KEYMAKER-U01 Substudy 01I: A Phase 2, Randomized, Umbrella Study With Rolling Arms of Investigational Agents in Participants With Previously Treated Stage IV Squamous Non-small Cell Lung Cancer (NSCLC)

Researchers are looking for other ways to treat metastatic squamous non-small cell lung cancer (NSCLC). Squamous NSCLC is cancer that starts in squamous cells, which are flat cells that line the inside of the airways in the lungs. Metastatic means the cancer has spread to other parts of the body.
Standard treatment (usual treatment) for metastatic squamous NSCLC is immunotherapy with or without chemotherapy. Immunotherapy is a treatment that helps the immune system fight cancer. Chemotherapy is medicine that destroys cancer cells or stops them from growing. However, standard treatment may not work or may stop working to treat metastatic squamous NSCLC.
Researchers want to learn if study treatments that are antibody drug conjugates (ADCs) can treat metastatic squamous NSCLC that did not respond (get smaller or go away) to standard treatment. An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells.
The main goals of this study are to learn about:
* The cancer response to the study treatments compared to chemotherapy
* The safety of the study treatments and if people tolerate them
This study is one of the substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

开始日期2025-05-23

申办/合作机构

Merck Sharp & Dohme Corp.

[+1]

NCT06780085

/ Not yet recruiting临床2期

KEYMAKER-U01 Substudy 01H: A Phase 2, Randomized, Umbrella Study With Rolling Arms of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC)

Researchers are looking for new ways to treat metastatic nonsquamous non-small cell lung cancer (NSCLC) that has been treated before. Metastatic means the cancer has spread to other parts of the body. Nonsquamous means the cancer did not start in squamous cells, which are flat cells that line the inside of the lungs.
Standard treatment (usual treatment) for NSCLC is surgery, then immunotherapy with or without chemotherapy after surgery. Immunotherapy is a treatment that helps the immune system fight cancer. Chemotherapy is a medicine that works to destroy cancer cells or stop them from growing.
However, standard treatment may not work or may stop working for some people. Researchers want to know if 2 antibody drug conjugates (ADCs) can help treat metastatic nonsquamous NSCLC that did not respond (get smaller or go away) to treatment. An ADC attaches to specific targets on cancers cells and delivers treatment to destroy those cells.
Researchers will compare 2 different ADCs (the study treatments) to chemotherapy in this study. The goals of this study are to learn:
* About the safety of the study treatments and if people tolerate them
* How many people have the cancer respond to the study treatments

开始日期2025-05-14

申办/合作机构

Merck Sharp & Dohme Corp.

[+1]

NCT06780137

/ Recruiting临床1/2期

A Phase 1b/2 Open-Label Clinical Study to Evaluate the Safety and Efficacy of MK-6070 and Ifinatamab Deruxtecan (I-DXd) in Participants With Relapsed/Refractory Extensive-Stage Small Cell Lung Cancer

Researchers are looking for new ways to treat people with extensive-stage small cell lung cancer (SCLC) that has relapsed or is refractory. Gocatamig is a new type of immunotherapy that uses a person's immune system to find and destroy cancer cells. Ifinatamab deruxtecan (also known as I-DXd) is a drug which binds to specific targets on cancer cells and delivers treatment to destroy those cells. Researchers want to know if giving gocatamig and/or I-DXd can treat SCLC that did not respond or stopped responding to the first treatment.
The goals of this study are to learn:
* If gocatamig and I-DXd are safe and well tolerated
* If people who receive gocatamig and I-DXd have their SCLC get smaller or go away

开始日期2025-03-01

申办/合作机构

Merck Sharp & Dohme Corp.

[+1]

100 项与 Ifinatamab deruxtecan 相关的临床结果

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100 项与 Ifinatamab deruxtecan 相关的转化医学

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100 项与 Ifinatamab deruxtecan 相关的专利（医药）

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项与 Ifinatamab deruxtecan 相关的文献（医药）

2024-11-14·JOURNAL OF MEDICINAL CHEMISTRY

Evaluation of Double Self-Immolative Linker-Based Antibody–Drug Conjugate FDA022-BB05 with Enhanced Therapeutic Potential

Article

作者: Yin, Sicheng ; Liu, Shuangxi ; Zhang, Yifan ; Yang, Tong ; Zhang, Wenbo ; Shen, Keyu ; Xie, Qian ; Zhu, Shulei ; Gao, Bei ; Wu, Yinghan ; Song, Ruiwen ; Cao, Xuemei ; Qiu, Xuefei ; Cheng, Zhiyang ; Wang, Baoxia ; Zhao, Teng ; Xu, Jun ; Wu, Jingsong ; Li, Weinan ; Wang, Lei ; Guo, Qingsong ; Lu, Wei

