TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--The first patients have been dosed in three global, randomized phase 3 trials evaluating the efficacy and safety of datopotamab deruxtecan (Dato-DXd)-based combinations in patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC)..

东京和新泽西州巴斯金岭（BUSINESS WIRE）--首批患者已在三项全球随机3期临床试验中服用，这些试验评估了基于达托单抗-德鲁替康（Dato-DXd）的联合用药对局部晚期或转移性非鳞状非小细胞肺癌（NSCLC）患者的疗效和安全性。。

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

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

TROPION-Lung10 is evaluating datopotamab deruxtecan plus rilvegostomig, AstraZeneca’s PD-1/TIGIT bispecific antibody, or rilvegostomig alone versus pembrolizumab in patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with high PD-L1 expression (tumor cells [TC] ≥ 50%) and without actionable genomic alterations..

TROPION-Lung10正在评估达托单抗-德鲁替康联合利维格司他米、阿斯利康的PD-1/TIGIT双特异性抗体或单独使用利维格司他米与派姆单抗治疗先前未经治疗的局部晚期或转移性非鳞状细胞癌患者的PD-L1高表达（肿瘤细胞[TC]≥50%）且无可行的基因组改变。。

TROPION-Lung14 is evaluating datopotamab deruxtecan plus osimertinib, AstraZeneca’s EGFR tyrosine kinase inhibitor (TKI), versus osimertinib alone in patients with previously untreated locally advanced or metastatic EGFR mutated nonsquamous NSCLC.

TROPION-Lung14正在评估达托单抗联合奥西替尼（阿斯利康的EGFR酪氨酸激酶抑制剂（TKI））与单独使用奥西替尼治疗先前未经治疗的局部晚期或转移性EGFR突变的非鳞状细胞癌患者。

TROPION-Lung15 is evaluating datopotamab deruxtecan with or without osimertinib versus platinum-based doublet chemotherapy in patients with locally advanced or metastatic nonsquamous EGFR mutated NSCLC whose disease progressed on prior treatment with osimertinib.

TROPION-Lung15正在评估达托单抗-德鲁替康联合或不联合osimertinib与铂类双联化疗治疗局部晚期或转移性非鳞癌EGFR突变NSCLC患者，其疾病在先前接受osimertinib治疗后进展。

“These three trials in either high PD-L1 expressing or EGFR mutated nonsquamous non-small cell lung cancer are critical to helping us understand the potential role of datopotamab deruxtecan in treating patients across different lines and types of lung cancer,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo.

“这三项针对高PD-L1表达或EGFR突变的非鳞状非小细胞肺癌的试验对于帮助我们了解达托帕单抗deruxtecan在治疗不同类型肺癌患者中的潜在作用至关重要，”第一三共肿瘤临床开发全球负责人马克·鲁斯坦（Mark Rutstein）医学博士说。

“Our growing TROPION clinical program, which now consists of seven phase 3 trials demonstrates our commitment to understanding the full potential of datopotamab deruxtecan in lung cancer.”.

“我们不断增长的TROPION临床计划，现在由七项3期临床试验组成，证明了我们致力于了解达托巴单抗deruxtecan在肺癌中的全部潜力。”。

“Clinical research suggests that combining an antibody drug conjugate with a targeted treatment or a bispecific immunotherapy may drive stronger and more durable tumor responses in patients with a variety of cancers including lung cancer,” said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca.

阿斯利康首席医学官兼肿瘤学首席开发官克里斯蒂安·马萨西（Cristian Massacesi）医学博士说：“临床研究表明，将抗体-药物偶联物与靶向治疗或双特异性免疫疗法相结合，可能会对包括肺癌在内的多种癌症患者产生更强，更持久的肿瘤反应。”。

“The initiation of these additional three phase 3 trials of datopotamab deruxtecan in combination with our agents, osimertinib and rilvegostomig illustrates our commitment to exploring potential synergies within our oncology pipeline as well as the full potential and combinability of this TROP2 directed antibody drug conjugate across multiple segments and settings of non-small cell lung cancer.”.

“达托单抗-德鲁替康联合我们的药物osimertinib和rilvegostomig启动了这些额外的三期临床试验，这表明我们致力于探索我们肿瘤学管道内的潜在协同作用，以及这种TROP2定向抗体-药物缀合物在多个节段和非小细胞肺癌环境中的全部潜力和可组合性。”。

About TROPION-Lung10

关于TROPION-Lung10

TROPION-Lung10 is a global, multicenter, open-label, three-arm phase 3 trial where patients will be randomized in a 2:1:2 ratio to evaluate the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) in combination with rilvegostomig (750 mg) or rilvegostomig (750 mg) monotherapy versus pembrolizumab (200 mg) monotherapy in adult patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations..

