LIGHTBEAM-U01 Substudy 01A: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors

Substudy 01A is part of a platform study. The purpose of this study is to assess the efficacy and safety of zilovertamab vedotin in pediatric participants with elapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL)/Burkitt lymphoma, or neuroblastoma and in pediatric and young adult participants with Ewing sarcoma.

开始日期2024-06-27

申办/合作机构

Merck Sharp & Dohme LLC

CTR20232196 / Recruiting临床2/3期

一项在复发性或难治性弥漫性大B细胞淋巴瘤受试者中评价MK-2140联合标准治疗的2/3期多中心、开放性、随机、阳性对照研究

主要目的：评价MK-2140与R-GemOx和BR联合使用时的安全性和耐受性，并确定RP2D；由BICR（盲态独立中心审查）根据Lugano疗效评价标准比较MK-2140联合R-GemOx与R-GemOx的PFS；由BICR根据Lugano疗效评价标准比较MK-2140联合BR与BR的PFS 次要目的：比较MK-2140联合R-GemOx与R-GemOx的OS，ORR（BICR）和DOR（BICR）；比较MK-2140联合BR与BR的OS，ORR（BICR）和DOR（BICR）。

开始日期2024-01-08

申办/合作机构

默沙东研发（中国）有限公司

CTR20222465 / Recruiting临床2期

一项在侵袭性和惰性B细胞恶性肿瘤受试者中评价MK-2140单药治疗和联合治疗的安全性和有效性的多中心、开放性、II期篮式研究（waveLINE-006）

主要目的：队列D：评价MK-2140的安全性和耐受性；所有队列：评价MK-2140的客观缓解率；次要目的：所有队列：评价MK-2140的缓解持续时间；队列A、B和E：评价MK-2140的安全性和耐受性。

开始日期2022-11-24

申办/合作机构

默沙东研发（中国）有限公司

100 项与 Zilovertamab vedotin 相关的临床结果

登录后查看更多信息

100 项与 Zilovertamab vedotin 相关的转化医学

登录后查看更多信息

100 项与 Zilovertamab vedotin 相关的专利（医药）

登录后查看更多信息

项与 Zilovertamab vedotin 相关的文献（医药）

2023-11-01·Leukemia research

The shifting therapeutic paradigm for relapsed/refractory mantle cell lymphoma

Review

作者: Patel, Shyam A ; Arun Kumar, Sumukh ; Gao, Jenny

Mantle cell lymphoma (MCL) is a heterogeneous subtype of non-Hodgkin lymphoma that has been historically associated with poor 5-year overall survival rates, especially for aggressive variants. Traditional cytotoxic chemotherapy had been a mainstay of therapy for relapsed/refractory (R/R) MCL for many years until the advent of molecularly targeted therapies and cell-based approaches. However, a significant concern is the lack of definitive consensus guidelines for management of R/R MCL. The managerial conundrum partly stems from the absence of head-to-head comparisons of novel therapies, with conclusions drawn from cross-trial comparisons. In this evidence-based review, we discuss the current therapeutic options for R/R MCL, including the most recent data from the BRUIN study that led to the approval of the first-in-class non-covalent reversible Bruton's tyrosine kinase (BTK) inhibitor pirtobrutinib in 2023, as well as the recent removal of ibrutinib from the market. We discuss outlooks for targeted therapy and tolerability considerations for novel agents, including unique considerations for the elderly population. We highlight emerging data that support the curative potential of chimeric antigen receptor-T (CAR-T) therapy from ZUMA-2, relative to other promising investigational agents in the pipeline, including glofitamab, epcoritamab, and zilovertamab vedotin. We summarize management recommendations based upon the most rigorous clinical evidence to date.

2021-12-01·Journal of hematology & oncology

The antibody drug conjugate VLS-101 targeting ROR1 is effective in CAR T-resistant mantle cell lymphoma

Letter

作者: Che, Yuxuan ; Jessen, Katti A ; Wang, Michael ; Lannutti, Brian J ; Jiang, Vivian Changying ; Li, Yijing ; Jordan, Alexa ; Liu, Yang ; McIntosh, Joseph

Abstract:

Mantle cell lymphoma (MCL) is a rare, aggressive and incurable subtype of non-Hodgkin’s B-cell lymphoma. The principal barrier is frequent clinical relapse to multiple lines of therapies, including new FDA-approved biologics and cell therapy. Brexucabtagene autoleucel, the first and only FDA approved chimeric antigen receptor (CAR) T product in MCL, demonstrated unprecedented efficacy in overcoming resistance to Bruton’s tyrosine kinase inhibitors. However, relapses have inevitably occurred and once relapsed these patients display a very poor clinical outcome. Currently, there is no optional therapy specifically designed for these patients. The development of tailored and more efficacious therapies is therefore critical and represents a new medical need. We found that while the receptor tyrosine kinase-like orphan receptor 1 (ROR1) is expressed across most of the MCL cells, it is significantly elevated in CAR T-relapsed MCL tumors. To see whether this aberrant ROR1 expression contributed to CAR T resistance, we targeted ROR1 using VLS-101, a monomethyl auristatin E conjugated anti-ROR1 antibody. VLS-101 showed potent anti-MCL activity in vitro in ROR1-expressing MCL cell lines and ex vivo in primary patient samples. Importantly, VLS-101 safely induced tumor regression in PDX models resistant to CAR T-cell therapy, ibrutinib and/or venetoclax. These data advocate for targeting ROR1 as a viable approach in the treatment of ROR1-positive MCL tumors, especially those with failure to prior therapies. These data also provide strong evidence for future enrollment of post-CD19 CAR T-cell relapsed MCL patients in a first in-human phase 1b VLS-101 trial. The upcoming testing in a clinical setting will provide important insights on this new therapeutic development aiming to overcome the CAR T resistance via targeting ROR1, which is a rising unmet clinical need in MCL.

2021-06-17·Blood1区 · 医学

ROR1 targeting with the antibody-drug conjugate VLS-101 is effective in Richter syndrome patient–derived xenograft mouse models

1区 · 医学

Article

作者: Vaisitti, Tiziana ; Allan, John N. ; Braggio, Esteban ; Iannello, Andrea ; Lannutti, Brian J. ; Di Napoli, Arianna ; Lee, Thanh-Trang ; Vitale, Nicoletta ; Deaglio, Silvia ; Miller, Langdon L. ; Chadburn, Amy ; Arruga, Francesca ; Furman, Richard R. ; Ko, Mira ; Jessen, Katti A.

Abstract:

Richter syndrome (RS) represents the transformation of chronic lymphocytic leukemia (CLL), typically to an aggressive lymphoma. Treatment options for RS are limited and the disease is often fatal. Receptor tyrosine kinase–like orphan receptor 1 (ROR1) is expressed on CLL cells and other cancers but not on healthy adult tissues, making it an attractive, tumor-specific therapeutic target. VLS-101 is being developed as an antibody-drug conjugate (ADC) for therapy of ROR1-expressing (ROR1+) cancers. VLS-101 comprises UC-961 (a humanized immunoglobulin G1 monoclonal antibody that binds an extracellular epitope of human ROR1), a maleimidocaproyl-valine-citrulline-para-aminobenzoate linker, and the antimicrotubule cytotoxin monomethyl auristatin E (MMAE). VLS-101 binding to ROR1 results in rapid cellular internalization and delivery of MMAE to induce tumor cell death. We studied 4 RS patient-derived xenografts (RS-PDXs) with varying levels of ROR1 expression (11%, 32%, 85%, and 99% of cells). VLS-101 showed no efficacy in the lowest-expressing RS-PDX but induced complete remissions in those with higher levels of ROR1 expression. Responses were maintained during the posttherapy period, particularly after higher VLS-101 doses. In systemic ROR1+ RS-PDXs, VLS-101 dramatically decreased tumor burden in all RS-colonized tissues and significantly prolonged survival. Animals showed no adverse effects or weight loss. Our results confirm ROR1 as a target in RS and demonstrate the therapeutic potential of using an ADC directed toward ROR1 for the treatment of hematological cancers. A phase 1 clinical trial of VLS-101 (NCT03833180) is ongoing in patients with RS and other hematological malignancies.