Typical antibody-drug conjugates (ADCs) with valine-alanine linkage, often conjugated with the amino group in payloads, face challenges when interacting with hydroxyl group-containing payloads. Herein, we introduced a transformative Val-Ala-based double self-immolative linker-payload platform, reshaping ADCs by optimizing hydroxyl group-containing payload integration. Utilizing this platform, FDA022-BB05 was successfully conjugated with the hydroxyl group-containing payload DXd using trastuzumab (FDA022) as the monoclonal antibody (mAb). FDA022-BB05 demonstrated enhanced stability, effective cathepsin B sensitivity, reduced cell proliferation, increased bystander killing, and targeted delivery. Notably, acute toxicity evaluations in diverse preclinical models indicated favorable safety profiles and tolerability, with a broad therapeutic index in HER2-positive and -negative xenografts. Overall, these compelling findings support the promising therapeutic potential of FDA022-BB05, emphasizing the significance of diverse linker-payload platform strategies. This ADC is a valuable addition to targeted cancer therapy development, currently advancing through phase I clinical trials.

2024-10-01·BIOORGANIC CHEMISTRY

Novel antibody-drug conjugates based on DXd-ADC technology

Review

作者: Chen, Yuchen ; Ye, Qiang ; Hu, Xuefang ; Bai, Lan ; Shi, Jianyou ; Ren, Zhiwen ; Chen, Rong ; Hu, Yuan

In recent years, antibody-drug conjugate (ADC) technology, which uses monoclonal antibodies (mAbs) to specifically deliver effective cytotoxic payloads to tumor cells, has become a promising method of tumor targeted therapy. ADCs are a powerful class of biopharmaceuticals that link antibodies targeting specific antigens and small molecule drugs with potent cytotoxicity via a linker, thus enabling selective destruction of cancer cells while minimizing systemic toxicity. DXd is a topoisomerase I inhibitor that induces DNA damage leading to cell cycle arrest, making it an option for ADC payloads. The DXd-ADC technology, developed by Daiichi Sankyo, is a cutting-edge platform that produces a new generation of ADCs with improved therapeutic metrics and has shown significant therapeutic potential in various types of cancer. This review provides a comprehensive assessment of drugs developed with DXd-ADC technology, with a focus on mechanisms of action, pharmacokinetics studies, preclinical data, and clinical outcomes for DS-8201a, U3-1402, DS-1062a, DS-7300a, DS-6157a, and DS-6000a. By integrating existing data, we aim to provide valuable insights into the current therapeutic status and future prospects of these novel agents.

2024-10-01·MOLECULAR CANCER THERAPEUTICS

FZ-AD005, a Novel DLL3-Targeted Antibody–Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models

Article

作者: Lu, Wei ; Wu, Jinsong ; Shen, Jiafei ; Zhao, Teng ; Gao, Bei ; Yang, Tong ; Song, Ruiwen ; Guo, Qingsong ; Xie, Qian ; Lou, Sensen ; Zhang, Yifan ; Zhu, Shulei ; Li, Weinan ; Wang, Lei

Abstract:

Delta-like ligand 3 (DLL3) is overexpressed in small cell lung cancer (SCLC) and has been considered an attractive target for SCLC therapy. Rovalpituzumab tesirine was the first DLL3-targeted antibody–drug conjugate (ADC) to enter clinical studies. However, serious adverse events limited progress in the treatment of SCLC with rovalpituzumab tesirine. In this study, we developed a novel DLL3-targeted ADC, FZ-AD005, by using DXd with potent cytotoxicity and a relatively better safety profile to maximize the therapeutic index. FZ-AD005 was generated by a novel anti-DLL3 antibody, FZ-A038, and a valine–alanine (Val–Ala) dipeptide linker to conjugate DXd. Moreover, Fc-silencing technology was introduced in FZ-AD005 to avoid off-target toxicity mediated by FcγRs and showed negligible Fc-mediated effector functions in vitro. In preclinical evaluation, FZ-AD005 exhibited DLL3-specific binding and demonstrated efficient internalization, bystander killing, and excellent in vivo antitumor activities in cell line–derived xenograft and patient-derived xenograft models. FZ-AD005 was stable in circulation with acceptable pharmacokinetic profiles in cynomolgus monkeys. FZ-AD005 was well tolerated in rats and monkeys. The safety profile of FZ-AD005 was favorable, and the highest nonseverely toxic dose was 30 mg/kg in cynomolgus monkeys. In conclusion, FZ-AD005 has the potential to be a superior DLL3-targeted ADC with a wide therapeutic window and is expected to provide clinical benefits for the treatment of patients with SCLC.

