Fam-trastuzumab deruxtecan-NXKI

BASKING RIDGE, NJ & RAHWAY, NJ, USA I June 18, 2025 I The first patient has been dosed in the IDeate-Prostate01 phase 3 trial evaluating the efficacy and safety of investigational ifinatamab deruxtecan (I-DXd) versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) with disease progression during or after treatment with an androgen receptor pathway inhibitor. Ifinatamab deruxtecan is a specifically engineered, potential first-in-class B7-H3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and Merck (NYSE: MRK), known as MSD outside of the United States and Canada. While localized prostate cancer has a five-year survival rate of more than 90%, survival decreases to 31% in the advanced or metastatic stage. 1 Current standard of care for patients with mCRPC includes treatment with androgen receptor pathway inhibitors followed by taxane-based chemotherapy. 2-5 However, due to poor prognosis associated with previously treated mCRPC, many patients do not receive subsequent therapy, reinforcing the need for new approaches to improve outcomes. 6 “Despite the emergence of new therapies, the current treatment landscape for patients with metastatic castration-resistant prostate cancer is challenging, and there is a need for new treatments,” said Mark Rutstein, MD, Head, Therapeutic Area Oncology Development, Daiichi Sankyo. “Following the promising results seen in our earlier phase trial, IDeate-Prostate01 has been initiated to evaluate whether ifinatamab deruxtecan may replace standard taxane-based chemotherapy as a potential treatment strategy in patients with metastatic castration-resistant prostate cancer with disease progression during or after treatment with androgen receptor pathway inhibitors.” “IDeate-Prostate01 marks the initiation of the third pivotal trial in the ifinatamab deruxtecan development program and reinforces our commitment to addressing critical unmet needs for patients,” said Marjorie Green, MD, Senior Vice President and Head of Oncology, Global Clinical Development, Merck Research Laboratories. “Our continued progress in the exploration of this potential first-in-class B7-H3 antibody drug conjugate in collaboration with Daiichi Sankyo, speaks to our pursuit of novel science in the hopes of making a difference for patients in need of new options.” The initiation of IDeate-Prostate01 is based on results from the IDeate-PanTumor01 phase 1/2 trial previously presented at the 2022 and 2023 European Society of Medical Oncology (ESMO) Congresses where ifinatamab deruxtecan showed promising responses in heavily pretreated patients with mCRPC. About the IDeate-Prostate01 Trial IDeate-Prostate01 is a multicenter, open-label, randomized phase 3 trial evaluating the safety and efficacy of ifinatamab deruxtecan (12 mg/kg) versus docetaxel (75 mg/m 2 ) plus corticosteroid in patients with mCRPC. Eligible patients must have received prior treatment with one or two androgen receptor pathway inhibitors and experienced disease progression during or after at least eight weeks of treatment. The dual primary endpoints of IDeate-Prostate01 are overall survival and radiographic progression-free survival. Secondary endpoints include objective response rate, time to first subsequent therapy, duration of response, time to pain progression, time to prostate-specific antigen (PSA) progression, PSA response, time to first symptomatic skeletal-related event and safety. IDeate-Prostate01 will enroll approximately 1,440 patients across Asia, Europe, North America and Oceania. For more information, please visit ClinicalTrials.gov . About Metastatic Castration-Resistant Prostate Cancer Prostate cancer is the second most common cancer in men, and the fifth leading cause of cancer death in men worldwide. 