A Phase 3, Multicenter, Randomized, Open-label Study of Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Advanced or Metastatic Esophageal Squamous Cell Carcinoma (ESCC) (IDeate-Esophageal01)

This study is designed to assess the efficacy and safety of ifinatamab deruxtecan (I-DXd) in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have experienced disease progression following treatment with a platinum-containing systemic therapy and an immune checkpoint inhibitor (ICI) compared with investigator's choice of chemotherapy (ICC).

开始日期2025-02-28

申办/合作机构

Daiichi Sankyo Co., Ltd.

[+1]

CTR20242805 / Recruiting临床3期

一项在复发性小细胞肺癌（SCLC）受试者中比较Ifinatamab Deruxtecan（I-DXd）（一种B7-H3抗体偶联药物（ADC））与医生所选治疗（TPC）的多中心、随机、开放性、3期研究（IDeate Lung02）

本试验旨在进一步评估比较I-DXd与医生所选治疗在复发性SCLC受试者中的有效性和安全性。本研究的主要目的是评估I-DXd治疗与医生所选疗法治疗相比，是否可改善复发性SCLC受试者的客观缓解率（ORR）并延长总生存期（OS）。次要目的是进一步评价I-DXd的有效性和安全性，卫生经济学和结果研究(包括患者自报结果)，I-DXd的免疫原性，B7-H3 蛋白的表达，和表征I-DXd的PK。

开始日期2024-09-02

申办/合作机构

Daiichi Sankyo Propharma Co., Ltd.

[+2]

NCT06362252 / Recruiting临床1/2期

A Phase 1b/2, Multicenter, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody-Drug Conjugate (ADC), in Combination With Atezolizumab With or Without Carboplatin as First-line Induction or Maintenance, in Subjects With Extensive-stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung03)

This study is designed to evaluate the safety and efficacy of ifinatamab deruxtecan (I-DXd) in combination with immune checkpoint inhibitor (ICI) atezolizumab with or without carboplatin in participants with extensive stage-small cell lung cancer (ES-SCLC) in the first-line (1L) setting.

开始日期2024-07-22

申办/合作机构

Daiichi Sankyo Co., Ltd.

[+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）

2024-11-04·MOLECULAR CANCER THERAPEUTICS

A DXd/TLR7-Agonist Dual-Conjugate Anti-HER2 ADC Exerts Robust Antitumor Activity Through Tumor Cell Killing and Immune Activation

Article

作者: Geng, Meiyu ; Xie, Zuoquan ; Meng, Tao ; Wang, Xiyuan ; Li, Han ; Yue, Hangtian ; Li, Xiyuan ; Yang, Biyu ; Ma, Lanping ; Zeng, Qingzhong ; Xu, Hui ; Zhang, Deqiang

Abstract:

The emergence of trastuzumab deruxtecan (T-DXd), a new-generation antibody–drug conjugate (ADC), has profoundly altered the therapeutic paradigm for HER2-positive solid tumors, demonstrating remarkable clinical benefits. However, the combined outcomes of T-DXd with immunotherapy agents remain ambiguous. In this study, we introduce Tras-DXd-MTL1, an innovative HER2 targeting ADC that integrates the topoisomerase inhibitor DXd and a toll like receptor 7 (TLR7) agonist MTT5, linked to trastuzumab via a GGFG tetrapeptide linker. Mechanistically, Tras-DXd-MTL1 retains the DNA-damaging and cell-killing properties of topoisomerase inhibitors while simultaneously enhancing the immune response within the tumor microenvironment. This is achieved by promoting immune cell infiltration and activating dendritic cells and CD8+T cells via MTT5. In vivo evaluation of Tras-DXd-MTL1’s antitumor potency revealed a notably superior performance compared with the T-DXd (Tras-DXd) or Tras-MTL1 in immunocompetent mice with trastuzumab-resistant EMT6-HER2 tumor and immunodeficient mice with JIMT-1 tumor. This improved efficacy is primarily attributed to its dual functions of immune stimulation and cytotoxicity. Our findings highlight the potential of incorporating immunostimulatory agents into ADC design to potentiate antitumor effects and establish durable immune memory, thereby reducing tumor recurrence risks. Therefore, our study offers a novel strategy for the design of immune-activating ADCs and provides a potential approach for targeting solid tumors with different levels of HER2 expression.

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 ; Hu, Yuan ; Chen, Rong

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.

2024-06-02·EXPERT OPINION ON BIOLOGICAL THERAPY

Progress in second-line antibody therapies for advanced esophageal squamous cell carcinoma

Review

作者: Yamamoto, Shun ; Ogura, Nozomu ; Kato, Ken

INTRODUCTION:

The prognosis of advanced esophageal squamous cell carcinoma (ESCC) is poor. Although cytotoxic drugs have been widely used in advanced ESCC, several antibody agents have recently been reported to be effective.

AREAS COVERED:

Nivolumab and pembrolizumab are anti-PD-1 antibodies that improve immunosuppression by binding to programmed death-1 (PD-1), leading to an antitumor effect. Randomized phase III trials have found these immune checkpoint inhibitors (ICIs) to be effective as second-line treatment. ATTRACTION-3, which compared nivolumab monotherapy with taxane monotherapy in patients with previously treated advanced ESCC, reported prolonged overall survival in the nivolumab group. KEYNOTE-181 found that overall survival was longer in patients with PD-L1-positive ESCC who received second-line treatment with pembrolizumab than in those who received chemotherapy. Sym004 and amivantamab are antibodies that target the epidermal growth factor receptor and have demonstrated efficacy in the treatment of other tumors in recent phase I studies. Furthermore, clinical trials on antibody-drug conjugates such as enfortumab vedotin and DS-7300 for solid tumors are currently ongoing.