259

项与 Ifinatamab deruxtecan 相关的新闻（医药）

2025-03-04

·第一三共中国

3期研究DG04显示优赫得®为HER2阳性转移性胃癌患者带来具有显著统计学差异和临床意义的总生存期改善

● 3期研究结果明确了第一三共和阿斯利康共同开发的优赫得®治疗二线转移性胃癌的疗效。 ● DESTINY-Gastric04期中研究显示优赫得®疗效更优，独立数据监察委员会建议研究结果提前揭盲。 ● 该研究结果将与全球监管机构分享。　　东京和新泽西州巴斯金里奇--（2025年3月3日）——3期研究DESTINY-Gastric04的总体阳性结果表明，与雷莫西尤单抗+紫杉醇相比，德曲妥珠单抗（商品名 - 优赫得®）为HER2阳性（IHC 3+或IHC 2+/ISH+）转移性胃或胃食管结合部（GEJ）腺癌患者带来具有显著统计学差异和临床意义的总生存期（OS）改善。　　期中分析中独立数据监察委员会观察到优赫得®疗效更优，建议提前揭盲。　　德曲妥珠单抗是一款采用独有技术设计的靶向HER2的DXd抗体偶联药物（ADC），该药物由第一三共研制，并由第一三共和阿斯利康共同开发和商业化。　　胃癌预后较差，尤其是晚期胃癌，其五年生存率为5%至10%1,2。在HER2阳性胃癌一线转移治疗中，使用含曲妥珠单抗的方案治疗出现疾病进展后，在DESTINY-Gastric04的研究结果出来之前，尚无靶向HER2的药物可在二线转移治疗中带来生存期获益3,4。　　根据随机2期研究DESTINY-Gastric01以及2项单臂2期研究DESTINY-Gastric02和DESTINY-Gastric06的研究结果，优赫得®目前已在超过65个国家/地区获得批准。DESTINY-Gastric04是优赫得®治疗HER2阳性晚期胃癌的首个3期研究。 Ken Takeshita 博士第一三共肿瘤研发部全球负责人　　优赫得®是首个且唯一在二线HER2阳性转移性胃癌患者随机3期研究中显示出生存期改善的HER2靶向药物，巩固了我们之前在其他早期胃癌研究中取得的研究成果。根据DESTINY-Gastric04的研究结果，我们将与全球监管机构合作，争取在优赫得®在尚未成为二线治疗选择的地区获得批准。　　DESTINY-Gastric04临床研究显示的安全性与优赫得®既往安全性一致。　　DESTINY-Gastric04数据将在即将召开的医学会议上公布，并与全球监管机构分享。　　　关于DESTINY-Gastric04　　　　　DESTINY-Gastric04是一项全球、随机、开放性三期研究，在使用含曲妥珠单抗方案治疗期间或治疗后出现疾病进展的HER2阳性（IHC 3+或IHC 2+/ISH+）转移性胃或GEJ腺癌患者中，评价德曲妥珠单抗（6.4 mg/kg）与雷莫西尤单抗和紫杉醇相比的疗效和安全性。　　主要终点为OS。次要终点包括研究者评估的无进展生存期、客观缓解率、缓解持续时间、疾病控制率和安全性。　　DESTINY-Gastric04在亚洲、欧洲、南美洲入组了494 例病人。欲了解有关该研究的更多信息，请访问ClinicalTrials.gov。　　　　关于HER2阳性胃癌　　　　　　胃癌是全球第五大常见癌症，也是全球第五大癌症相关死亡原因1,2。2022年新增胃癌确诊病例约100万2。胃癌的预后较差，尤其是晚期胃癌，五年生存率为5%至10%1,2。　　HER2是一种酪氨酸激酶受体促生长蛋白，在包括胃癌在内的多种肿瘤细胞表面均有表达4。大约五分之一的胃癌被认为是HER2阳性4,5。　　在HER2阳性胃癌一线转移治疗出现疾病进展后，之前尚无靶向HER2的药物可在二线随机临床试验中表明其生存获益3。　　　　　　关于优赫得®　　　　　　　　优赫得®是一款靶向HER2的ADC。采用第一三共独有的DXd-ADC技术设计，是第一三共肿瘤产品组合中的领先ADC产品，也是阿斯利康ADC科学平台中最先进的项目。德曲妥珠单抗由一种HER2单克隆抗体通过可裂解四肽连接子与若干拓扑异构酶I抑制剂有效载荷（依喜替康衍生物，DXd）连接组成。　　基于DESTINY-Breast03研究获得的结果，德曲妥珠单抗（5.4 mg/kg）已在全球超过75个国家/地区获得批准，用于治疗既往在转移阶段或在新辅助治疗期间或辅助治疗期间接受过一种抗HER2治疗方案且在治疗期间或完成治疗之后6个月内出现疾病复发的不可切除或转移性HER2阳性（[IHC]3+或[ISH]+）乳腺癌成人患者。　　基于DESTINY-Breast04研究获得的结果，德曲妥珠单抗（5.4 mg/kg）已在全球超过75个国家/地区获得批准，用于治疗既往在转移阶段接受过一种全身治疗，或在辅助化疗期间或完成辅助化疗后6个月内出现疾病复发的不可切除或转移性HER2低表达（IHC 1+或IHC 2+/ISH-）乳腺癌成人患者。　　