Ifinatamab deruxtecan

2025年9月17日，一项在局部晚期、转移性或不可切除的实体瘤受试者中评价DS-3939a 的安全性、耐受性、药代动力学（PK）和初步疗效的全球性、多中心、开放性、首次人体、I/II 期研究成功在中国实现首例受试者给药。 　　这标志着该研究在中国迈出了重要的第一步。我们期待与各方继续紧密合作，加速DS3939a的临床开发进程。同时，我们热切希望更多患者能够有机会参与到DS3939-077研究中，并从中获益。研究团队将全力以赴更快地推进DS3939a的临床开发，期待早日将这一创新疗法惠及中国患者。 　　　关于DS3939-077临床研究　　　 　　DS3939-077研究是一项在局部晚期、转移性或不可切除的实体瘤受试者中评价DS-3939a的安全性、耐受性、药代动力学（PK）和初步疗效的全球性、多中心、开放性、首次人体、I/II 期研究。 　　本研究将分为2个部分入组受试者：剂量递增部分（第1部分）和剂量扩展部分（第2 部分）。第1部分的主要目的是评价DS-3939a的安全性和耐受性。第2部分的主要目的是评价DS-3939a的安全性、耐受性和初步疗效。 　　更多研究相关信息，可登陆https://clinicaltrials.gov及http://www.chinadrugtrials.org.cn网站查询。 　　　　　关于TA-MUC1　　　　　 　　MUC1是一种单次跨膜糖蛋白，MUC1的结构特征之一是其胞外域中存在20-125个数量不等的串联重复序列（TR）。每个TR 由20个氨基酸组成，具有5个潜在的O-糖基化位点。MUC1在上皮表面的顶端膜上表达，在正常组织中高度糖基化，为下层上皮提供保护。而MUC1在癌细胞中会失去细胞极性，并在细胞表面和细胞质内重新分布。MUC1在肿瘤中过表达会导致多种癌症的转移和预后不良（如胰腺癌和膀胱癌）。 　　由于某些唾液酸转移酶表达模式的变化而导致的异常糖基化，在肿瘤中MUC1上暴露出新的表位，被称为TA-MUC1。预计这种极化和糖基化的变化会增强抗体对TA-MUC1的可及性。由于TA-MUC1在大多数人类上皮癌中过表达，因此它是癌症治疗的一个有吸引力的靶点。 　　　　　关于DS3939a　　　　　 　　DS-3939a是一种靶向作用于TA-MUC1的ADC。其结构由重组人源化抗TA-MUC1抗体（使用中国仓鼠卵巢细胞系生成）、GGFG 四肽连接子和MAAA-1181a（拓扑异构酶I 抑制剂：DXd有效载荷）组成。药物抗体比为8。这项DXd-ADC 技术已应用于其他抗肿瘤产品（如德曲妥珠单抗），并在临床前研究中显示出强大的抗肿瘤活性，并且在癌症患者中表现出具有前景的疗效和安全性。 　　　　　　关于第一三共　　　　　 　　第一三共是一家为社会可持续发展做贡献的创新型全球医疗保健公司，致力于发现、开发和提供新的标准疗法，以提高世界各地患者的生活质量。第一三共专注制药行业120余年，凭借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远未得到满足的疾病患者研发新的治疗方法和创新药物。如欲了解更多信息，请访问www.daiichisankyo.com。 参考文献： 1.Ogitani Y, Aida T, Hagihara K, et al. DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res. 2016; 22(20):5097-108. 2.Hashimoto Y, Koyama K, Kamai Y, et al. A novel HER3-targeting antibody-drug conjugate, U3-1402, exhibits potent therapeutic efficacy through the delivery of cytotoxic payload by efficient internalization. Clin Cancer Res. 2019; 25(23):7151-61. 3.Okajima D, Yasuda S, Maejima T, et al. Datopotamab deruxtecan, a novel TROP2-directed antibody-drug conjugate, demonstrates potent antitumor activity by efficient drug delivery to tumor cells. Mol Cancer Ther. 2021; 20(12):2329-40. 4.Yamato M, Hasegawa J, Maejima T, et al. DS-7300a, a DNA topoisomerase I inhibitor, DXd-based antibody-drug conjugate targeting B7-H3, exerts potent antitumor activities in preclinical models. Mol Cancer Ther. 2022; 21(4):635-46. 5.Trastuzumab deruxtecan Investigator’s Brochure. Most current version. 6.Ogitani Y, Hagihara K, Oitate M, et al. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci. 2016; 107(7):1039-46. 7.Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020; 382(7):610-21. 8.Hattrup CL, Gendler SJ. Structure and function of the cell surface (tethered) mucins. Annu Rev Physiol. 2008; 70:431-57. 9.Gendler SJ, Spicer AP. Epithelial mucin genes. Annu Rev Physiol. 1995; 57:607-34. 10.Gendler SJ, Lancaster CA, Taylor-Papadimitriou J, et al. Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin. J Biol Chem. 1990; 265(25):15286-93. 11.Hanisch FG, Müller S. MUC1: the polymorphic appearance of a human mucin. Glycobiology. 2000; 10(5):439-49. 12.Nath S, Mukherjee P. MUC1: a multifaceted oncoprotein with a key role in cancer progression. Trends Mol Med. 2014; 20(6):332-42. 13.Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer. 2009; 9(12):874-85. 14.Lüttges J, Feyerabend B, Buchelt T, et al. The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreas. Am J Surg Pathol. 2002; 26(4):466-71. 15.Qing L, Li Q, Yang Y, et al. A prognosis marker MUC1 correlates with metabolism and drug resistance in bladder cancer: a bioinformatics research. BMC Urol. 2022; 22(1):114. 16.Fan XN, Karsten U, Goletz S, et al. Reactivity of a humanized antibody (hPankoMab) towards a tumor-related MUC1 epitope (TA-MUC1) with various human carcinomas. Pathol Res Pract. 2010; 206(8):585-9. 声明: 1.本材料不用于任何推广目的，相关信息亦不应作为治疗或使用建议。如有相关问题请咨询医疗卫生专业人士。 2.本文涉及未在中国获批的产品或适应症，第一三共不推荐任何未获批药品/适应症的使用。