EXPERT OPINION:

The standard first-line treatments for patients with advanced ESCC contain ICIs. Therefore, drugs with different mechanisms of action that can overcome resistance to ICIs are needed as second-line or later-line treatments to improve clinical outcomes in these patients.

268

项与 Ifinatamab deruxtecan 相关的新闻（医药）

2024-12-24

·PipelineReview

Datopotamab Deruxtecan Application in the EU for Patients with Advanced Nonsquamous Non-Small Cell Lung Cancer Voluntarily Withdrawn

TOKYO, Japan & MUNICH, Germany I December 24, 2024 I Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/Nasdaq: AZN) have voluntarily withdrawn the marketing authorization application (MAA) in the EU for datopotamab deruxtecan (Dato-DXd) for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) based on the TROPION-Lung01 phase 3 trial. The decision to withdraw the MAA was informed by feedback from the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA). Daiichi Sankyo and AstraZeneca will continue to work to bring datopotamab deruxtecan to patients with lung cancer in the EU who can benefit and are committed to unlocking the potential of this medicine in lung cancer through our robust clinical development program which includes seven pivotal trials in various lung cancer settings. Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and AstraZeneca. Daiichi Sankyo and AstraZeneca’s application in the EU for datopotamab deruxtecan for the treatment of hormone receptor (HR) positive, HER2 negative metastatic breast cancer based on the TROPION-Breast01 phase 3 trial remains under review. About TROPION-Lung01 TROPION-Lung01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan versus docetaxel in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with an approved targeted therapy and platinum-based chemotherapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The dual primary endpoints of TROPION-Lung01 are progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS). Key secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, time to response, and disease control rate as assessed by both BICR and investigator, and safety. TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . Primary PFS results and interim OS results from TROPION-Lung01 were presented at the 2023 ESMO (#ESMO23) Congress. Final OS results were presented at IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC24) and simultaneously published in the Journal of Clinical Oncology in September 2024. About Advanced Non-Small Cell Lung Cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. 1 In Europe, nearly 500,000 lung cancer cases were diagnosed in 2022. 1 Lung cancer is broadly split into small or non-small cell lung cancer, the latter accounting for about 80% of cases. 2 While immunotherapy and targeted therapies have improved outcomes in the first-line setting, most patients eventually experience disease progression and receive chemotherapy. 3,4,5 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects. 3,4,5 TROP2 is a protein broadly expressed in the majority of NSCLC tumors. 6 There is currently no TROP2 directed ADC approved for the treatment of lung cancer. 7,8 About Datopotamab Deruxtecan (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 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. Additional regulatory submissions in breast cancer are under review in China, Japan, the U.S. and other regions. Datopotamab deruxtecan has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFR-mutated) NSCLC with disease progression on or after treatment with an EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy. Daiichi Sankyo and AstraZeneca have submitted a Biologics License Application for datopotamab deruxtecan for this potential indication. About the Datopotamab Deruxtecan Clinical Development Program 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 low or 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. 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 datopotamab deruxtecan 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. 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 datopotamab deruxtecan, 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. 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. 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 World Health Organization. Global Cancer Observatory: Lung. Accessed December 2024. 2 American Cancer Society. Key Statistics for Lung Cancer . Accessed December 2024. 3 Chen R, et al. J Hematol Oncol . 2020:13(1):58. 4 Majeed U, et al. J Hematol Oncol . 2021;14(1):108. 5 Pircher A, et al. Anticancer Research . 2020;70(5):287-294. 6 Mito R, et al. Pathol Int . 2020;70(5):287-294. 7 American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer . Accessed December 2024. 8 Rodríguez-Abreau D, et al. Ann Onc . 2021 Jul;32(7): 881-895. SOURCE: Daiichi Sankyo