TROPION-Lung10是一项全球性，多中心，开放标签的三臂3期临床试验，患者将以2:1:2的比例随机分组，以评估达托单抗deruxtecan（6.0 mg/kg）联合rilvegostomig（750 mg）或rilvegostomig（750 mg）单药治疗与pembrolizumab（200 mg）单药治疗先前未经治疗的PD-L1高表达（TC≥50%）且无可行基因组改变的局部晚期或转移性非鳞状非小细胞肺癌的成年患者的疗效和安全性。。

The dual primary endpoints of TROPION-Lung10 are progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS) in patients with TROP2 positive tumors receiving datopotamab deruxtecan in combination with rilvegostomig versus the pembrolizumab arm. A pre-specified retrospective analysis from tumor biopsies collected pretreatment will be conducted following validation of a potential TROP2 biomarker determined by quantitative continuous scoring, a computational pathology approach..

TROPION-Lung10的双重主要终点是无进展生存期（PFS），通过盲法独立中央评估（BICR）和总生存期（OS）评估TROP2阳性肿瘤患者接受达托单抗-德鲁替康联合利维格司米格与pembrolizumab臂。。。

Key secondary endpoints for all arms of the trial include PFS as assessed by BICR and investigator and OS in the intention-to-treat (ITT) population, objective response rate (ORR) as assessed by BICR and duration of response (DoR) as assessed by BICR and investigator in both TROP2 biomarker positive and the ITT populations.

所有试验组的关键次要终点包括BICR和研究者评估的PFS以及意向治疗（ITT）人群中的OS，BICR评估的客观缓解率（ORR）和BICR和研究者评估的TROP2生物标志物阳性和ITT人群的缓解持续时间（DoR）。

The safety and tolerability of datopotamab deruxtecan in combination with rilvegostomig and rilvegostomig monotherapy as compared with pembrolizumab also will be assessed..

与pembrolizumab相比，datopotamab deruxtecan联合rilvegostomig和rilvegostomig单药治疗的安全性和耐受性也将进行评估。。

TROPION-Lung10 will enroll approximately 675 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov.

TROPION-Lung10将在亚洲，欧洲，北美，大洋洲和南美招募约675名患者。有关更多信息，请访问ClinicalTrials.gov。

The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd. (Nasdaq/TASE: CGEN).

rilvegostomig的TIGIT成分来源于Compugen Ltd.（纳斯达克/塔斯社：CGEN）开发的临床阶段抗TIGIT抗体COM902。

About TROPION-Lung14

关于TROPION-Lung14

TROPION-Lung14 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) in combination with osimertinib (80 mg) versus osimertinib (80 mg) monotherapy in adult patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with an EGFR mutation (Exon 19 deletion and/or L858R).

TROPION-Lung14是一项全球性，随机，多中心，开放标签的3期临床试验，评估达托巴单抗（6.0 mg/kg）联合osimertinib（80 mg）与osimertinib（80 mg）单药治疗成人患者的疗效和安全性。先前未经治疗的局部晚期或转移性非鳞状细胞癌伴EGFR突变（外显子19缺失和/或L858R）。

The randomized period of the trial is preceded by a single-arm safety run-in period which will enroll approximately 20 patients to evaluate the combination therapy..

试验的随机期之前是单臂安全磨合期，将招募大约20名患者评估联合治疗。。

The primary endpoint of TROPION-Lung14 is PFS as assessed by BICR. Key secondary endpoints include central nervous system (CNS) PFS as assessed by CNS BICR, PFS as assessed by investigator, ORR as assessed by BICR and investigator, OS and safety.

。关键的次要终点包括中枢神经系统（CNS）PFS（由CNS BICR评估），PFS（由研究者评估），ORR（由BICR和研究者评估），OS和安全性。

TROPION-Lung14 will enroll approximately 580 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov.

TROPION-Lung14将在亚洲，欧洲，北美，大洋洲和南美招募约580名患者。有关更多信息，请访问ClinicalTrials.gov。

About TROPION-Lung15

关于TROPION-Lung15

TROPION-Lung15 is a global, multicenter, open-label, three-arm phase 3 trial where patients will be randomized in a 1:1:1 ratio to evaluate the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) as monotherapy or in combination with osimertinib (80 mg) versus platinum-based doublet chemotherapy (pemetrexed in combination with carboplatin or cisplatin followed by pemetrexed maintenance) in adult patients with locally advanced or metastatic nonsquamous NSCLC with at least one EGFR mutation (G719X, Ex19del, S768I, L858R, and/or L861Q) and with disease progression following prior treatment with osimertinib..

