Datopotamab Deruxtecan

TOKYO, Japan & BASKING RIDGE, NJ, USA I June 09, 2025 I The first patient has been dosed in the DESTINY-Endometrial01 phase 3 trial evaluating ENHERTU ® (trastuzumab deruxtecan) in combination with rilvegostomig or pembrolizumab versus platinum-based chemotherapy (carboplatin and paclitaxel) in combination with pembrolizumab as a first-line therapy in patients with HER2 expressing (IHC 3+/ 2+), mismatch repair proficient (pMMR) primary advanced or recurrent endometrial cancer. DESTINY-Endometrial01 will be conducted in collaboration with The GOG Foundation, Inc. (GOG-F) and the European Network of Gynecological Oncological Trial (ENGOT). ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). Endometrial cancer that is recurrent or diagnosed in advanced stages has a median overall survival of up to 30 months. 1 While there have been recent treatment advances, there is still a need to further improve outcomes for patients. HER2 expression (IHC 3+/2+) is associated with aggressive disease and is present in 18% to 56% of endometrial cancers. 2,3,4,5,6 There currently are no HER2 directed medicines approved in the first-line endometrial cancer setting. “Following the positive results in the endometrial cancer cohort of DESTINY-PanTumor02, which contributed to a tumor agnostic approval for previously treated patients with HER2 positive metastatic tumors in several regions, we are initiating this first phase 3 trial of ENHERTU in the first-line setting of advanced endometrial cancer,” said Mark Rutstein, MD, Head, Therapeutic Area Oncology Development, Daiichi Sankyo. “The DESTINY-Endometrial01 trial will help us better understand the role of ENHERTU in combination with immunotherapy as a potential treatment strategy to help improve outcomes compared to the current standard of care in this specific gynecological cancer setting.” About DESTINY-Endometrial01 DESTINY-Endometrial01 is a global, multicenter, randomized, open-label phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) in combination with rilvegostomig or pembrolizumab versus platinum-based chemotherapy (carboplatin and paclitaxel) in combination with pembrolizumab as a first-line therapy in patients with HER2 expressing (IHC 3+/2+), pMMR, primary advanced (stage III/IV) or first recurrent endometrial cancer of any histologic subtype except sarcoma. Patients will be randomized in a 1:1:1 ratio to receive either ENHERTU in combination with rilvegostomig, ENHERTU in combination with pembrolizumab or platinum-based chemotherapy in combination with pembrolizumab. The primary endpoint is progression-free survival (PFS) as assessed by blinded independent central review (BICR). The key secondary endpoint is overall survival. Additional secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response and safety. DESTINY-Endometrial01 will enroll approximately 600 patients across multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov . Rilvegostomig is AstraZeneca’s PD-1/TIGIT bispecific antibody. The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd. (Nasdaq/TASE: CGEN). Pembrolizumab (KEYTRUDA ® ) is Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy. About Endometrial Cancer Endometrial cancer is the second most common gynecologic cancer and the sixth most common cancer among women worldwide. 