September 15, 2025 7:00 am EDT First Breakthrough Therapy Designation for Daiichi Sankyo and Merck’s raludotatug deruxtecan based on phase 1 trial and REJOICE-Ovarian01 phase 2/3 trial Second Breakthrough Therapy Designation since the start of the Daiichi Sankyo and Merck collaboration Fifteenth Breakthrough Therapy Designation granted by FDA across the oncology portfolio of Daiichi Sankyo BASKING RIDGE, N.J. AND RAHWAY, N.J., September 15, 2025 – Raludotatug deruxtecan (R-DXd) has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancers expressing CDH6 who have received prior treatment with bevacizumab. Raludotatug deruxtecan is a specifically engineered, potential first-in-class CDH6 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. The FDA BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The medicine is required to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over currently available medicines. The FDA granted this BTD based on data from a phase 1 trial and the ongoing REJOICE-Ovarian01 phase 2/3 trial. A subgroup analysis of the phase 1 trial was presented at the 2023 European Society for Medical Oncology meeting (#ESMO23). Subsequent subgroup analyses of the phase 1 trial were presented at the 2024 Society for Gynecologic Oncology Annual Meeting on Women’s Cancer and the 2025 European Society for Medical Oncology Gynaecological Cancers Congress. This is the first BTD for raludotatug deruxtecan and represents the second BTD since the start of the Daiichi Sankyo and Merck collaboration. “Patients have limited treatment options once ovarian cancer becomes resistant to platinum-based chemotherapy, highlighting the urgent need for new medicines that can improve patient outcomes,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “The receipt of Breakthrough Therapy Designation represents an important step forward in our efforts to advance raludotatug deruxtecan as a novel medicine for patients with CDH6 expressing platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers previously treated with bevacizumab.” “The FDA’s Breakthrough Designation is a reflection of our commitment to advancing research for patients impacted by women’s cancers,” said Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories. “Raludotatug deruxtecan has the potential to one day become an important option for the treatment of patients with CDH6-expressing platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers previously treated with bevacizumab, and we are excited to share data from REJOICE-Ovarian01 with the scientific community at an upcoming medical meeting and to continue working closely with the FDA.” About the Phase 1 Trial The two-part, multicenter, open-label, first-in-human phase 1 trial is evaluating the safety and efficacy of investigational raludotatug deruxtecan in adult patients with advanced ovarian cancer previously treated with platinum-based chemotherapy and a taxane. Patients with renal cell carcinoma resistant or refractory to standard of care therapy were originally included, but that component of the study was discontinued. The primary objective of the first part of the study (dose escalation) was to assess the safety and tolerability of increasing doses of raludotatug deruxtecan to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE). The primary objective of the second part of the study (dose expansion) is to further evaluate the safety and efficacy of raludotatug deruxtecan in patients with advanced ovarian cancer and in patients with advanced renal cell carcinoma. The study will evaluate safety endpoints, including dose-limiting toxicities and adverse events and efficacy endpoints, including objective response rate (ORR), duration of response (DoR), disease control rate (DCR), clinical benefit rate, time to response and progression free survival (PFS). Pharmacokinetic and exploratory biomarker endpoints also will be assessed. The phase 1 trial enrolled 179 patients in Asia and North America. For more information, please visit ClinicalTrials.gov. About REJOICE-Ovarian01 REJOICE-Ovarian01 is a global, multicenter, randomized, open-label phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan in patients with platinum-resistant, high-grade ovarian primary peritoneal or fallopian tube cancer, with disease progression following at least one but no more than three prior systemic lines of