临床3期临床结果上市批准引进/卖出突破性疗法

2024-12-18

·肿瘤界

盘点2024丨黄鼎智教授：2024年度小细胞肺癌治疗研究进展

点击蓝字关注我们李梦洁，黄鼎智（天津医科大学肿瘤医院　肺部肿瘤内科　国家恶性肿瘤临床医学研究中心　天津市恶性肿瘤临床医学研究中心　天津市肿瘤防治重点实验室，天津　300060）基金项目：国家自然科学基金项目（82172635）；天津市医学重点学科（专科）建设项目（TJYXZDXK-010A）通信作者：黄鼎智　E-mail ：dingzhih72@163.com 通信作者黄鼎智教授主任医师，肿瘤学博士，博士生导师天津医科大学肿瘤医院副院长天津市抗癌协会秘书长天津市抗癌协会肺癌专委会候任主任委员中国抗癌协会(CACA)肿瘤临床研究管理学专委会副主委中国临床肿瘤学会(CSCO)老年肿瘤防治专业委员会常委中国抗癌协会(CACA)肺癌专业委员会委员中国抗癌协会(CACA)肿瘤靶向治疗专业委员会委员中国抗癌协会(CACA)肿瘤精准治疗专业委员会委员中国临床肿瘤学会(CSCO)非小细胞肺癌专业委员会委员国家肿瘤质控中心肺癌质控专家委员会委员中国医疗保健国际交流促进会肿瘤内科分会常委《中华肿瘤杂志》《中国肿瘤临床》编委主持国家科技重大专项-重大新药创制专项子课题1项，国自然面上2项，市科委、教委各1项。获天津市科技进步一、二、三等奖各一项。【摘要】小细胞肺癌（small cell lung cancer，SCLC）恶性程度高、预后极差。局限期小细胞肺癌（limited stage-small cell lung cancer，LS-SCLC）同步放化疗是基石治疗，ADRIATIC研究重塑LS-SCLC治疗新格局。同步放化疗后免疫巩固成为LS-SCLC治疗新标准，且初步结果提示，ADRIATIC模式优于免疫同步放化疗后免疫巩固。广泛期SCLC（extensive stage-small cell lung cancer，ES-SCLC）免疫检查点抑制剂联合化疗一线治疗的临床获益达到瓶颈，最新研究结果提示，联合抗血管生成治疗的四药方案为ES-SCLC提供了一种高效的治疗模式。ES-SCLC一线化疗联合免疫序贯胸部放射治疗可一定程度延缓一线治疗进展、提高免疫治疗的获益人群，但仍需探索最佳联合治疗模式。Delta样配体3（Delta-like ligand 3，DLL3）作为SCLC热门治疗靶点，以DLL3为靶点的双特异性抗体tarlatamab更新研究随访结果提示，长期疗效及耐受性良好，且以tarlatamab为基础的联合治疗方案逐渐向前线探索。共刺激分子B7H3和滋养层细胞表面抗原2作为抗体药物偶联物新靶点初步疗效展现其治疗潜力，但仍需扩大人群以及面临Ⅲ期临床试验的挑战。【关键词】小细胞肺癌；联合治疗；靶向治疗；抗体药物偶联物小细胞肺癌（small cell lung cancer，SCLC）是一种高侵袭性的肺癌，占肺癌总发病率的15%～20%，根据确诊时是否发生远处转移可分为局限期小细胞肺癌（limited stage-small cell lung cancer，LS-SCLC）和广泛期小细胞肺癌（extensive stage-small cell lung cancer，ES-SCLC）[1]。SCLC生长迅速、恶性程度高，易出现转移，近70%的SCLC患者确诊时已出现远处转移，而被诊断为ES-SCLC[2]。近40年来，化疗对ES-SCLC患者的生存改善甚微，2019年美国SEER数据库公布了1973—2010年肺癌5年生存率，结果显示，4种不同病理类型的肺癌的5年总生存（overall survival，OS）率均呈升高的趋势，但ES-SCLC仅提高2.8%～7.2%[3]。 LS-SCLC的初始治疗方法与分期有关，手术在极早期SCLC患者具有重要价值，LS-SCLC的同步放化疗（concurrent chemoradiotherapy，同步放化疗）是基石治疗，但由于易复发和耐药性问题，超50%的患者在2年内疾病复发，5年生存率仅约25%，因此，临床亟需探寻更有效的治疗手段。ES-SCLC对化疗敏感但极易复发，多项针对生长因子和细胞凋亡靶点的药物探索以及抗血管生成治疗研究相继失败，ES-SCLC靶向治疗探索受阻。在进入免疫治疗时代前，ES-SCLC药物治疗无突破，中位总生存（median overall survival，mOS）时间＜1年，5年OS率＜2%。免疫治疗打破了化疗时代的生存瓶颈，让ES-SCLC治疗焕发生机。免疫治疗探索是从后线开始的，但对后线和一线维持治疗无生存获益，一线起始加入免疫药物可带来生存获益。2018—2024年，以IMpower133、CASPIAN、ASTRUM-005、CAPSTONE-1研究为代表的免疫治疗联合化疗模式实现了历史性突破，为ES-SCLC患者带来长生存希望。与此同时，如何使SCLC患者获得最大化的免疫治疗获益是一个新的难题。2024年众多研究对SCLC开展多种治疗形式组合，其中不乏亮点，本文旨在归纳2024年度SCLC的治疗研究进展。 ✦✦ 1 局限期小细胞肺癌一线治疗既往针对LS-SCLC的标准系统性治疗方案一直是同步放化疗或序贯放化疗，随着程序性死亡受体配体1（programmed death-ligand 1，PD-L1）抑制剂在ES-SCLC治疗领域取得突破，其能否突破LS-SCLC的治疗瓶颈也备受关注。 ✦✦ 1.1 ADRIATIC模式成为LS-SCLC治疗新标准 ADRIATIC研究是一项探索LS-SCLC同步放化疗后度伐利尤单抗联合/不联合Tremelimumab巩固治疗的安全性及有效性的Ⅲ期研究。2024年公布了该研究度伐利尤单抗组初步疗效及安全性数据。结果显示，对比安慰剂，度伐利尤单抗免疫巩固在同步放化疗后未出现进展的LS-SCLC患者中显著延长了mOS时间（55.9个月∶33.4个月，P=0.010 4）与中位无进展生存（median progression-free survival，mPFS）时间（16.6个月∶9.2个月，P=0.016 1），且耐受性良好，3级以上不良事件发生率（24.3%∶24.2%）、不良事件导致治疗停止发生率（16.3%∶10.6%）及死亡发生率（2.7%∶1.9%）均无明显差异，未增加安全风险[4]。