7 Approximately 420,000 endometrial cancer cases were diagnosed in 2022, with more than 97,000 deaths globally. 8 Incidence and mortality rates of endometrial cancer are expected to increase by approximately 61% and 87% respectively by 2050. 9 Patients with advanced or recurrent endometrial cancer have a poor prognosis, with a median overall survival of up to 30 months. 1 Endometrial cancer comprises several molecular subtypes. 10 Approximately 20% to 30% of all endometrial cancers exhibit high microsatellite instability (MSI) due to a defective mismatch repair system and are classified as MSI-high or MMR deficient (dMMR). 10 The remaining 70% to 80% of cases are considered mismatch repair proficient (pMMR) tumors. 10 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors. 11 HER2 expression (IHC 3+/ 2+) is present in 18% to 56% of endometrial cancers and is associated with markers of aggressive disease. 2,3,4,5,6 HER2 expression is observed almost exclusively in pMMR tumors. 2 Standard of care first-line treatment of advanced or recurrent endometrial cancer has long included carboplatin plus paclitaxel. 12 The treatment paradigm has recently evolved to incorporate an immune checkpoint inhibitor with carboplatin and paclitaxel, particularly for patients with dMMR endometrial cancer; however, the benefit of this treatment regimen in pMMR endometrial cancer is less pronounced. 13,14,15,16 There currently are no HER2 directed medicines approved in the first-line endometrial cancer setting. About ENHERTU ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) 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 program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. ENHERTU (5.4 mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. ENHERTU (5.4 mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/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 (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that has progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. ENHERTU (5.4 mg/kg) is approved in more than 60 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 ( ERBB2 ) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (6.4 mg/kg) is approved in more than 70 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 , DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (5.4 mg/kg) is approved in Brazil, Israel, Russia, Saudi Arabia, Switzerland, Taiwan, U.K. and the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02 , DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. About the ENHERTU Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other anti-cancer therapies across multiple HER2 targetable cancers. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and DATROWAY ® 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 DATROWAY. About the ADC Portfolio of Daiichi Sankyo 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. 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 DATROWAY, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. 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 & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. 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. 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. Please see accompanying full Prescribing Information , including Boxed WARNINGS, and Medication Guide . About Daiichi Sankyo 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. For more information, please visit www.daiichisankyo.com . References 1 Coleman RL, et al. JHEOR .2023;10(2):82-90. 2 Vermij L, et al. Cancers (Basel) . 2020;13(1):44. 3 Buza N. Arch Pathol Lab Med . 2021;145(6):687–691. 4 Uzunparmaek B, et al. Ann Oncol . 2023;34(11):1035-1046. 5 Semiz SH, et al. Turkish Journal of Pathology .2023;39(1):055-063 6 Halle MK, et al. Br J Cancer . 2017;118(3):378-387. 7 GLOBOCAN. International agency for research on cancer (IARC): Age-Standardized Rate (World) per 100 000, Incidence and Mortality, Females, all ages in 2022 . Accessed June 2025. 8 GLOBOCAN. Uterine Cancer Fact Sheet . Accessed June 2025. 9 World Health Organization. Cancer Tomorrow: Corpus Uteri. Accessed June 2025. 10 Corr B, et al. BMJ Med . 2022;1:e000152. 11 Omar N, et al. Pathogenesis . 2015 2(3):1-9. 12 Miller DS, et al. J Clin Oncol . 2020;38:3841–3850. 13 Mirza MR, et al. N Engl J Med . 2023:8;388:2145–2158. 14 Eskander RN, et al. N Engl J Med . 2023;388:2159–2170. 15 Westin SN, et al. J Clin Oncol . 2024;42:283–299. 16 Colombo N, et al. Lancet Oncol . 2024;25:1135–1146. SOURCE: Daiichi Sankyo

吴妮 | 撰文又一 | 编辑每年ASCO大会都会引来一场全球生物医药人的大型迁徙，他们从世界各地聚集到美国芝加哥的麦考密克会展中心，汲取新鲜的信息和养料。 今年ASCO依旧规模盛大，参会人数高达4.5万余人，等候入场的队伍流动很快，即便如此也要二三十分才能领到胸牌进场。ASCO会场外围提供了一个开放的空间，让没有注册参会的人也能来互相约见。  中国研究者存在感越来越强，今年有73项来自中国学者的口头报告研究分享，其中11项为最新突破摘要（Late Breaking Abstract，LBA）。几乎每场专场都会有中国研发者的presentation。  AACR主要聚焦于基础科研成果，ASCO更倾向于展示最新临床研究成果。一位临床研发从业者介绍，“我个人感觉，比起基础科研和科学成果转化，中国药品临床开发的突破性进展更多。” 三四年前，中国药企在ASCO大会上的标签还是me too。但是现在，海外的同行不再用me too来概括中国药企，而是给予更多认可、尊重，好奇中国的创新药长什么样子。 “我们公司准备做口头报告的时候，整个会场涌进很多人，前排基本坐满。等到整个新药临床数据分享的session结束后，他们就忽然就走了，前后的热度有非常明显的差别。”一家创新企业人士说。 为国内创新药研究作报告的speaker有海外PI，也有来自国内的PI。即便有的国内PI英语口音一般，在分享结束后依然有很多人围上去，可见对中国制药的热情。 在各自的报告结束后，中国的研究者和药企人士马不停蹄地进行社交，“CEO会借此机会和PI深入交流，同时应对BD合作的沟通。负责临床开发的人士也会向PI了解他们承接的不同药物的试验情况，不同科室的临床观察和应对。还会关注biomarker相关的研究，对早期的biomarker进行分析，这涉及到后面临床策略的制定。” -01-摘掉me too标签今年参会的人都有一个相同的感受，无论摘要还是口头报告，来自于中国的科学家、研究者成果都很多，中国药企从这些成果中展现出不同以往的创新力。 