项与 Zilovertamab vedotin 相关的新闻（医药）

2024-06-13

·echemi

Sutro Biopharma and Ipsen Announce $900 Million Licensing Deal for STRO-003 ADC

On April 1, 2024, Sutro Biopharma, a NASDAQ-listed American company, and the renowned French pharmaceutical company Ipsen, entered into a global exclusive licensing agreement. The agreement covers Sutro's investigational ADC (Antibody-Drug Conjugate) candidate, STRO-003. Under the terms of the deal, Ipsen will make an upfront payment of $90 million to Sutro and potentially pay up to $900 million in milestone payments. This is Ipsen's first major investment in the ADC field. STRO-003 is a next-generation ADC targeting ROR1 (Receptor Tyrosine Kinase-Like Orphan Receptor 1). This ADC uses exatecan (iexabepilone) as the payload, delivered through a β-glucuronidase-cleavable linker. In addition to STRO-003, Sutro has other ADC candidates in clinical development, including FRa ADC and CD74 ADC, as well as TF ADC in preclinical stages. The company is also collaborating with Astellas on immunostimulatory ADCs (iADCs) in preclinical research. In the ROR1 ADC space, other notable candidates include CS5001 from LegoChem/Cornerstone, Zilovertamab Vedotin (MK-2140) from Merck/VelosBio, a bispecific antibody-drug conjugate from Bolt Biotherapeutics, and NBE-002 from BI/NBE Therapeutics. According to recent clinical data from Cornerstone, CS5001 has demonstrated promising anti-tumor activity and a favorable safety profile across various solid tumors and hematological malignancies. This transaction not only highlights the immense potential of ADC technology in targeted cancer therapy, but also reflects the intense competition among domestic and international pharmaceutical companies in this field. A thorough analysis of the current clinical and market landscape of ROR1 ADCs will help us better understand the future development trends of innovative medicines.

引进/卖出抗体药物偶联物

2024-06-11

·米内网

【重磅】中美华东1类新药来袭！猛攻1800亿市场

精彩内容近日，中美华东申报的1类新药注射用HDM2005的临床申请获得临床试验默示许可，用于治疗晚期恶性肿瘤，这是公司首个自主研发的抗体药物偶联物(ADC)。米内网数据显示，2023年中国公立医疗机构终端抗肿瘤和免疫调节剂（化学药+生物药）销售额超过1800亿元。注射用HDM2005是由中美华东研发并拥有全球知识产权的1类生物新药，是一款靶向受体酪氨酸激酶样孤儿受体1(ROR1)的抗体偶联药物(ADC)。ROR1是一种典型的肿瘤胚胎蛋白，具有肿瘤细胞特异性，在多种实体瘤和血液瘤中高表达，为潜力ADC靶点。米内网数据显示，目前全球尚无靶向ROR1的ADC获批上市。在研同类药物中，默沙东的MK-2140(VLS-101)进展最快，其弥漫性大B细胞淋巴瘤适应症目前已处于临床III期阶段。2020年11月，默沙东以27.5亿美元收购VelosBio，收获了VLS-101。此外，NBE-002处于II期临床。2020年12月，勃林格殷格翰宣布以最高11.8亿欧元收购NBE-Therapeutics，将NBE-002收入囊中；LCB-71处于I期临床。2020年10月，基石药业以1000万美元的首付款以及最高3.535亿美元里程碑金额获得了该产品在韩国以外的权益。全球部分在研的ROR1 ADC来源：米内网全球新药研发数据库华东医药高度重视创新研发，2023年公司医药工业研发投入(不含股权投资)22.93亿元，同比增长23.67%，其中直接研发支出16.00亿元，同比增长33.74%，占医药工业营收比例为13.1%。在持续的研发创新下，华东医药在抗肿瘤、内分泌和自身免疫三大核心治疗领域均已有全球首创新药(first-in-class)布局，并形成了ADC、GLP-1、外用制剂三大特色研发矩阵，构筑差异化优势。在抗肿瘤领域，华东医药于今年5月提交了化药1类新药迈华替尼片的上市申请，这是一款新型、强效、高选择性、具有口服活性的不可逆EGFR/人表皮生长因子受体-2(HER2)小分子抑制剂，用于EGFR 21号外显子L858R置换突变的局部晚期或转移性NSCLC成人患者的一线治疗。此外，公司引进的治疗卵巢癌的全球首创ADC药物索米妥昔单抗注射液国内上市申请于2023年10月获得受理，用于治疗既往接受过1-3线系统性治疗的叶酸受体α(FRα)阳性的铂类耐药的上皮性卵巢癌、输卵管癌或原发性腹膜癌成年患者。华东医药部分报产且在审的新药来源：米内网中国申报进度（MED）数据库米内网数据显示，2023年中国城市公立医院、县级公立医院、城市社区中心以及乡镇卫生院（简称中国公立医疗机构）终端抗肿瘤和免疫调节剂（化学药+生物药）销售额超过1800亿元。近年来中国公立医疗机构终端抗肿瘤和免疫调节剂销售情况（单位：万元）来源：米内网中国公立医疗机构药品终端竞争格局注：米内网《中国公立医疗机构药品终端竞争格局》，统计范围是：中国城市公立医院、县级公立医院、城市社区中心以及乡镇卫生院，不含民营医院、私人诊所、村卫生室；上述销售额以产品在终端的平均零售价计算。数据统计截至6月11日，如有疏漏，欢迎指正！本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092 【分享、点赞、在看】点一点不失联哦

