

TROPION-Lung04疗效结果总结

Responses in Previously Untreated Patients

以前未经治疗的患者的反应

Doublet Therapy (Cohort 2; n=14)

双联疗法（队列2；n=14）

Triplet Therapy (Cohort 4; n=13)

三联疗法（队列4；n=13）

ORR (confirmed and pending), %i (95% CI)

ORR（已确认和待定），%i（95%CI）

50.0% (23.0-77.0; n=7)

50.0%（23.0-77.0；n=7）

76.9% (46.2-95.0; n=10)

76.9%（46.2-95.0；n=10）

CR, %

CR，%

0%

0%

0%

0%

PR, %

公关，%

50.0% (n=7)

50.0%（n=7）

76.9% (n=10) ii

76.9%（n 10）ii

SD, %

SD，%

42.9% (n=6)

42.9%（n 6）

15.4% (n=2)

15.4%（n2）

PD, %

PD，%

7.1% (n=1)

7.1%（n=1）

7.7% (n=1)

7.7%（n=1）

DCR, % iii

DCR，%iii

92.9% (66.1-99.8; n=13)

92.9%（66.1-99.8；n=13）

92.3% (64.0-99.8; n=12)

92.3%（64.0-99.8；n=12）

CI, confidence interval; CR, complete response; DCR, disease control rate; ORR, objective response rate; PR, partial response; PD, progressive disease; SD, stable disease

CI，置信区间；CR，完全缓解；DCR，疾病控制率；ORR，客观回应率；公关，部分回应；PD，进行性疾病；SD，疾病稳定

i ORR is CR + PR

i ORR为CR+PR

ii One of the 10 partial responses in Cohort 4 was confirmed after data cut-off

ii队列4中10个部分反应中的一个在数据截止后得到确认

iiiDCR is best overall response of confirmed CR + confirmed PR + SD

iiiDCR是确认的CR+确认的PR+SD的最佳总体响应

Daiichi Sankyo and AstraZeneca have three phase 3 trials evaluating datopotamab deruxtecan-based combinations as potential first-line treatment options for patients with advanced or metastatic NSCLC without actionable genomic alterations compared to the respective standard of care for the patient population of each study.

Daiichi-Sankyo和AstraZeneca有三项三期临床试验评估基于datopotamab-deruxtecan的组合作为晚期或转移性NSCLC患者的潜在一线治疗选择，与每项研究的患者群体的相应护理标准相比，没有可行的基因组改变。

TROPION-Lung07 is evaluating datopotamab deruxtecan plus pembrolizumab with or without chemotherapy in patients with non-squamous disease and PD-L1 expression less than 50%. TROPION-Lung08 is evaluating datopotamab deruxtecan plus pembrolizumab in patients with PD-L1 expression of 50% or greater. AVANZAR is evaluating datopotamab deruxtecan plus durvalumab and carboplatin in patients regardless of PD-L1 expression or tumor histology..

TROPION-Lung07正在评估datopotamab deruxtecan加pembrolizumab联合或不联合化疗治疗非鳞状细胞病和PD-L1表达低于50%的患者。TROPION-Lung08正在评估datopotamab deruxtecan加pembrolizumab治疗PD-L1表达50%或更高的患者。无论PD-L1表达或肿瘤组织学如何，AVANZAR都在评估datopotamab deruxtecan加durvalumab和卡铂治疗患者。。

About TROPION-Lung04

关于TROPION-Lung04

TROPION-Lung04 is an ongoing global, open-label, 11-cohort phase 1b trial evaluating the efficacy and safety of datopotamab deruxtecan (4 mg/kg or 6 mg/kg) in combination with immunotherapy (durvalumab, AZD2936 or MEDI5752) with or without up to four cycles of carboplatin in patients with advanced or metastatic NSCLC without actionable genomic alterations.