进一步的分析显示，度伐利尤单抗免疫巩固2年PFS率为46.2%。亚组分析结果显示，同步放化疗后最佳疗效为疾病稳定的患者从巩固免疫治疗中获益的程度较达到部分疾病缓解或完全缓解的患者更为显著，提示目前尚无法准确判断接受免疫巩固治疗的精准获益人群，同步放化疗后未达客观缓解的患者可能是免疫巩固治疗的主要获益人群。此外，无论放射治疗（以下简称放疗）频次、同步化疗方案以及预防性脑放疗治疗如何，度伐利尤单抗巩固治疗均较安慰剂显著改善了患者的OS时间和PFS时间[5]。从广泛期到局限期，免疫治疗不断突破SCLC患者获益的边界，ADRIATIC研究成功探索了免疫治疗作为LS-SCLC同步放化疗后维持治疗方案的有效性及安全性。ADRIATIC研究是全球首个双重终点均取得阳性结果的LS-SCLC患者同步放化疗后免疫巩固治疗Ⅲ期临床试验，改变了LS-SCLC以根治性放化疗为基础的治疗模式，建立了LS-SCLC治疗新标准。 ✦✦ 1.2 联合免疫治疗 LS-SCLC的免疫治疗目前主要有同步放化疗后序贯免疫治疗和免疫同步放化疗后免疫巩固治疗2种模式。 1.2.1 同步放化疗后序贯免疫治疗 STIMULI研究是评估纳武利尤单抗联合伊匹木单抗巩固治疗（双免联合组）LS-SCLC疗效的Ⅱ期临床研究。结果显示，双免联合组与观察组（单独使用标准放化疗）mPFS时间（10.7个月∶14.5个月，HR＝1.02，95%CI为0.66～1.58，P＝0.93）、1年PFS率（48.1%∶52.8%）、2年PFS率（43.2%∶40.3%）比较差异均无统计学意义。双免联合组中55.1%的患者因治疗相关不良反应终止治疗[6]。STIMULI研究中双免联合组未取得生存获益，可能是治疗相关毒性和过高的治疗终止比例影响了研究结果。而Ⅲ期的ADRIATIC研究度伐利尤单抗巩固治疗显著提高生存，可能与其安全性良好，因不良反应终止治疗率低有关。 1.2.2 免疫同步放化疗后免疫巩固治疗 AdvanTIG-204研究是一项评估ociperlimab（T细胞免疫球蛋白单克隆抗体）＋替雷利珠单抗＋同步放化疗一线治疗LS-SCLC的初步疗效和安全性的随机、多中心、Ⅱ期临床研究。结果表明，与同步放化疗相比，替雷利珠单抗联合同步放化疗仅有改善初治ES-SCLC患者PFS时间和客观缓解率（objective response rate，ORR）的趋势，但均无统计学差异[7]。NRG-LU005是一项国际多中心Ⅲ期随机对照临床研究，旨在探究同步放化疗联合免疫治疗的疗效及安全性。2024年报告了第2次中期分析结果，与同步放化疗相比，同步放化疗联合阿替利珠单抗未能显著延长LS-SCLC患者的mOS时间（33.1个月∶39.5个月，HR＝1.11，95%CI为0.85～1.45）和mPFS时间（12.0个月∶11.5个月，HR＝1.00，95%CI为0.80～1.25）[8]。NCT04691063是一项评估阿得贝利单抗联合同步放化疗治疗LS-SCLC的2阶段Ⅲ期临床研究，2024年首次披露了该研究安全性导入期的结果。在安全导入期，阿得贝利单抗联合同步放化疗在LS-SCLC中表现出可耐受的安全性，≥3级治疗相关不良事件发生率较高为96.4%，但发生率≥10%的事件均为血液学毒性，治疗相关肺炎发生率为14.3%，仅1例患者因输液相关反应导致停止治疗，无因治疗相关不良事件导致死亡的病例。此外阿得贝利单抗联合同步放化疗初步治疗效果良好[ORR为92.9%，疾病控制率（disease control rate，DCR）为100%，中位缓解持续（median duration of response，mDOR）时间为20.1个月，mPFS时间为17.9个月，mOS时间未达到]。该试验的随机、双盲、安慰剂对照阶段正在进行，以进一步评估该治疗方案[9]。 ✦✦ 2 广泛期小细胞肺癌一线治疗 ES-SCLC因其恶性程度高，具有治疗后快速进展的疾病特征，一线化疗联合免疫治疗mPFS时间提升有限，6个月后免疫药物才逐渐出现PFS获益，表现出拖尾效应，因此，需要进一步强化治疗方案延缓进展。 ✦✦ 2.1 联合抗血管生成药物 ETER701研究显示，贝莫苏拜单抗（PD-L1抑制剂）＋安罗替尼＋依托泊苷＋卡铂四药联合模式在ES-SCLC一线治疗中有突出疗效，可显著改善患者生存期，mOS时间达17.8个月，较对照组（安慰剂＋依托泊苷＋卡铂）延长了5.6个月，mPFS时间达6.9个月，较对照组延长了2.7个月，为ES-SCLC一线治疗提供PFS时间和OS时间更优的新高效方案[10]。2024年公布了安罗替尼联合化疗的三药治疗组的疗效，与单独化疗组相比，显著延长了mPFS（5.6个月∶4.2个月，P＜0.000 1），但mOS时间无显著获益（13.3个月∶11.9个月，P=0.173 2）[10]，提示免疫联合安罗替尼和化疗可以带来更好的协同作用。由于ETER701研究未设置化疗联合免疫的一线标准方案作为对照，且三药及四药方案潜在增加安全性风险。尽管免疫联合安罗替尼及化疗是否可成为ES-SCLC一线治疗新标准有待商榷，但为临床提供了一个高效的方案。BEAT-SC研究是全球首个以免疫联合化疗作为标准对照，探索贝伐珠单抗联合免疫及化疗一线治疗ES-SCLC疗效及安全性的随机、对照、国际多中心Ⅲ期研究。2024年公布了BEAT-SC研究PFS时间初步分析和OS时间中期分析结果，与安慰剂组相比，贝伐珠单抗联合组可显著延长mPFS时间（5.7个月∶4.4个月，HR＝0.70，95%CI为0.54～0.90，P=0.006 0），但mOS时间未显著获益（13.0个月∶16.6个月，HR＝1.22；95%CI为0.89～1.67，P=0.221 2）[11]。综合分析目前公布的研究数据，不同四药联合治疗方案的疗效数据存在差异，因此，治疗方案的选择不仅要遵循高级别循证医学证据，还需综合考量疗效与安全性，为ES-SCLC患者选择个体化治疗方案。 DURABLE研究是一项随机对照、多中心的Ⅱ期临床试验，旨在评估度伐利尤单抗联合安罗替尼与度伐利尤单抗单药作为ES-SCLC患者维持治疗的疗效和安全性[12]。