基于DESTINY-Breast06研究获得的结果，德曲妥珠单抗（5.4 mg/kg）在美国获得批准，用于根据美国食品药品监督管理局（FDA）批准的检测方法确定在转移阶段接受一种或多种内分泌治疗后出现疾病进展的HR阳性、HER2低表达（IHC 1+或IHC 2+/ISH-）或HER2超低表达（IHC 0，伴膜染色）、不可切除或转移性乳腺癌成人患者。　　基于DESTINY-Lung02和/或DESTINY-Lung05研究获得的结果，德曲妥珠单抗（5.4 mg/kg）已在全球超过50个国家/地区获得批准，用于治疗通过当地或地区批准的检测方法检出肿瘤存在HER2（ERBB2）激活突变且既往接受过一种全身治疗的不可切除或转移性非小细胞肺癌（NSCLC）成人患者。该适应症能否在中国和美国完全批准取决于是否可通过确证性研究验证和确定可提供临床获益。　　基于DESTINY-Gastric01、DESTINY-Gastric02和/或DESTINY-Gastric06研究获得的结果，德曲妥珠单抗（6.4 mg/kg）已在全球超过65个国家/地区获批，用于治疗既往接受过基于曲妥珠单抗的治疗方案的局部晚期或转移性HER2阳性（IHC 3+或IHC 2+/ISH+）胃或GEJ腺癌成人患者。中国于2024年8月基于DG06研究获得附条件批准，用于治疗既往接受过两种或两种以上治疗方案的局部晚期或转移性HER2阳性成人胃或胃食管结合部腺癌患者，该适应症在中国的完全批准取决于能否通过确证性研究验证和确定可提供临床获益。　　基于DESTINY-PanTumor02、DESTINY-Lung01和DESTINY-CRC02研究的疗效结果，德曲妥珠单抗（5.4 mg/kg）已在巴西、以色列、俄罗斯和美国获批，用于治疗既往接受过全身治疗且无满意替代治疗选择的不可切除或转移性HER2阳性（IHC 3+）实体瘤成人患者。该适应症能否完全批准取决于是否可通过确证性研究验证和确定可提供临床获益。　　　关于优赫得®临床开发计划　　　　　旨在评价德曲妥珠单抗单药治疗多种HER2靶向癌症的疗效和安全性的全面临床研发计划正在全球范围内进行。联合免疫治疗等其他抗肿瘤治疗的研究也在进行中。　　关于第一三共和阿斯利康的合作　　　　第一三共与阿斯利康分别于2019年3月和2020年7月达成全球合作，共同开发和商业化优赫得®和达卓优® (DATROWAY®)，在日本市场第一三共拥有各款ADC产品的独家权益。第一三共负责优赫得®和达卓优® 的生产和供应。　　　关于第一三共ADC产品组合　　　　　第一三共的ADC产品组合包括7款处于临床开发阶段的ADC，这些ADC基于第一三共开发的两个ADC技术平台。　　目前临床开发进展最为领先的ADC平台当属第一三共的DXd ADC技术平台，每款ADC由单克隆抗体通过可裂解四肽连接子与多个拓扑异构酶I抑制剂有效载荷（一种依喜替康衍生物，DXd）连接组成。DXd ADC产品组合目前包括靶向HER2的ADC德曲妥珠单抗和靶向TROP2的ADC DATROWAY，上述两款产品目前正由第一三共与阿斯利康共同开发并在全球范围内商业化。Patritumab deruxtecan（HER3-DXd，靶向HER3的ADC）、ifinatamab deruxtecan（I-DXd，靶向B7-H3的ADC）、raludotatug deruxtecan（R-DXd，靶向CDH6的ADC）目前正由第一三共与Merck & Co., Inc（Rahway, NJ, USA）共同开发并在全球范围内商业化。DS-3939是一款靶向TA-MUC1的ADC，目前正由第一三共开发。　　第一三共的第二个ADC平台由单克隆抗体与改良吡咯并苯并二氮杂卓 (PBD) 有效载荷连接组成。DS-9606是一款靶向CLDN6的PBD ADC，是计划利用该平台并处于临床开发阶段的几种ADC中的第一种ADC。　　I-DXd、HER3-DXd、R-DXd、DS-3939和DS-9606均为在研药物，尚未在任何国家/地区获批用于任何适应症。安全性和疗效尚未确定。　　　　　　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.Casamayor M, et al. Ecancermedicalscience. 2018;12:883. 2.Globocan 2022. Stomach Cancer. Accessed December 2024. 3.Mitani S, et al. Cancers. 2020;12(2):400. 4.Abrahao-Machado LF, et al. World J Gastroenterol. 2016;22(19):4619-25. 5.Iqbal N, et al. Mol Biol Int. 2014:852748. 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。 3.截止获批当日，根据ClinicalTrials.gov数据库，DB06适应症为全球市场唯一获批适应症。