TROPION-Lung04是一项正在进行的全球性，开放标签的11队列1b期临床试验，评估datopotamab deruxtecan（4 mg/kg或6 mg/kg）联合免疫治疗（durvalumab，AZD2936或MEDI5752）的疗效和安全性。在没有可行的基因组改变的晚期或转移性NSCLC患者中，多达四个周期的卡铂。

Patients enrolled in the cohorts evaluating durvalumab were previously untreated or had received one or fewer lines of systemic chemotherapy without concomitant immunotherapy. The primary endpoints of TROPION-Lung04 are safety and tolerability. Secondary endpoints include ORR, DCR, duration of response and progression-free survival as assessed by investigator.

参加评估durvalumab队列的患者以前未接受过治疗，或接受过一次或多次全身化疗，未伴随免疫治疗。TROPION-Lung04的主要终点是安全性和耐受性。次要终点包括ORR，DCR，反应持续时间和研究者评估的无进展生存期。

TROPION-Lung04 will enroll approximately 230 patients globally..

TROPION-Lung04将在全球招募约230名患者。。

About Non-Small Cell Lung Cancer

关于非小细胞肺癌

More than one million people worldwide are diagnosed with advanced NSCLC each year.1,2 While targeted therapies and immune checkpoint inhibitors have improved patient outcomes, advanced NSCLC has a poor prognosis and is associated with worsening outcomes after each line of subsequent therapy.3,4,5

全世界每年有超过100万人被诊断患有晚期非小细胞肺癌[1,2]。虽然靶向治疗和免疫检查点抑制剂改善了患者预后，但晚期非小细胞肺癌预后不良，并且在随后的每一系列治疗后预后恶化.3,4,5

Most patients with NSCLC have tumors that do not express a known actionable genomic alteration (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET or MET).9,10,11 The current first-line standard of care for these patients is immune checkpoint inhibitors with or without platinum-based chemotherapy. Approximately 40% to 60% of tumors will not respond to this initial treatment and while these therapies may improve survival for patients whose tumors do respond, most will experience disease progression.5,7.

大多数NSCLC患者的肿瘤不表达已知的可行基因组改变（如EGFR，ALK，ROS1，NTRK，BRAF，RET或MET）[9,10,11]。目前这些患者的一线护理标准是免疫检查点抑制剂，有或没有铂类化疗。大约40%至60%的肿瘤对这种初始治疗没有反应，虽然这些疗法可以提高肿瘤确实有反应的患者的生存率，但大多数会经历疾病进展。

TROP2, a transmembrane glycoprotein, is broadly expressed in a large majority of NSCLC tumors.6 There are currently no TROP2 directed ADCs approved for the treatment of lung cancer.

TROP2是一种跨膜糖蛋白，在绝大多数NSCLC肿瘤中广泛表达.6目前还没有TROP2定向的ADC被批准用于治疗肺癌。

About the Daiichi Sankyo and AstraZeneca Collaboration

关于第一三共和阿斯利康的合作

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan..

Daiichi-Sankyo和AstraZeneca于2019年3月与ENHERTU和2020年7月的datopotamab deruxtecan进行了全球合作，共同开发和商业化，但日本Daiichi-Sankyo拥有每个ADC的专有权。第一三共负责ENHERTU和datopotamab deruxtecan的制造和供应。。

About Datopotamab Deruxtecan (Dato-DXd)

关于Datopotamab Deruxtecan（Dato DXd）

Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of the lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform.

Datopotamab deruxtecan（Dato-DXd）是一种研究性TROP2定向ADC。datopotamab deruxtecan采用第一三共专有的DXd ADC技术设计，是第一三共肿瘤学管道中的领先ADC之一，也是阿斯利康ADC科学平台上最先进的项目之一。

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) via tetrapeptide-based cleavable linkers..

Datopotamab deruxtecan由与札幌医科大学合作开发的人源化抗TROP2 IgG1单克隆抗体组成，通过基于四肽的可切割接头连接到许多拓扑异构酶I抑制剂有效载荷（exatecan衍生物，DXd）。。

A comprehensive development program called TROPION is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple tumors, including NSCLC, triple negative breast cancer and hormone receptor positive, HER2 negative breast cancer. Beyond the TROPION program, datopotamab deruxtecan also is being evaluated in novel combinations in several ongoing trials..

一项名为TROPION的综合开发计划正在全球范围内进行，超过12项试验评估了datopotamab deruxtecan在多种肿瘤中的疗效和安全性，包括NSCLC，三阴性乳腺癌和激素受体阳性，HER2阴性乳腺癌。除了TROPION计划之外，datopotamab deruxtecan还在几个正在进行的试验中以新颖的组合进行评估。。

In NSCLC, the TROPION-Lung07, TROPION-Lung08 and AVANZAR phase 3 trials are evaluating datopotamab deruxtecan and immune checkpoint inhibitor combinations as potential first-line treatment options for patients with advanced or metastatic disease, a strategy informed by the results of two early trials.

在NSCLC中，TROPION-Lung07，TROPION-Lung08和AVANZAR 3期临床试验正在评估datopotamab deruxtecan和免疫检查点抑制剂组合作为晚期或转移性疾病患者的潜在一线治疗选择，这一策略由两项早期试验。

AstraZeneca is also researching a potential diagnostic test to help identify patients most likely to benefit from treatment with datopotamab deruxtecan..

阿斯利康还在研究一种潜在的诊断测试，以帮助确定最有可能从datopotamab deruxtecan治疗中获益的患者。。

About the DXd ADC Portfolio of Daiichi Sankyo

关于第一三共的DXd ADC产品组合

The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Four additional Daiichi Sankyo DXd ADCs include patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd; DS-7300), a B7-H3 directed ADC, raludotatug deruxtecan (R-DXd; DS-6000), a CDH6 directed ADC, and DS-3939, a TA-MUC1 directed ADC..

第一三共的DXd ADC产品组合目前由六种ADC组成，用于多种类型癌症的临床开发。HER2定向ADC ENHERTU和TROP2定向ADC datopotamab deruxtecan（Dato-DXd）正在与AstraZeneca共同开发和商业化。另外四个Daiichi Sankyo DXd ADC包括patritumab deruxtecan（HER3 DXd），HER3定向ADC，ifinatamab deruxtecan（I-DXd；DS-7300），B7-H3定向ADC，raludotatug deruxtecan（R-DXd；DS-6000）），CDH6定向ADC和DS-3939，TA-MUC1定向ADC。。

Designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers..

使用Daiichi Sankyo专有的DXd ADC技术设计，在表达特定细胞表面抗原的癌细胞内靶向并递送细胞毒性有效载荷，每个ADC由与许多拓扑异构酶I抑制剂有效载荷（exatecan衍生物，DXd）连接的单克隆抗体组成。基于四肽的可切割接头。。

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

Datopotamab deruxtecan，ifinatamab deruxtecan，patritumab deruxtecan，raludotatug deruxtecan和DS-3939是尚未在任何国家批准用于任何适应症的研究药物。安全性和有效性尚未确定。

About Daiichi Sankyo

关于第一三共

Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need.

第一三共是一家创新的全球医疗保健公司，为社会的可持续发展做出贡献，发现，发展和提供新的护理标准，以丰富世界各地的生活质量。凭借120多年的经验，第一三共利用其世界一流的科学技术为癌症，心血管疾病和其他医疗需求未得到满足的疾病患者创造新的模式和创新药物。

For more information, please visit www.daiichisankyo.com..

欲了解更多信息，请访问www.daiichisankyo.com。。

References

工具书类

1 Siegel R, et al. CA Cancer J Clin. 2021;71:7-33.

Siegel R等人，CA癌症J临床。2021年；71:7-33。

2 World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Accessed September 2023.

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