TROPION-Lung15是一项全球性、多中心、开放标签的三臂3期临床试验，患者将以1:1:1的比例随机分组，以评估达托单抗-德鲁替康（6.0 mg/kg）作为单一疗法或联合奥西替尼（80 mg）与铂类双联化疗（培美曲塞联合卡铂或顺铂，然后培美曲塞维持治疗）对至少有一种EGFR突变（G719X、Ex19del、S768I、L858R和/或L861Q）的局部晚期或转移性非鳞癌成年患者的疗效和安全性（以及先前用osimertinib治疗后的疾病进展）。。

The dual primary PFS endpoints of TROPION-Lung15 are PFS as assessed by BICR for datopotamab deruxtecan monotherapy versus chemotherapy and datopotamab deruxtecan in combination with osimertinib versus chemotherapy. Key secondary endpoints include investigator-assessed CNS PFS as assessed by CNS BICR, ORR and DoR as assessed by BICR, OS and safety..

TROPION-Lung15的双重主要PFS终点是通过BICR评估的PFS，用于达托单抗-德鲁替康单药治疗与化疗以及达托单抗-德鲁替康联合奥西替尼与化疗。关键的次要终点包括研究者评估的中枢神经系统PFS，由中枢神经系统BICR，ORR和DoR评估，由BICR，OS和安全性评估。。

TROPION-Lung15 will enroll approximately 630 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov.

TROPION-Lung15将在亚洲，欧洲，北美，大洋洲和南美招募大约630名患者。有关更多信息，请访问ClinicalTrials.gov。

About Advanced Non-Small Cell Lung Cancer

关于晚期非小细胞肺癌

Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.1 NSCLC is the most common type of lung cancer, accounting for about 85% of cases.2 Approximately 75% and 25% of NSCLC tumors are of nonsquamous or squamous histology, respectively, with EGFR mutations occurring in 14% to 38% of all NSCLC tumors worldwide.3,4 A majority of EGFR mutations occur in tumors with nonsquamous histology.5.

2022年全球诊断出近250万例肺癌病例.1 NSCLC是最常见的肺癌类型，约占病例的85%.2约75%和25%的NSCLC肿瘤分别为非鳞状或鳞状组织学，EGFR突变发生在全球所有NSCLC肿瘤的14%至38%[3,4]。大多数EGFR突变发生在非鳞状组织学肿瘤中。

For patients with tumors that do not express a known actionable genomic alteration (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET or MET), the current first-line standard of care in the metastatic setting is an immune checkpoint inhibitor and/or platinum-based chemotherapy based on PD-L1 expression.6,7,8 For certain patients with tumors that have EGFR mutations, the established first-line treatment in the metastatic setting is an EGFR TKI.9 While these treatment strategies have improved outcomes in the first-line metastatic setting, most patients eventually experience disease progression.10,11,12.

对于不表达已知可行基因组改变（例如EGFR，ALK，ROS1，NTRK，BRAF，RET或MET）的肿瘤患者，目前转移环境中的一线护理标准是免疫检查点抑制剂和/或基于PD-L1表达的铂类化疗[6,7,8]。对于某些具有EGFR突变的肿瘤患者，在转移环境中建立的一线治疗是EGFR TKI[9]。虽然这些治疗策略在一线转移环境中改善了预后，但大多数患者最终会经历疾病进展[10,11,12]。

TROP2 is a protein broadly expressed in the majority of NSCLC tumors.13 There is currently no TROP2 directed ADC approved for the treatment of lung cancer.8,9

TROP2是一种在大多数NSCLC肿瘤中广泛表达的蛋白质[13]。目前还没有TROP2指导的ADC被批准用于治疗肺癌[8,9]

About Datopotamab Deruxtecan (Dato-DXd)

关于达托帕马·德鲁克斯坦（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 six DXd 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指导的ADC。datopotamab deruxtecan使用Daiichi Sankyo专有的DXd ADC技术设计，是Daiichi Sankyo肿瘤学管道中的六个DXd ADC之一，也是阿斯利康ADC科学平台中最先进的程序之一。

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 global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings..

一项全面的全球临床开发计划正在进行中，超过20项试验评估了达托单抗deruxtecan在多种癌症中的疗效和安全性，包括NSCLC，三阴性乳腺癌和HR阳性，HER2阴性乳腺癌。该计划包括7项肺癌3期临床试验和5项乳腺癌3期临床试验，评估达托单抗-德鲁替康作为单一疗法以及在各种情况下与其他抗癌治疗相结合。。

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 (Dato-DXd) 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..