临床结果抗体药物偶联物临床3期

2025-03-03

·PipelineReview

ENHERTU® Demonstrated Statistically Significant and Clinically Meaningful Improvement in Overall Survival in Patients with HER2 Positive Metastatic Gastric Cancer at Interim Analysis of DESTINY-Gastric04 Phase 3 Trial

TOKYO, Japan & BASKING RIDGE, NJ, USAI March 03, 2025 I Positive topline results from the DESTINY-Gastric04 phase 3 trial showed ENHERTU ® (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of overall survival (OS) compared to ramucirumab and paclitaxel in patients with second-line HER2 positive (IHC 3+ or IHC 2+/ISH+) unresectable and/or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. At a planned interim analysis, the Independent Data Monitoring Committee recommended unblinding the trial based on the superior efficacy of ENHERTU. 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). Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is 5% to 10%. 1,2 Following disease progression in the first-line metastatic setting of HER2 positive gastric cancer, there historically have been no HER2 directed medicines that have demonstrated a survival benefit in the second-line metastatic setting in a randomized clinical trial. 3 ENHERTU is currently approved in more than 65 countries based on DESTINY-Gastric01 , a randomized phase 2 trial, and DESTINY-Gastric02 and DESTINY-Gastric06 , two single-arm phase 2 trials. DESTINY-Gastric04 is the first phase 3 trial of ENHERTU in HER2 positive advanced gastric cancer. “ENHERTU is the first HER2 directed medicine to demonstrate an improvement in overall survival in a randomized phase 3 trial in the second-line metastatic setting of patients with HER2 positive gastric cancer, reinforcing previous findings seen in our other earlier phase gastric cancer trials,” said Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo. “With these DESTINY-Gastric04 results, we will work with global regulatory authorities to seek approval in regions where ENHERTU is not currently indicated as a second-line option, as well as work to secure full approval in regions where ENHERTU is conditionally approved.” “We are committed to advancing the care of patients with metastatic gastric cancer and continuing to understand the role of ENHERTU in earlier lines of treatment,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “The results of DESTINY-Gastric04 show that second-line treatment with ENHERTU can extend survival compared with a chemotherapy-based regimen and should be considered for all eligible patients with HER2 positive metastatic gastric cancer.” The safety profile seen in DESTINY-Gastric04 is consistent with the established safety profile of ENHERTU. Data from DESTINY-Gastric04 will be presented at an upcoming medical meeting and shared with global regulatory authorities. About DESTINY-Gastric04 DESTINY-Gastric04 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (6.4 mg/kg) versus ramucirumab and paclitaxel in patients with HER2 positive (IHC 3+ or IHC 2+/ISH+) unresectable and/or metastatic gastric or GEJ adenocarcinoma with disease progression on or after a trastuzumab-containing regimen. The primary endpoint is OS. Secondary endpoints include investigator-assessed progression-free survival, objective response rate, duration of response, disease control rate and safety. DESTINY-Gastric04 enrolled 494 patients in Asia, Europe and South America. For more information about the trial, visit ClinicalTrials.gov . About HER2 Positive Gastric Cancer Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth leading cause of cancer-related death. 1,2 Approximately one million cases of gastric cancer were diagnosed in 2022. 2 Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is 5% to 10%. 1,2 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including gastric cancer. 4 Approximately one in five gastric cancers are considered HER2 positive. 4,5 Following disease progression in the first-line metastatic setting of HER2 positive gastric cancer, there historically have been no HER2 directed medicines that have demonstrated a survival benefit in the second-line metastatic setting in a randomized clinical trial. 3 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 75 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 75 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 the U.S. for the treatment of adult patients with unresectable or metastatic HR positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA approved test, that have 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 50 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 65 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 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 monotherapy across multiple HER2 targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway. 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. ENHERTU U.S. Important Safety Information Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:Unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen either: 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 Casamayor M, et al. Ecancermedicalscience. 2018;12:883. 2 Globocan 2022. Stomach Cancer. Accessed December 2024. 3 Mitani S, et al. Cancers. 2020;12(2):400. 4 Abrahao-Machado LF, et al. World J Gastroenterol. 2016;22(19):4619-25. 5 Iqbal N, et al. Mol Biol Int. 2014:852748. SOURCE: Daiichi Sankyo