与度伐利尤单抗单药维持治疗相比，度伐利尤单抗联合安罗替尼维持治疗将mPFS时间从1.9个月延长至5.4个月，mOS时间从12.4个月延长至17.4个月，整体mOS时间也明显延长（20.4个月∶15.4个月）[12]。结果提示，度伐利尤单抗联合安罗替尼在安全性方面具有一定优势，同时疗效也并不逊色于四药联合治疗方案。另一项多中心、前瞻性、单臂、开放标签的真实世界研究评估阿替利珠单抗联合安罗替尼作为维持治疗方案在ES-SCLC一线治疗的临床获益，共纳入53例ES-SCLC患者，ORR为79.2%，DCR为94.3%，mPFS时间达9个月[13]。以上研究表明，维持治疗阶段引入抗肿瘤血管生成药物，从而在疗效与安全性之间实现更好的平衡，为未来的治疗策略提供了新的思路。 ✦✦ 2.2 联合胸部放疗约90%的ES-SCLC患者一线化疗后1年内可能出现胸部病灶进展。CREST研究结果显示，与未联合胸部放疗相比，ES-SCLC患者化疗诱导治疗缓解后联合胸部放疗，2年OS率显著提升（13%∶3%，P＝0.004），胸部病灶复发率显著降低（43.7%∶79.8%，P<0.000 1）[14]。表明，胸部放疗在免疫时代仍有应用价值，二者联合使用在临床前研究和临床研究中有协同作用。 2023年公布了单臂、Ⅱ期的MATCH研究探索IMpower133模式联合同步低剂量胸部放疗（low dose radiotherapy，LDRT）（15 Gy/5f）一线治疗ES-SCLC的疗效和安全性数据，ORR为87.5%，mPFS时间为6.9个月，较IMpower133模式mPFS时间提升1个月[15]。LEAD是一项单臂、多中心、Ⅱ期研究，旨在评估CASPIAN模式联合LDRT的获益情况，2024年公布其初步疗效数据，度伐利尤单抗联合化疗和LDRT一线治疗ES-SCLC患者mPFS时间为8.3个月，较CASPIAN研究中的mPFS时间（5.1个月）明显延长，mOS时间尚未达到[16]。 2024年报告了一项阿得贝利单抗联合化疗序贯胸部放疗一线治疗ES-SCLC的Ⅱ期探索性研究，该研究共纳入67例ES-SCLC患者，研究结果显示，ES-SCLC免疫治疗联合胸部放疗可使患者短期获益和长期获益均有显著改善，mPFS时间为10.1个月，mOS时间为21.4个月。同时具有良好的安全性，≥3级治疗相关不良事件发生率为58.2%，其中≥3级肺炎仅6%[17]。NRG-LU007/RAPTOR研究旨在验证阿替利珠单抗联合胸腔放疗＋转移灶放疗在一线化疗联合免疫治疗后稳定及以上ES-SCLC的获益，期待研究结果。多项Ⅱ期临床研究已证实免疫联合化疗基础上再联合放疗有望提高SCLC患者的生存获益，多项Ⅲ期临床研究正在进行，仍需进一步探索胸部放疗的获益人群筛选、最佳放疗剂量及分割模式、放疗加入时机等问题。 ✦✦ 3 小细胞肺癌二线及后线治疗新进展 ✦✦ 3.1 DLL3/CD3双特异性抗体 Delta样配体3（Delta-like ligand 3，DLL3）是一种抑制Notch信号的蛋白，在85%的SCLC细胞表面异常表达，是SCLC的潜在治疗靶点。tarlatamab是一种靶向DLL3和CD3的双特异性T淋巴细胞衔接器，通过同时与肿瘤细胞上的DLL3和T淋巴细胞上的CD3相结合，导致T淋巴细胞介导的肿瘤细胞裂解，从而起到肿瘤杀伤的作用。在Ⅰ期剂量探索试验DeLLphi-300研究（NCT03319940）中tarlatamab用于SCLC后线治疗的ORR达23%，mOS时间为13.2个月，mPFS时间为3.7个月，值得注意的是，mDOR时间长达13个月，是具有里程碑意义的重大突破[18]。Ⅱ期DeLLphi-301研究进一步探索了不同剂量tarlatamab（10 mg/100 mg）用于SCLC二线以上治疗的疗效，tarlatamab在经治SCLC患者中显示出持久的反应和良好的安全性[19]。2024年公布了DeLLphi-301研究扩展随访的疗效和安全性结果，10 mg剂量组的ORR达40%，mPFS时间为4.3个月，mOS时间为15.2个月，长期耐受性良好，且无新的安全信号[20]。DeLLphi-303研究是采用tarlatamab联合PD-L1抑制剂作为ES-SCLC一线化疗联合免疫治疗后的维持治疗的Ⅰb期临床研究，2024年报道了其初步研究结果，tarlatamab＋PD-L1抑制剂的DCR为62.5%，中位疾病控制的持续时间为9.3个月。Tarlatamab分别联合度伐利尤单抗和阿替利珠单抗维持治疗9个月的OS率为91.8%和86.7%，mPFS时间分别为5.3个月和5.6个月，均高于PD-L1抑制剂单药，PFS时间和OS时间获益明显[21]。基于上述结果，tarlatamab已经成为ES-SCLC治疗重要药物，未来如何与其他治疗配合且能否进一步提高疗效值得积极探索。 MK-6070是靶向DLL3/CD3/Ablumin的三抗。MK-6070-001/HPN328-4001研究是一项评估MK-6070单药以及联合阿替利珠单抗治疗晚期DLL3阳性实体瘤疗效和安全性的临床Ⅰ/Ⅱ期试验（NCT04471727）。截至2024年2月9日，共纳入49例SCLC患者接受了≥1.215 mg MK-6070的治疗。结果显示，无论是否基线存在脑转移，MK-6070对经治SCLC患者显示具有良好的抗肿瘤潜力[22]。 ✦✦ 3.2 抗体药物偶联物（antibody-drug conjugate，ADC）新靶点 3.2.1 共刺激分子B7H3（costimulatory molecule B7H3，B7H3） B7H3作为一种免疫检查点蛋白，在约65%的SCLC具有中高表达，与疾病的侵袭性和不良预后密切相关，因此B7H3是治疗的理想靶点[23-25]。 DXd是一种靶向B7H3的ADC。Ⅰ/Ⅱ期DS7300-A-J101研究旨在评估I-DXd治疗晚期实体瘤的疗效与安全性，共纳入22例经治的ES-SCLC患者，ORR达52.4%，mPFS时间为5.6个月，mOS时间为12.2个月，mDOR时间为5.9个月，提示I-DXd用于治疗SCLC具有巨大临床潜力[26]。