第一三共和阿斯利康于2019年3月达成全球合作，共同开发ENHERTU并于2020年7月将其商业化，datopotamab deruxtecan（Dato DXd）在日本除外，在日本，第一三共为每个ADC保留独家权利。Daiichi Sankyo负责ENHERTU和datopotamab deruxtecan的制造和供应。。

About the ADC Portfolio of Daiichi Sankyo

关于第一三共的ADC投资组合

The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.

Daiichi Sankyo ADC组合由七个临床开发中的ADC组成，这些ADC由Daiichi Sankyo内部发现的两个不同的ADC技术平台精心打造而成。

The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where 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. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca.

临床开发中最深入的ADC平台是Daiichi Sankyo的DXd ADC技术，其中每个ADC由单克隆抗体组成，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）。DXd ADC投资组合目前由ENHERTU（一种HER2导向的ADC）和datopotamab deruxtecan（Dato DXd）（一种TROP2导向的ADC）组成，它们正在与阿斯利康（AstraZeneca）联合开发并在全球商业化。

Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo..

Patritumab deruxtecan（HER3 DXd），一种HER3导向的ADC，ifinatamab deruxtecan（I-DXd），一种B7-H3导向的ADC，以及raludotatug deruxtecan（R-DXd），一种CDH6导向的ADC，正在与默克公司联合开发和全球商业化。DS-3939是一种TA-MUC1定向的ADC，由Daiichi Sankyo开发。。

The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.

第二个Daiichi Sankyo ADC平台由连接到修饰的吡咯并苯并二氮杂卓（PBD）有效载荷的单克隆抗体组成。DS-9606是一种CLDN6定向的PBD ADC，是利用该平台进行临床开发的几个计划ADC中的第一个。

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 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，DS-3939和DS-9606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.

Daiichi Sankyo是一家创新的全球医疗保健公司，致力于社会的可持续发展，发现、开发和提供新的护理标准，以丰富世界各地的生活质量。拥有120多年的经验，第一三共利用其世界一流的科学和技术，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。。

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References

参考文献

1 World Health Organization. Global Cancer Observatory: Lung. Accessed October 2024.

1世界卫生组织。全球癌症观察站：肺。2024年10月访问。

2 Economopoulou P, et al. Ann Transl Med. 2018; 6(8):138

2 Economopoulou P，等.医学学报.2018；6(8):138

3 National Cancer Institute. SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer, CSR 1975-2017. Accessed October 2024.

3国家癌症研究所。SEER癌症统计概况：肺癌和支气管癌，CSR 1975-2017。2024年10月访问。

4 Pretelli G, et al. Int J Mol Sci. 2023; 24, 8878.

4 Pretelli G等人，《国际分子科学杂志》。2023;24, 8878.

5 Prabhakar C. Translational Lung Cancer Research. 2015; 4(2), 110-118.

5 Prabhakar C.转化型肺癌研究。2015年；4（2），110-118。

6 Mok TSK, et al. Lancet. 2019 May 4;393(10183):1819-1830.

6 Mok Tsk等人，《柳叶刀》。2019年5月4日；393（10183）：1819-1830。

7 Brahmer J.R. et al. KEYNOTE-024 5-year OS update. ESMO 2021 Virtual Congress. 2021 Sept 16 – 20; Abstract LBA51.

7 Brahmer J.R.等人，KEYNOTE-024 5年操作系统更新。ESMO 2021虚拟大会。2021年9月16日至20日；。

8 Rodríguez-Abreau D, et al. Ann Onc. 2021 Jul;32(7):881-895.

8 Rodríguez Abreau D等人，Ann Onc。2021年7月；32（7）：881-895。

9 American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer. Accessed October 2024.

9美国癌症协会。非小细胞肺癌的靶向药物治疗。2024年10月访问。

10 Chen R, et al. J Hematol Oncol. 2020:13(1):58.

Chen R等人，J.血液肿瘤。2020:13（1）：58。

11 Majeed U, et al. J Hematol Oncol. 2021;14(1):108.

11 Majeed U等人，J.血液肿瘤。2021年；14（1）：108。

12 Pircher A, et al. Anticancer Research. 2020;70(5):287-294.

12 Pircher A等人。抗癌研究。；70（5）：287-294。

13 Mito R, et al. Pathol Int. 2020;70(5):287-294.

13 Mito R等人，Pathol Int.2020；70（5）：287-294。