临床结果上市批准临床3期免疫疗法抗体药物偶联物

2025-02-24

·金赛药业

金赛药业携肿瘤领域高度差异化的双靶ADC管线亮相ADC2025

2月20日，金赛药业免疫及肿瘤领域新药研发执行副总裁徐立忠博士携GenSci139和GenSci143创新管线亮相苏州第六届ADC药物开发大会（简称ADC2025），与国内权威专家学者共话ADC发展的新未来。此次，金赛药业携带的两个创新管线项目皆为高度差异化的双靶ADC，分别用于治疗转移性去势抵抗性前列腺癌（mCRPC）及多种实体瘤。金赛药业免疫及肿瘤领域新药研发执行副总裁徐立忠博士主题分享本次大会，徐立忠博士发表了题为“靶向癌症治疗的双特异性ADC”的主题演讲，并主持了“ADC药物前沿进展”圆桌讨论。国产ADC药物正迅速进入差异化开发的2.0时代。作为研发管线的创新源头，药物技术平台的重要性日益凸显。本次大会金赛药业着重展示了其自主研发的基于拓扑异构酶抑制剂的ADC药物技术平台。徐立忠博士（左一）主持圆桌讨论徐立忠博士在发言中强调：“此次我们基于金赛自主研发的ADC药物技术平台，携两款具有差异化优势的双靶ADC候选药物及创新技术成果，向与会专家及合作伙伴展示了研发进展。依托该平台优异的稳定性、显著的旁观者效应及宽广的安全窗等优势特性，我们期待与全球头部医药企业建立深度战略合作，加速推进ADC药物在研发管线的临床转化效率与商业化进程，最终实现创新成果的高效转化，为全球患者提供更具突破性的治疗选择。” 在此前举行的中国顶尖生命科学合作论坛China Bio及国际权威ADC领域峰会World ADC 2024上，金赛药业自主研发的GenSci143与GenSci139作为核心管线项目公开披露，凭借其创新分子设计及针对实体瘤治疗的突破潜力，两款候选药物引发了全球ADC研发领域的高度关注。根据最新规划，GenSci143与GenSci139将于2025年第四季度同步启动IND申报，重点探索其在去势抵抗性前列腺癌、非小细胞肺癌、尿路上皮癌、乳腺癌及卵巢癌等五大高发实体瘤中的治疗价值，以解决当前临床未被满足的重大需求。在聚焦肿瘤创新治疗的同时，金赛药业已构建起围绕内分泌代谢、女性健康、免疫、肿瘤等重点领域研发战略纵深布局，多款临床前候选药物展现出First-in-Class与Best-in-Class的巨大潜质，特别是在自身免疫疾病调控通路及代谢稳态重构机制等前沿方向凸显源头创新实力；此外，金赛研发体系全面接轨全球最高研发标准体系（ICH-Q系列），通过AI驱动的分子设计平台与智能化CMC开发系统，系统化推进创新药物研发。以突破性技术平台为根基、以临床价值为导向，金赛药业正持续打造具有全球竞争力的差异化管线矩阵，为满足全球患者亟待解决的临床需求提供创新解决方案。徐立忠博士与参会者讨论关于GenSci143：高度差异化的B7-H3 x PSMA双靶ADC 前列腺癌（PCa）是全球男性中最常见的癌症类型。当患者进展到去势抵抗性前列腺癌（CRPC）时，治疗选择变得非常有限，这突显出转移性去势抵抗性前列腺癌（mCRPC）中显著未满足的临床需求。B7-H3和PSMA是肿瘤相关的抗原，在PCa中高度表达，用双靶ADC同时靶向这两种抗原是一种新兴的治疗策略，具有治疗mCRPC的潜力。 GenSci143是一种创新的双特异性抗体药物偶联物（ADC），能够同时靶向B7-H3和PSMA。它由针对B7-H3和PSMA的双特异性抗体、稳定但可裂解的连接器，以及作为有效载荷的强效拓扑异构酶1抑制剂组成。 GenSci143作为一种新型靶向前列腺癌治疗的药物，目前正在进行临床前研究。在人前列腺癌的异种移植（CDX）模型中，GenSci143能够有效诱导具有不同B7-H3和PSMA表达水平的肿瘤消退，并且与DS-7300和ARX517竞品相比，展现出了更优越的抗肿瘤效果。此外，GenSci143在食蟹猴中显示出了良好的药代动力学特性，并且耐受性良好。关于GenSci139：高度差异化的EGFR x HER2双靶ADC Enhertu®/DS-8201作为一种靶向HER2的ADC，已广泛用于治疗多种肿瘤类型，包括HER2阳性和HER2低表达乳腺癌、HER2突变非小细胞肺癌、HER2阳性胃癌等。尽管Enhertu作为一种突破性疗法取得了很大的成功，但在 HER2 低表达和产生继发耐药的患者中，仍有大量未满足的临床需求。双重靶向EGFR 和 HER2有望解决这些问题，因为两者都是致癌驱动基因并且在肿瘤中广泛共表达。为此，金赛药业开发了 GenSci139，一种EGFR x HER2 双靶ADC，它具有高度稳定但可裂解的连接子和强效的拓扑异构酶1抑制剂作为有效载荷。相比于DS-8201，GenSci139具有更优的体外血浆稳定性、更强的肿瘤细胞结合和内化活性，并对肿瘤细胞具有强效的直接细胞杀伤和旁观者杀伤作用。在多个小鼠 CDX 模型中，GenSci139表现出显著优于 DS-8201的体内抗肿瘤效果。这些数据表明GenSci139在多种肿瘤类型中具有较大的治疗潜力，包括尿路上皮癌、肺癌、胃癌、结直肠癌、卵巢癌和乳腺癌等。 END