2024年公布了关键Ⅱ期IDeate-Lung01临床研究剂量优化部分的期中分析结果，I-DXd在最佳的剂量12 mg/kg组中，ORR达54.8%，mPFS时间和mOS时间分别为5.5个月和11.8个月[26]，进一步验证了I-DXd在ES-SCLC中的疗效，其中脑转移亚组数据显示，I-DXd在ES-SCLC颅内反应率为50.0%，具有优异的颅内疗效的潜力。基于Ⅱ期研究的积极结果，Ⅲ期IDeate-Lung02研究已经启动，旨在评估I-DXd对比化疗在仅接受过一线治疗复发性SCLC患者中的疗效及安全性。此外，I-DXd联合治疗的模式正在探索。 3.2.2 滋养层细胞表面抗原2（trophoblast cell surface antigen 2，TROP2） TROP2是一种表达于上皮细胞表面的跨膜糖蛋白，在多种实体瘤中呈过表达，并参与了肿瘤的发生、侵袭和转移过程，是一个潜在的肿瘤治疗靶点。TROP2是一类内化的细胞膜受体，能使以其为靶点的ADC进入细胞内溶酶体并释放更具细胞渗透性的细胞毒性有效负载，产生更强的旁观者效应。戈沙妥珠单抗（sacituzumab govitecan，SG）是一种靶向TROP2的ADC。TROPiCS-03（NCT03964727）研究是一项开放标签、篮式设计的多队列、Ⅱ期临床试验，旨在评估戈沙妥珠单抗用于NSCLC、ES-SCLC、子宫内膜癌等多种实体瘤的疗效与安全性[27]。其中纳入了43例不超过一线含铂化疗和免疫治疗后疾病进展的ES-SCLC患者，有20例（46.5%）属于铂类药物耐药（化疗无疾病间隔＜90 d）。2024年公布的疗效分析数据显示，ORR为41.9%，临床获益率（clinical benefit rate，CBR）为48.8%，mDOR时间为4.73个月，mPFS时间为4.40个月，mOS时间为13.60个月；对铂类药物耐药和对铂类药物敏感的患者中均显示出抗肿瘤活性（ORR分别为35.0%和47.8%）[27]。研究结果提示，戈沙妥珠单抗作为ES-SCLC的二线治疗具有良好的抗肿瘤活性和可控的安全性。 ✦✦ 4 总结与展望 SCLC侵袭性强、预后极差，40余年来研究进展缓慢，近年来，免疫疗法和其他新型药物的研究进展为SCLC治疗带来了突破。回顾2024年，SCLC的治疗稳步向前，ADRIATIC研究成功探索了免疫治疗作为LS-SCLC同步放化疗后维持治疗方案的有效性及安全性，改变LS-SCLC治疗格局；ES-SCLC现有后线治疗方案效果有限，患者生存获益主要来源于一线治疗，对于延缓一线治疗进展、提高免疫治疗的获益人群，联合治疗方案包括抗血管生成治疗和胸部放疗初见成效；DLL3作为SCLC治疗新靶点，后线治疗取得突破，联合治疗方案逐渐前移；ADC中B7H3和TROP2作为新靶点备受瞩目，但仍需大样本数据和Ⅲ期临床研究。整体而言，联合治疗仍是SCLC未来探索的热点，新机制、新靶点的药物研究也将为SCLC的治疗带来新的希望。参考文献向上滑动查看 [1] SUNG H, FERLAY J, SIEGAL R L, et al. 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J Thorac Oncol, 2024, 19(10):S31-S32. [22] CHOUDHURY N J, BELTRAN H, JOHNSON M L, et al. OA10.06 impact of brain metastases on safety and efficacy of MK-6070, a DLL3-Targeting T cell engager, in small cell lung cancer[J]. J Thorac Oncol, 2024, 19(10):S32-S33. [23] DONG P, XIONG Y, YUE J, et al. B7H3 as a promoter of metastasis and promising therapeutic target[J]. Front Oncol, 2018, 8:264. [24] Qiu M J, Xia Q, Chen Y B, et al. The expression of three negative co-stimulatory b7 family molecules in small cell lung cancer and their effect on prognosis[J]. Front Oncol, 2021, 11:600238. [25] CARVAJAL-HAUSDORF D, ALTAN M, VELCHETI V, et al. Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung cancer (SCLC)[J]. J Immunother Cancer, 2019, 8, 7(1):65. [26] RUDIN C, JOHNSON M, GIRARD N, et al. P2.16-06 a phase 2 study of ifinatamab deruxtecan (I-DXd; DS-7300) in patients with previously treated ES-SCLC[J]. J Thorac Oncol, 2023, 18(11):S377. [27] DOWLATI A, CHIANG A C, CERVANTES A, et al. OA04.04 sacituzumab govitecan as second-line treatment in patients with extensive stage small cell lung cancer[J]. J Thorac Oncol, 2024, 19(10):S16. 推荐阅读 ● 盘点2023 | 黄鼎智教授：2023年度小细胞肺癌治疗研究进展 ● 盘点2022丨黄鼎智教授：2022年度小细胞肺癌治疗进展 ● 2023年度肿瘤学科盘点集锦(共17个) 声明：本文由“肿瘤界”整理与汇编，欢迎分享转载，如需使用本文内容，请务必注明出处。排版：lagertha 校对：松月