7 Nearly 1.5 million prostate cancer cases were diagnosed in 2022, with approximately 400,000 deaths globally. 7 While localized prostate cancer has a five-year survival rate of more than 90%, survival decreases to 31% in advanced or metastatic stage. 1 Approximately 10% to 20% of early-stage prostate cancer cases progress to metastatic disease within five years of treatment on hormonal therapies such as androgen deprivation therapy. 8,9 Current standard of care for patients with mCRPC includes treatment with androgen receptor pathway inhibitors followed by taxane-based chemotherapy. However, due to poor prognosis associated with previously treated mCRPC, many patients do not receive subsequent therapy, reinforcing the need for new approaches to improve outcomes. 6 About B7-H3 B7-H3 is a transmembrane protein that belongs to the B7 family of proteins, which bind to the CD28 family of receptors that includes PD-1. 10,11 B7-H3 is overexpressed in a wide range of cancer types, including mCRPC and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target. 12-15 There are currently no B7-H3 directed medicines approved for the treatment of any cancer. About Ifinatamab Deruxtecan Ifinatamab deruxtecan (I-DXd) is an investigational potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Ifinatamab deruxtecan has been granted orphan drug designation by the U.S. Food and Drug Administration, European Commission, Japan Ministry of Health, Labour and Welfare and Taiwan Food and Drug Administration for the treatment of small cell lung cancer. About the Ifinatamab Deruxtecan Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ifinatamab deruxtecan across multiple B7-H3 targetable cancers. Trials in combination with other anticancer treatments also are underway. About the Daiichi Sankyo and Merck Collaboration Daiichi Sankyo and Merck entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply. In August 2024 , the global co-development and co-commercialization agreement was expanded to include gocatamig (MK-6070/DS3280), which the companies will jointly develop and commercialize worldwide, except in Japan where Merck will maintain exclusive rights. Merck will be solely responsible for manufacturing and supply for gocatamig. 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 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. 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 needs. For more information, please visit www.daiichisankyo.com . Merck’s Focus on Cancer Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www-merck-com.libproxy1.nus.edu.sg/research/oncology . About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . References: SOURCE: Merck