抗体药物偶联物并购临床2期申请上市引进/卖出

2024-06-10

·药融圈

ROR1 ADC火了，近期付款达6.52亿

▲8月15-16日 NDC2024生物医药创新者峰会扫码立即报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。药融云数据www.pharnexcloud.com监测显示：2024年4月1日，美国纳斯达克上市公司Sutro Biopharma与法国巨头益普生（Ipsen）联合宣布：就Sutro的在研候选抗体偶联药物（ADC）STRO-003达成一项总金额最多高达9亿美元的全球独家授权许可协议。近期付款为9000万美元，约合6.522亿人民币。这是Ipsen首次重仓ADC资产，STRO-003是一款下一代ROR1（受体酪氨酸激酶样孤儿受体1，receptor tyrosine kinase-like orphan receptor 1）靶向ADC新药。该ADC采用exatecan（依喜替康）为有效载荷，β-葡糖醛酸糖苷酶（β-glucuronidase)可裂解连接子。DAR（药物抗体比率）值为8。该公司此外还有临床阶段的FRa ADC候选新药，授权了中国上市公司天士力。CD74 ADC此前授权给了中国新药企业烨辉医药。TF ADC处于临床前阶段。与日本巨头安斯泰来合作的immunostimulatory ADCs (iADCs)同样处于临床前阶段。药融云数据www.pharnexcloud.com监测显示，在做ROR1 ADC的新药企业有：LegoChem/基石药业的CS5001；默沙东/VelosBio（27.5亿美元收购）的Zilovertamab Vedotin (MK-2140,原名 VLS-101)；博锐生物（双特异性抗体偶联药物）;BI/NBE Therapeutics的NBE-002；华东医药等等。其中，基石药业：2024年公布的ASCO海报中首次披露更多CS5001的最新有效性和安全性数据：截至海报数据截止日，已递增至第9剂量水平（156 μg/kg）；仍未观察到DLT，且未达MTD。已观察到的药物相关不良事件大多为1级或2级（评价标准NCI-CTCAE v5.0），表明CS5001针对多线经治的晚期实体瘤和淋巴瘤均能表现出良好的耐受性和安全性。药代动力学数据表明CS5001的暴露量与剂量成正比，且ADC和总抗体的暴露量相似，表明CS5001 ADC在血液循环中具有出色的稳定性。已在多种实体瘤（评价标准RECIST v1.1）和血液肿瘤（评价标准Lugano 2014）中观察到CS5001令人鼓舞的抗肿瘤活性。参考： NMPA/CDE；药融云数据www.pharnexcloud.com； FDA/EMA/PMDA；相关公司公开披露； https://www.sutrobio.com/； https://www.sutrobio.com/news/presentations/； https://www.sutrobio.com/ipsen-and-sutro-biopharma-announce-exclusive-global-licensing-agreement-for-an-adc-targeting-solid-tumors/； https://www.ipsen.com/press-releases/ipsen-and-sutro-biopharma-announce-exclusive-global-licensing-agreement-for-an-adc-targeting-solid-tumors/; 来自法国：特色药企Ipsen（益普生）快速发展中; www.nbe-therapeutics.com; https://nbe-therapeutics.com/newsroom/news-press-releases/2021/nbe-therapeutics-expanded-access-policy-for-nbe-002-a-ror1-targeting-antibody-drug-conjugate； https://www.prnasia.com/story/448228-1.shtml；等等。本文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐 8月重磅XDC峰会推荐【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