CSCO会议临床3期免疫疗法

2024-12-17

·UmabsDB

科伦启动B7H3 ADC临床试验

Umabs DB作为目前全球最全面的抗体药物专业数据库，收录全球近10000个从临床前到商业化阶段抗体药物，涉及靶点1600+，涉及疾病种类2400+，研发机构2900+，覆盖药物蛋白序列、专利和临床等多种专业信息。Umabs DB药物数据库已正式开放上线，可访问www.umabs.com注册享受7天免费试用。近期，根据UmabsDB数据库的记录，科伦博泰在clinical trials网站上，登记了一项ADC药物SKB500 ，在多种晚期实体瘤患者中启动一项1期临床试验NCT06736327，该临床将于2024年12月启动，计划入组人数为180例。在其临床登记信息中，显示了将探索B7-H3的表达和抗肿瘤活性之间的关系，推测SKB500为一款B7-H3 ADC药物的专利。国内的临床信息登记平台方面，显示该临床的主要研究者为吉林省肿瘤医药的程颖教授，其近年来成为国内首屈一指的小细胞肺癌药物临床专家，翰森和第一三共作为全球最快的两款B7-H3 ADC，均在程颖教授的中心开展三期临床试验（翰森和第一三共先后启动B7H3 ADC国内三期临床试验）。 SKB500是利用OptiDCTM平台技术研发的具有自主知识产权的新型ADC药物，在临床前研究中显示出良好的疗效和安全窗，拟用于治疗晚期实体瘤。根据科伦披露的专利，SKB500抗体部分采用杂交瘤技术进行筛选得到人源化后的抗体2#8900，亲和力方面优于第一三共的抗体DS7300。同时值得注意的是，与DS7300保留ADCC功能的不同是，科伦抗体并没有保留ADCC功能，这也是其差异化的功能之一，未来值得关注（ADCC效应对于双抗或ADC的必要性）。 ADC的构造方面，科伦设置了多种候选变体，但是后期主要测试了两款ADC，ADC5和ADC9，毒素分别来自于以下的A-05和A-14，DAR值均为8。体外活性及内吞活性方面，SKB500均优于第一三共DS7300。体内的肿瘤抑制效果方面，同样是ADC5和ADC9最优，SKB500应优选为其中之一。科伦作为国内第一波开发的第一代ADC药物的公司，目前TROP2 ADC已经批准上市（科伦博泰：本土首款Trop2 ADC获批上市），HER2 ADC还处于上市评审阶段，但是成熟靶点或半成熟靶点的follow/迭代药物总是热门标的，优秀靶点仍然稀缺（身处靶点稀缺的伟大时代），后期如SKB500等项目仍然表现同质化，甚至在开发进度毫无优势，这也是目前创新药群雄涿鹿的年代，谁也不可能通吃整个领域，合作共赢才能将优势最大化。期待SKB500该临床早日传来临床捷报，更多有关抗体的研发格局、具体信息、专利及临床等动态进展，敬请访问Umabs DB全球数据库（www.umabs.com）查阅。拓展阅读：国内首款：诗健启动TROP2 ADC三阴乳腺癌一线三期临床一线胃癌头对头：第一三共启动HER2 ADC+PD-1三期临床康方即将启动HER3 ADC临床试验 PD-1+TIGIT：吉利德启动一线头颈鳞癌联合疗法临床 Celldex启动KIT抗体特应性皮炎2期临床中位OS提高10.9个月：Immutep启动LAG-3+PD-1一线非小细胞肺癌头对头三期临床试验 Macrogenics启动下一代ADAM9 ADC临床 100% CR：默沙东更新ROR1 ADC二期淋巴瘤临床数据，即将启动三期临床 MSD：收购PD-1/VEGF双抗后的回应 HIV：中裕新药将ADC拓展至抗病毒领域全球首个：默沙东ROR1 ADC启动三期临床试验 HER3终成药：HER2/HER3双抗Zenocutuzumab获FDA批准上市百利天恒两款ADC在美启动临床 3000万美元首付：GSK引进映恩一款临床前ADC药物 “四字编码”时代下的信达全梳理 BioNtech启动PD-L1/VEGF双抗肺癌两项头对头三期临床大涨68%：Janux的PSMA/CD3双抗再次取得突破疗效 316例：诺华启动BAFF-R抗体在狼疮性肾炎的三期临床 250例：默克CEACAM5 ADC开展泛癌种临床试验 AK112 vs PM8002：PD-1/VEGF第三次交锋康方生物两款PD-1双抗均进入2024年医保目录 234例：安领科启动EGFR/c-Met双抗ADC临床科伦博泰：本土首款Trop2 ADC获批上市罗氏TIGIT抗体一线肺癌再次失败 876例：恒瑞启动c-met ADC单药及多种药物联用临床科伦博泰首个双抗ADC启动临床阿斯利康：ADC药物的临床剂量转化策略最惨18A：北海康成市值仅为7520万港元，累计跌幅达到98.55% 2~3分钟完成给药：K药皮下制剂三期临床取得成功 ORR仅为5%：Immatics公布PRAME/CD3 TCR双抗临床数据石药启动EGFR ADC+ATM抑制剂联合治疗临床康方启动CD73/LAG3双抗临床试验宫颈癌：迈威Nectin-4 ADC启动第3项三期临床大涨53%：中国资产再次拯救美股biotech 翰森HS-20124为ROR-1 ADC药物？翰森公开SEZ6 ADC专利翰森公开CDH17 ADC专利复宏汉霖公布两款ADC药物专利 BioNtech: 2024研发日默沙东终于信了：5.88亿美元首付款引进礼新PD-1/VEGF双抗映恩公开PD-L1/B7H3双抗ADC临床前数据 Hexagon：新型ADC毒素提高渗透性：antikor开发高DAR值片段抗体ADC Genmab终止两款CD3双抗开发，重聚焦后期管线第一三共开发皮下HER2 ADC 三抗来袭：Aditum Bio以3500万美元首付款引进维立志博CD3/CD19/BCMA 强生公布膜依赖性MSLN/CD3双抗金赛公开自主开发TOPOi ADC平台礼来公布PTK7 ADC药物临床前数据双payload ADC逐步工业化，多款药物即将进入临床恒瑞SHR-A2009：国内首个HER3 ADC进入三期 ADC：抗原高表达的必要性？关于Umabs DB Umabs DB是目前全球最全面的抗体药物专业数据库，收录全球近10000个从临床前到商业化阶段抗体药物，涉及靶点1600+，涉及疾病种类2400+，研发机构2900+，覆盖药物蛋白序列、专利和临床等多种专业信息。Umabs DB药物数据库已正式开放上线，可访问www.umabs.com注册享受7天免费试用，更多信息可联系info@umabs.com