抗体药物偶联物临床申请

100 项与 Ifinatamab deruxtecan 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
转移性食管鳞状细胞癌	临床3期	-	Daiichi Sankyo Co., Ltd.	2025-02-28
食管鳞状细胞癌	临床3期	美国	Daiichi Sankyo, Inc.	2025-02-19
食管鳞状细胞癌	临床3期	中国	Daiichi Sankyo, Inc.	2025-02-19
食管鳞状细胞癌	临床3期	日本	Daiichi Sankyo, Inc.	2025-02-19
食管鳞状细胞癌	临床3期	比利时	Daiichi Sankyo, Inc.	2025-02-19
食管鳞状细胞癌	临床3期	丹麦	Daiichi Sankyo, Inc.	2025-02-19
食管鳞状细胞癌	临床3期	法国	Daiichi Sankyo, Inc.	2025-02-19
食管鳞状细胞癌	临床3期	德国	Daiichi Sankyo, Inc.	2025-02-19
食管鳞状细胞癌	临床3期	意大利	Daiichi Sankyo, Inc.	2025-02-19
食管鳞状细胞癌	临床3期	荷兰	Daiichi Sankyo, Inc.	2025-02-19

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05280470 (ESMO2024)	临床2期	广泛期小细胞肺癌	-	Ifinatamab deruxtecan 8 mg/kg	鬱繭蓋獵簾簾鑰積願獵(襯餘壓窪遞壓製構衊繭) = 35% had Grade ≥3 TEAEs (47% in pts without BL BM) 鑰齋窪網餘鏇壓壓艱壓 (窪鏇鹹衊鹹襯齋壓鬱壓 ) 更多	-	2024-09-14
NCT05280470 (ESMO2024)	临床2期	广泛期小细胞肺癌	-	Ifinatamab deruxtecan 12 mg/kg		-	2024-09-14
NCT06362252 (IDeate-Lung03, ESMO2024)	临床1/2期	广泛期小细胞肺癌一线 \| 维持 B7 homolog 3 (B7-H3)	149	I-DXd 12 mg/kg + atezo maintenance	襯齋願獵獵鑰簾構鑰範(遞鹽積蓋壓範積衊願顧) = 醖範鹹鑰顧繭糧夢選簾構齋積衊壓糧憲鑰壓築 (網膚窪壓選艱憲積顧夢 ) 更多	积极	2024-09-14
NCT05280470 \| NCT04145622 (IDeate-L01, WCLC2024) 人工标引	临床1/2期	广泛期小细胞肺癌	256	I-DXd 8 mg/kg	鏇簾製餘蓋淵膚壓糧簾(淵鏇廠艱選衊蓋醖獵窪) = 齋窪築鏇膚鬱餘獵襯膚餘積夢齋網觸繭衊觸壓 (遞製範夢鹹壓衊顧顧積 ) 更多	积极	2024-09-08
NCT05280470 (IDeate-Lung01, BusinessWire) 人工标引	临床2期	广泛期小细胞肺癌	88	Ifinatamab deruxtecan 12 mg/kg	積選齋衊構膚鹽積築遞(衊選鏇艱顧鹽顧壓艱鏇) = 憲艱鬱顧鹹艱膚簾廠壓觸艱壓鏇餘壓艱鹹壓顧 (構窪簾艱鏇餘廠膚繭鏇, 38.7 ~ 70.2) 更多	积极	2024-09-07