抗体药物偶联物引进/卖出ASCO会议并购

100 项与 Zilovertamab vedotin 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
弥漫性大B细胞淋巴瘤	临床3期	美国	默沙东研发（中国）有限公司	2022-01-14
弥漫性大B细胞淋巴瘤	临床3期	加拿大	默沙东研发（中国）有限公司	2022-01-14
弥漫性大B细胞淋巴瘤	临床3期	法国	默沙东研发（中国）有限公司	2022-01-14
弥漫性大B细胞淋巴瘤	临床3期	以色列	默沙东研发（中国）有限公司	2022-01-14
弥漫性大B细胞淋巴瘤	临床3期	意大利	默沙东研发（中国）有限公司	2022-01-14
弥漫性大B细胞淋巴瘤	临床3期	波兰	默沙东研发（中国）有限公司	2022-01-14
弥漫性大B细胞淋巴瘤	临床3期	韩国	默沙东研发（中国）有限公司	2022-01-14
弥漫性大B细胞淋巴瘤	临床3期	泰国	默沙东研发（中国）有限公司	2022-01-14
弥漫性大B细胞淋巴瘤	临床3期	土耳其	默沙东研发（中国）有限公司	2022-01-14
弥漫性大B细胞淋巴瘤	临床3期	英国	默沙东研发（中国）有限公司	2022-01-14

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05144841 (2140-004 \| waveLINE-004 \| MK-2140-004, ASH2023)	临床2期	复发性弥漫性大B细胞淋巴瘤	98	Zilovertamab vedotin 2.5 mg/kg	遞遞齋選鬱憲鑰襯糧遞(衊窪餘醖衊構簾壓遞鏇) = 鏇淵鹹鬱遞鬱顧餘憲鹽壓遞醖鏇醖壓製鏇鬱鏇 (淵鬱獵淵醖窪鏇膚選簾, 19.4 ~ 40.4) 更多	-	2023-12-09
NCT03833180 (waveLINE-001 \| 2140-001, EHA2023)	临床1期	急性髓性白血病 \| 套细胞淋巴瘤 \| 滤泡性淋巴瘤 ... 更多	56	Zilovertamab vedotin	網鏇構鏇積衊餘憲網膚(齋製鹽窪繭衊醖顧醖構) = 遞鑰憲製鏇憲醖構憲糧製襯糧鬱製積積壓襯餘 (繭襯糧構願願淵遞廠網, 2.7 ~ NE) 更多	-	2023-06-08
NCT05144841 (2140-004 \| waveLINE-004 \| MK-2140-004, ASCO2023) 人工标引	临床2期	弥漫性大B细胞淋巴瘤	40	zilovertamab vedotin 2.5 mg/kg	繭選繭願獵繭積願鬱願(鹹齋糧夢鏇齋鑰製簾鬱) = 蓋顧製膚憲夢鬱齋廠夢顧蓋願鹽齋顧繭製艱衊 (鑰願醖繭壓壓範範積繭, 11.9 ~ 54.3) 更多	积极	2023-05-31
NCT03833180 (Waveline-001 \| 2140-001, ASH2022) 人工标引	临床1期	非霍奇金淋巴瘤	54	Zilovertamab vedotin (DLBCL)	鹽製衊遞網繭鏇鬱獵積(觸製構鬱壓糧獵顧鑰網) = 鏇選蓋壓選獵艱艱選鬱繭範膚構願積遞鹽築憲 (築繭窪構憲鑰醖鹽繭蓋, 0.5 ~ 7.0) 更多	积极	2022-11-15
NCT03833180 (Waveline-001 \| 2140-001, ASH2022) 人工标引	临床1期	非霍奇金淋巴瘤	54	Zilovertamab vedotin (MCL)	鹽製衊遞網繭鏇鬱獵積(觸製構鬱壓糧獵顧鑰網) = 網淵製糧餘構廠簾範醖繭範膚構願積遞鹽築憲 (築繭窪構憲鑰醖鹽繭蓋, 4.0 ~ NE) 更多	积极	2022-11-15
NCT03833180 (2140-001, ASH2021) 人工标引	临床1期	非霍奇金淋巴瘤	51	Zilovertamab vedotin	衊艱齋選網衊淵鹹築衊(憲鹽鬱衊繭憲襯顧夢顧) = 鏇齋範鏇構齋鏇窪鬱鏇觸範蓋遞願鹹糧醖選醖 (憲夢窪蓋網遞遞壓獵構 ) 更多	积极	2021-11-05