抗体药物偶联物临床3期临床1期引进/卖出临床2期

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
复发性小细胞肺癌	临床3期	美国	Daiichi Sankyo Co., Ltd.	2024-05-21
复发性小细胞肺癌	临床3期	美国	Merck Sharp & Dohme LLC	2024-05-21
复发性小细胞肺癌	临床3期	中国	Daiichi Sankyo Co., Ltd.	2024-05-21
复发性小细胞肺癌	临床3期	中国	Merck Sharp & Dohme LLC	2024-05-21
复发性小细胞肺癌	临床3期	日本	Merck Sharp & Dohme LLC	2024-05-21
复发性小细胞肺癌	临床3期	日本	Daiichi Sankyo Co., Ltd.	2024-05-21
复发性小细胞肺癌	临床3期	澳大利亚	Merck Sharp & Dohme LLC	2024-05-21
复发性小细胞肺癌	临床3期	澳大利亚	Daiichi Sankyo Co., Ltd.	2024-05-21
复发性小细胞肺癌	临床3期	奥地利	Merck Sharp & Dohme LLC	2024-05-21

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临床结果

适应症

分期

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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 \| 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	齋製選願鹹鹽醖鏇獵艱(糧鏇網簾餘製壓鹹顧製) = 窪簾膚壓鬱願蓋壓願淵積鑰鏇獵憲鏇鏇襯遞齋 (築製鹽鑰壓顧選糧獵膚 ) 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	齋範築窪壓壓繭糧襯顧(積艱餘鬱選範廠鹽糧衊) = 憲範憲鏇網鹹製鬱積製遞餘簾廠鬱襯繭願願窪 (夢衊淵壓膚膚壓餘餘衊, 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	齋範築窪壓壓繭糧襯顧(積艱餘鬱選範廠鹽糧衊) = 觸構製願鬱窪餘積艱遞遞餘簾廠鬱襯繭願願窪 (夢衊淵壓膚膚壓餘餘衊, 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)	鏇範繭觸鏇夢繭繭衊淵(窪膚鹽窪築築鑰膚簾願) = 鹹範餘製範積構製範淵鹹鑰壓膚鑰鬱構餘構壓 (願網願簾製壓遞齋積糧 ) 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)	鏇範繭觸鏇夢繭繭衊淵(窪膚鹽窪築築鑰膚簾願) = 艱夢鑰艱築艱鹽遞夢憲鹹鑰壓膚鑰鬱構餘構壓 (願網願簾製壓遞齋積糧 ) 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	築網獵獵膚淵構網艱繭(艱範醖鏇壓繭願糧積窪) = 範願夢窪鏇衊鑰糧蓋衊襯遞鏇廠積積艱觸膚廠 (遞選鬱鏇衊願鬱膚衊艱 ) 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)	襯網鏇網鏇艱艱鏇淵製(範醖衊構範憲網憲範艱) = 廠願衊顧鏇膚遞網醖鬱憲糧鹽鬱齋獵顧網鹽鑰 (餘鏇蓋網廠網蓋繭顧膚 ) 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)	襯網鏇網鏇艱艱鏇淵製(範醖衊構範憲網憲範艱) = 夢醖醖願壓遞積製襯艱憲糧鹽鬱齋獵顧網鹽鑰 (餘鏇蓋網廠網蓋繭顧膚 ) 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	鹹鹹艱獵齋糧遞壓構夢(製顧壓獵獵鏇鬱襯淵艱) = 製積繭選製鏇選衊顧繭遞廠願鬱觸鏇製艱鬱簾 (衊製獵窪憲艱遞鹹網鑰 ) 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	醖糧觸遞鏇艱憲網獵選(夢憲憲鏇襯齋蓋繭觸衊) = 繭憲艱顧艱窪鹽糧蓋襯壓淵網獵壓遞糧積醖鹽 (餘選製構範鹽糧醖壓餘 ) 更多	积极	2021-09-17