这一趋势在新兴赛道上表现的更明显。上述临床研发从业者称，“在传统的赛道上，其他国家的药企已经形成平台效应，在多年积累的基础上进行成果转化的效率超过国内药企。但是在最新的赛道上面，国内药企是领先的。” 特别是双抗、ADC和CAR-T。 科伦博泰的TROP2 ADC成为合作方默沙东今年的门面之一，SKB264针对EGFR突变肺癌（III期）、三阴性乳腺癌（TNBC）的临床数据入选口头报告，前者给康方施加了一些压力，后者欲与DS-8201比肩。映恩生物的B7H3 ADC药物DB-1311在前列腺癌后线治疗中超预期的临床潜力，ORR达27.9%，6个月无进展生存率86.6%。 信达生物以口头报告形式报道了PD-1/IL-2α-bias双抗IBI363在治疗非小细胞肺癌、结直肠癌、黑色素瘤的I/II期临床数据，均展示出超越现有标准疗法的疗效信号及可控的安全性。 泽璟制药公布了ZG-006（CD3/DLL3/DLL3）三抗药物治疗小细胞肺癌II期数据，客观缓解率高达66.7%，具有成为BIC分子的潜力。 K药又迎来一位来自中国的挑战者，中国生物制药报告了贝莫苏拜单抗+安罗替尼（“得福组合”）在肺鳞癌一线治疗中与K药头对头 III 期临床研究成果。结果显示，在全人群中，“得福组合”中位PFS达到11.0个月，较帕博利珠单抗治疗提升3.9个月，疾病进展或死亡风险降低30%（HR=0.70）。 CAR-T领域，科济药业口头报告了CLDN18.2的CAR-T疗法（satri-cel）针对晚期胃/食管胃结合部腺癌的确证性II期临床试验研究结果，证实satri-cel可让晚期胃癌患者生存期延长44%。科济计划于6月向国家药监局提交上市申请，satri-cel很可能会成为全球首个上市的实体瘤CAR-T产品。 中国创新药从追随到引领的转变就发生在两三年之间。2024年,中国创新药共完成94笔交易,总金额达到519亿美元。而2025年截至目前，BD交易总额已超455亿美元。放在5年前、10年前不敢想象能够达到这样的规模。-02-PD-(L)1，经典永不过时全体起立为DS-8201鼓掌的一幕并不是每年都会发生。今年ASCO上虽然亮点很多，但更多是组合式创新，以及在预期范围内的进展。多位参会人员表示，特别新的靶点倒是没有看到，主要是不同的双抗/多抗和联用方案。 在众多组合中，PD-(L)1依然是焦点，PD-(L)1/VEGF的双靶点抗体更是焦点中的焦点。 EGFR突变是非小细胞肺癌中最常见的突变类型，之前EGFR突变的患者用PD-1是没有效果的。现在临床试验已经验证PD-(L)1/VEGF双抗对EGFR突变二线治疗的疗效，将来肯定会推向一线治疗，这样就会对现在的一线药物比如阿昔替尼等TKI药物带来很大冲击，也可能取代PD-(L)1的市场地位。 作为PD-(L)1/VEGF双抗开山鼻祖，SUMMIT今年没有在ASCO上报道其PD-1/VEGF双抗AK112，但是在会前发布了其联合化疗用于第二线 EGFR 突变NSCLC的全球 III 期（HARMONi）临床试验的初步顶线数据，结果显示，PFS有统计学显著改善，OS没有达到统计学显著性，但表现出的积极趋势依然有意义。宜明昂科有三个管线在ASCO上作报告，宜明昂科董事长田文志发现受关注最多的还是PD-L1/VEGF双抗AXN-2510(IMM2510）。“我们开了一个早餐会，邀请二三十家投资机构到场，向他们介绍IMM2510的临床试验进展。投资人主要是想了解IMM2510潜在价值，从而为制订下一步投资策略提供参考依据。” 除了投资机构，田文志也在频繁地和MNC的人士对接。宜明昂科已经将IMM2510双抗全球权益授权给Instil Bio，但许多MNC对这个赛道的兴趣与日俱增，所以进一步授权给MNC是个大概率事件。  作为一款基石药物，PD-(L)1的商业传奇还要持续很久，目前PD-(L)1和VEGF的联合最热，第二波热潮就是PD-(L)1单抗/双抗和其他抗体、ADC的联合。基石药业有一款PD-1/VEGF/CTLA-4三抗（CS2009），一位研发从业者认为，“Summit的PD-1/VEGF双抗达到了PFS的主要终点，OS还没有达到终点。如果将来三抗能够大幅度提升疗效，使OS达到终点，这会是一个颠覆性创新。”PD-(L)1和ADC联用的疗效也逐渐被证实。今年ASCO大会阿斯利康公布靶向TROP2的ADC Dato-DXd联合帕博利珠单抗±铂类化疗（双联方案或三联方案）一线治疗晚期NSCLC的最新数据，进一步证实在高和低PD-L1表达亚组中均有疗效，且联合治疗的耐受性符合预期。科伦博泰公布了TROP2 ADC芦康沙妥珠单抗+PD-L1单抗塔戈利单抗一线治疗非鳞NSCLC的Ⅱ期研究数据，确认ORR为59.3%，mDoR为16.5个月，mPFS为15.0个月。 靶向PD-L1的ADC也揭开面纱，辉瑞PF-08046054和宜联生物/复宏汉霖的 HLX43都在ASCO上公布了不错的I期数据，证明了PD-L1 ADC的成药性。 田文志认为，“PD-(L)1单抗与ADC确实是一个不错的选择，早期数据尤其惊艳。但是ADC药物最大的挑战在于毒性，未来就要看PD-(L)1与ADC的组合能否在有效性和安全性上达到一个平衡，保证患者可以持续用药。如果安全性不能保证，就无法达到显著的PFS获益，更不会有OS获益。” -03-和海外对齐认知度 Claudin 18.2作为实体瘤领域的热门治疗靶点，今年已经有很多研究成果，比如信达生物的CLDN18.2 ADC，齐鲁制药 Claudin18.2/CD3 的TCE，传奇生物和科济药业的Claudin18.2 CAR-T等等。 同靶点的布局者基本了解彼此的进度和状态，有的时候研究者也会给药企反馈其他药物的试验情况。“但是在看待这些数据的时候，必须要带着对于疾病领域深入的理解。有的时候信息太多或者是数据太多，不一定会让人更清晰，反而会更困惑。因为一些临床研究统计的患者数据较少，这种时候我们会让数据再飞一会，等待数据更成熟的时候，比如说在二期即将进入三期的阶段，再去重点关注他们的布局。”上述临床研发人士说道。 这一思路可以应用到任何一个赛道。制药行业的modality日新月异，任何热门癌种、适应症、剂型的竞争都很激烈。 这也是大家乐此不疲参加国际大会的原因。身在其中的研发者在彼此了解的过程中也能更准确找到自己的定位，还能触发新的思考。 上述创新企业人士是第一次来ASCO，但此行让她多了一份自信，“我们能想到的、做到的和那些很成熟的公司是一致的，knowledge gap并不大。” 总的来说，2025年ASCO，没有太多意外。 这一方面意味着全球研发者的很多概念得到确证，在理想与现实的博弈中占据上风。 而对中国创新药从业者来说，这意味着，我们的认知水平和研究成果没有落后于人，这会是中国创新药迎来deepseek时刻的开端。 ......欢迎添加作者交流：吴妮：nora4409