如果说DS-8201是HER2 ADC的天花板，恐怕没人反对。自上市起，这一现象级产品不断开疆拓土，正以前所未有的速度重构HER2靶向治疗标准。那么，面对DS-8201的碾压，中国药企在HER2赛道上如何突出重围？  01  DS-8201的护城河有多深？DS-8201（德曲妥珠单抗，T-DXd，Enhertu）是第一三共/阿斯利康的一款靶向HER2靶点的第三代ADC产品，由于DS-8201将不可裂解连接子升级为可裂解连接子，并采用定点偶联的偶联方式，其药物抗体比（DAR）可达到8，与传统HER2 ADC相比，具有更强大的肿瘤杀伤力。自2019年12月，DS-8201首次获FDA批准用于HER2阳性乳腺癌三线治疗以来，DS-8201一路披荆斩棘。目前，DS-8201还将适应症拓展至HER2阳性晚期乳腺癌二线治疗、HER2低表达晚期乳腺癌的二线治疗、局部晚期或转移性HER2阳性成人胃或胃食管结合部腺癌患者的三线治疗、HER2突变的、不可切除或转移性非小细胞肺癌的治疗，以及不可切除或转移性的HER2阳性实体瘤的治疗等。凭借不断拓展的适应症，DS-8201已成为HER2 ADC领域天花板级别的存在。2024年，其销售额突破37亿美元，再次登顶ADC药物销量榜首。不仅如此，在前不久召开的2025ASCO上，第一三共/阿斯利康还公布了DS-8201的DESTINY-Breast09最新研究成果，该研究旨在比较DS-8201与帕妥珠单抗联合治疗方案，相较于当前一线标准治疗方案（紫杉烷+曲妥珠单抗+帕妥珠单抗，THP），在HER2阳性转移性乳腺癌患者中的疗效。结果显示，DS-8201+帕妥珠单抗组在主要终点PFS上展现出显著优势。该组合使中位PFS达到40.7个月，相比对照组THP的26.9个月，延长了近14个月（HR=0.56，p＜0.00001)；另外，DS-8201+帕妥珠单抗组的ORR为85.1%，高于THP组的78.6%；其中完全缓解率（CR）为15.1%，几乎是THP组的两倍（8.5%）。在治疗24个月后，DS-8201+帕妥珠单抗组仍有73%的患者维持缓解状态，而THP组仅为55%。目前，总生存期数据尚不成熟。DESTINY-Breast09是十多年来首次在HER2阳性转移性乳腺癌患者群体中，与当前一线标准治疗方案相比，展现出优越疗效的研究，使DS-8201联合帕妥珠单抗有望成为一线HER2阳性治疗方案的重要选择，有望改写其一线治疗标准。至此，DS-8201在乳腺癌领域构建了坚不可摧的壁垒。面对DS-8201的“封锁”，中国药企在HER2赛道也不甘示弱，他们或从技术路线，或从适应症选择等，在该赛道迎难而上。  02  差异化定位，精准化破局就在刚刚过去的5月29日，恒瑞医药自主研发的HER2 ADC新药SHR-A1811（瑞康曲妥珠单抗）国内附条件获批上市，用于治疗HER2阳性且既往接受过至少一种系统治疗的不可切除的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者。据瑞康曲妥珠单抗治疗HER2 突变 NSCLC 患者的 II 期临床试验，数据显示，在94例既往接受过至少一种系统治疗的局部晚期或转移性HER2突变NSCLC患者中，主要研究终点ORR 为73.4%，亚组 ORR 获益趋势与总体人群一致。研究结果达到方案预设的优效标准。在NSCLC这一大适应症领域，之前仅有DS-8201一款HER2 ADC获批，市场远未饱和，恒瑞此时入局，无疑将占据先发优势。值得一提的还有荣昌生物，其HER2 ADC——维迪西妥单抗于2021年6月在国内获批上市，用于HER2过表达局部晚期或转移性胃癌（包括胃食管结合部腺癌）患者的三线治疗，同时也是首个上市的国产ADC。上市仅6个月后（2021年12月），维迪西妥单抗再次获批治疗既往接受过系统化疗且HER2阳性的局部晚期或转移性尿路上皮癌患者。在尿路上皮癌赛道，DS8201尚未获批，国内其他同靶点在研药物尚处于早期临床阶段，维迪西妥单抗的差异化竞争优势凸显。此外，今年5月9日，维迪西妥单抗治疗HER2阳性存在肝转移晚期乳腺癌患者的适应症在国内获批上市，成为全球首个用于该适应症的ADC药物。公开数据显示，约45%的HER2阳性晚期乳腺癌患者伴有肝转移，这类患者预后极差，且尚无推荐的标准治疗方案。据维迪西妥单抗在肝转移晚期HER2阳性乳腺癌患者的Ⅲ期临床研究，结果显示，与对照组拉帕替尼联合卡培他滨（mPFS 4.9个月）相比，维迪西妥单抗治疗组的mPFS达到9.9个月，实现了翻倍，而且风险比（HR）为0.56，意味着将疾病进展或死亡风险降低了44%，对于该适应症而言，此HR下降幅度十分可观。目前，OS数据尚不成熟，但维迪西妥单抗治疗组有获益趋势，两组中位OS分别为未达到和25.92个月。无论是恒瑞还是荣昌生物，在HER2 ADC这个拥挤的赛道，均通过立足差异化适应症布局，来避开DS-8201在乳腺癌领域打造的坚固堡垒，实现精准化破局。尤其是荣昌生物，从尿路上皮癌到肝转移晚期乳腺癌，创造了一个又一个精准医疗范例。最近，荣昌生物还在推进维迪西妥单抗联合PD1+化疗一线治疗 HER2低表达胃癌的Ⅲ期研究，目前全球尚无药物获批治疗 HER2 低表达胃癌。一旦成功，将意味着维迪西妥单抗在胃癌适应症中HER2高中低表达的全覆盖。与恒瑞和荣昌生物在适应症差异化打法不同，国内还有一些药企从技术路线突围。  03  多元化技术路线，围剿DS-8201在恒瑞的瑞康曲妥珠单抗获批同一天，百济神州/Zymeworks的HER2双抗泽尼达妥单抗（zanidatamab，ZW25）也在国内附条件获批上市，用于既往接受过全身治疗的HER2高表达不可切除局部晚期或转移性胆道癌患者。泽尼达妥单抗作为一种HER2靶向双抗，可以同时结合两个非重叠的HER2表位，从而引发HER2和HER3信号抑制，以及从细胞表面去除HER2蛋白和增强免疫效应功能，促进抗肿瘤活性。在针对HER2高表达胆道癌（HER2 免疫组化3+）的HERIZON-BTC-01研究中，结果显示，ORR为52%，中位DOR为14.9个月。值得注意的是，HER2阳性胆道癌适应症也是DS-8201布局方向之一，但已被泽尼达妥单抗捷足先登。除此次获批适应症外，泽尼达妥单抗还布局了一线胆道癌、二线及以上乳腺癌以及一线胃食管腺癌等多个高发癌种的适应症。同样打算以双抗破局的还有石药集团/康宁杰瑞，两家合作开发的HER2双抗KN-026，布局了HER2阳性胃癌的二线及后线治疗，以期与即将入局胃癌一线治疗的DS-8201，形成差异化补位。除双抗外，国内正大天晴正在进行HER2双抗ADC的探索。旗下TQB2102是一种靶向HER2两个非重叠表位的双抗ADC，具有更强的结合、内化效率和杀伤作用，对HER2中低表达的肿瘤具有优势。同时，双表位的特异性和ADC的作用机制有望从结构创新上，来解决DS-8201间质性肺炎发生率高的问题。基于此机制，正大天晴已启动TQB2102与罗氏T-DM1（二代HER2 ADC药物）在HER2阳性晚期乳腺癌中的头对头临床试验，并且启动了TQB2102在HER2低表达复发/转移性乳腺癌的III期研究。另外，TQB2102在晚期实体瘤患者中的安全性和有效性探索的首次人体I期临床研究，已入选2025ASCO口头报告，初步数据显示，在181例晚期实体瘤患者中，HER2阳性乳腺癌ORR为51.3%，HER2低表达乳腺癌ORR为51.5%，HER2高表达（HER2 免疫组化3+）结直肠癌ORR为34.8%，HER2阳性胃或胃食管结合部腺癌ORR为70%。DS-8201，从2019年获得FDA批准上市开始，已成为HER2靶点命运的改写者，在它抛出一项又一项超乎预期的临床数据后，业界一度以为中国HER2赛道玩家的故事讲不下去了。然而中国药企再次展现出了创新韧性，他们要么以结构创新，要么以适应症差异化布局，来卷质量，卷安全性，最终在DS-8201的护城河之外，撕开了一道口子。参考：1.CDE官网、各公司官微2.https://www.cancertreatmentreviews.com/article/S0305-7372(22)00042-1/fulltext.3.2025 ASCO abr3003.   识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。