NCT05280470 (IDeate-Lung01, BusinessWire) 人工标引	临床2期	广泛期小细胞肺癌	88	Ifinatamab deruxtecan 8 mg/kg	積選齋衊構膚鹽積築遞(衊選鏇艱顧鹽顧壓艱鏇) = 觸製範膚餘醖觸積醖願觸艱壓鏇餘壓艱鹹壓顧 (構窪簾艱鏇餘廠膚繭鏇, 14.3 ~ 41.1) 更多	积极	2024-09-07
NCT04145622 (ESMO 12023 \| ESMO 22023) 人工标引	临床1/2期	实体瘤	-	Ifinatamab deruxtecan (CRPC)	範艱簾艱積醖餘獵製蓋(淵憲構觸繭衊鑰觸簾衊) = 網憲鏇壓蓋繭範淵簾餘網顧網範鹹鹽觸廠遞艱 (憲衊積願願夢網網膚餘 ) 更多	积极	2023-10-23
NCT04145622 (ESMO 12023 \| ESMO 22023) 人工标引	临床1/2期	实体瘤	-	Ifinatamab deruxtecan (ESCC)	範艱簾艱積醖餘獵製蓋(淵憲構觸繭衊鑰觸簾衊) = 蓋獵觸鏇製膚夢網鏇淵網顧網範鹹鹽觸廠遞艱 (憲衊積願願夢網網膚餘 ) 更多	积极	2023-10-23
NCT04145622 (WCLC2023) 人工标引	临床1/2期	小细胞肺癌 B7-H3	21	I-DXd	衊齋繭廠網夢夢遞鏇夢(網膚蓋窪鬱選鹽壓糧鬱) = 選鹽遞範餘齋夢壓鬱淵觸構窪鑰選醖築鏇網製 (遞蓋簾顧壓鏇構繭憲築 ) 更多	积极	2023-09-10
NCT04145622 (ESMO2022) 人工标引	临床1/2期	HR阳性/HER2低表达实体瘤 CD276 Overexpression	127	DS-7300 (Total)	窪壓製憲糧鏇鑰憲鏇齋(鑰襯膚醖襯襯製齋顧鹽) = 廠鹹鏇餘積糧網艱齋鬱簾鑰齋襯餘觸製齋襯繭 (衊糧鑰蓋鏇憲積糧築鬱 ) 更多	积极	2022-09-10
NCT04145622 (ESMO2022) 人工标引	临床1/2期	HR阳性/HER2低表达实体瘤 CD276 Overexpression	127	DS-7300 (SCLC)	窪壓製憲糧鏇鑰憲鏇齋(鑰襯膚醖襯襯製齋顧鹽) = 蓋蓋壓醖憲膚壓糧廠網簾鑰齋襯餘觸製齋襯繭 (衊糧鑰蓋鏇憲積糧築鬱 ) 更多	积极	2022-09-10
NCT04145622 (ASCO_GU2022) 人工标引	临床1/2期	转移性去势抵抗性前列腺癌	29	DS-7300	醖鏇襯遞繭齋鬱積蓋餘(鹽壓蓋積蓋衊願齋觸築) = 夢鬱窪糧餘選製網繭簾衊憲範遞觸鏇廠繭觸鹹 (鏇衊艱簾鏇鏇淵築網鏇 ) 更多	积极	2022-02-16
NCT04145622 (ESMO2021) 人工标引	临床1/2期	HR阳性/HER2低表达实体瘤 B7-H3 expression	56	DS-7300	遞顧積築蓋蓋願範夢遞(鑰衊膚醖壓艱築衊鬱蓋) = 膚醖簾積壓獵廠膚願願構膚淵糧顧夢憲觸憲醖 (壓製積鹹醖鬱淵顧鏇積 ) 更多	积极	2021-09-17