therapy, including prior treatment with mirvetuximab soravtansine for those with documented high-folate receptor alpha expression. Maintenance therapy (e.g., bevacizumab, poly ADP-ribose polymerase [PARP] inhibitors) is considered part of the preceding line of therapy. The phase 2 part of REJOICE-Ovarian01 is assessing the safety and tolerability of three doses of raludotatug deruxtecan (4.8 mg/kg, 5.6 mg/kg, or 6.4 mg/kg) to identify the recommended dose for the phase 3 part of the trial. The primary endpoint of the phase 2 part of the trial is ORR as assessed by blinded independent central review (BICR). Secondary endpoints include ORR as assessed by investigator, DoR, PFS and DCR – all assessed by both BICR and investigator – and overall survival (OS). The phase 3 part of REJOICE-Ovarian01 is assessing the efficacy and safety of raludotatug deruxtecan at the selected dose (5.6 mg/kg) compared to investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, gemcitabine or topotecan). The dual primary endpoints of the phase 3 part of the trial are ORR and PFS as assessed by BICR. Secondary endpoints include PFS and ORR as assessed by investigator, DoR and DCR as assessed by both BICR and investigator, and OS. Pharmacokinetic and biomarker endpoints also will be assessed in both parts of the trial. REJOICE-Ovarian01 is expected to enroll approximately 710 patients across Asia, Europe, North America, and Oceania. For more information, please visit ClinicalTrials.gov. About Ovarian Cancer More than 324,000 women were diagnosed with ovarian cancer worldwide in 20221. The median overall survival for advanced ovarian cancer following recurrence can be as little as two years, with a five-year survival rate of 31.8% for those with distant stage disease.2,3 The introduction of targeted therapies has expanded treatment options and improved survival outcomes for some patients with ovarian cancer, but additional options are needed for patients with tumors that progress on available medicines4. Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens5. For patients who develop platinum-resistant ovarian cancer, defined as disease progression less than six months after completion of last platinum-based chemotherapy, prognosis is particularly poor and treatment options are limited.6,7 About CDH6 CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, including ovarian tumors.8 An estimated 65% of patients with ovarian cancer have tumors that express CDH6. In addition, CDH6 expression is observed more frequently in high-grade serous carcinomas.8,9 There is currently no CDH6 directed medicine approved for treatment of any cancer. About Raludotatug Deruxtecan Raludotatug deruxtecan is an investigational, potential first-in-class CDH6 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, raludotatug deruxtecan is comprised of a humanized anti-CDH6 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. About the Daiichi Sankyo and Merck Collaboration Daiichi Sankyo and Merck (known as MSD outside of the United States and Canada) 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 & Co., Inc., Rahway, N.J., USA will maintain exclusive rights. Merck & Co., Inc., Rahway, N.J., USA 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, N.J., 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. 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 www.merck.com/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. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2024, and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov). Media Contacts: Merck Media: Julie Cunningham (617) 519-6264 julie.cunningham@merck.com John Infanti (609) 500-4714 john.infanti@merk.com Investors: Peter Dannenbaum (732) 594-1579 peter.dannenbaum@merck.com Steven Graziano (732) 594-1583 steven.graziano@merck.com Daiichi Sankyo Global/US: Jennifer Brennan Daiichi Sankyo jennifer.brennan@daiichisankyo.com +1 (908) 900-3183 (mobile) Japan: Daiichi Sankyo Co., Ltd. DS-PR_jp@daiichisankyo.com Investor Relations Contact: DaiichiSankyoIR_jp@daiichisankyo.com References: