An Open, Randomized,Positive Control, Multicenter Phase III Clinical Study of SHR A1904 for Injection Compared With Investigator's Choice of Therapy in Claudin18.2 Positive Patients With Second-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

The study evaluated the overall survival (OS) of SHR-A1904 versus investigator-selected treatment in second-line CLDN18.2-positive advanced GC/GEJC patients

开始日期2024-11-10

申办/合作机构

上海恒瑞医药有限公司

NCT06547736 / Not yet recruiting临床2期IIT

A Single-center, Open-label, Exploratory Platform Research on Precision Therapy of Advanced Pancreatic Cancer

The study is being conducted to evaluate the safety, tolerability and efficacy of ADC drugs monotherapy or combination therapy with HRS-4642 in subjects with locally advanced or metastatic pancreatic cancer.

开始日期2024-09-01

申办/合作机构

复旦大学

[+1]

CTR20242710 / Recruiting临床1/2期

HRS-4642联合抗肿瘤药物在晚期实体瘤受试者中的安全性、耐受性及有效性的IB /II期临床研究

评估HRS-4642联合抗肿瘤药物在KRAS G12D突变的晚期实体瘤受试者中的安全性和初步疗效

开始日期2024-08-06

申办/合作机构

江苏恒瑞医药股份有限公司

100 项与 CLDN18.2 相关的临床结果

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100 项与 CLDN18.2 相关的转化医学

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0 项与 CLDN18.2 相关的专利（医药）

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229

项与 CLDN18.2 相关的文献（医药）

2024-12-31·Gut Microbes

Gut microbiota modulate CD8 ⁺ T cell immunity in gastric cancer through Butyrate/GPR109A/HOPX

Article

作者: Ou, Jinzhou ; Li, Guoxin ; Xie, Lang ; Yu, Xiang ; Shen, Guodong ; Zhao, Cuiyin ; Ren, Yingxin ; Liang, Junxian ; Chen, Zhian ; Zou, Zhaowei ; Li, Zhenyuan ; Hu, Yanfeng ; Wang, Lingzhi

The gut microbiota and Short-chain fatty acids (SCFAs) can influence the progression of diseases, yet the role of these factors on gastric cancer (GC) remains uncertain. In this work, the analysis of the gut microbiota composition and SCFA content in the blood and feces of both healthy individuals and GC patients indicated that significant reductions in the abundance of intestinal bacteria involved in SCFA production were observed in GC patients compared with the controls. ABX mice transplanted with fecal microbiota from GC patients developed more tumors during the induction of GC and had lower levels of butyric acid. Supplementation of butyrate during the induction of gastric cancer along with H. pylori and N-methyl-N-nitrosourea (MNU) in WT in GPR109A^-/-mice resulted in fewer tumors and more IFN-γ⁺ CD8⁺ T cells, but this effect was significantly weakened after knockout of GPR109A. Furthermore, In vitro GC cells and co-cultured CD8⁺ T cells or CAR-Claudin 18.2⁺ CD8⁺ T cells, as well as in vivo tumor-bearing studies, have indicated that butyrate enhanced the killing function of CD8⁺ T cells or CAR-Claudin 18.2⁺ CD8⁺ T cells against GC cells through G protein-coupled receptor 109A (GPR109A) and homologous domain protein homologous box (HOPX). Together, these data highlighted that the restoration of gut microbial butyrate enhanced CD8⁺ T cell cytotoxicity via GPR109A/HOPX, thus inhibiting GC carcinogenesis, which suggests a novel theoretical foundation for GC management against GC.

2024-11-01·British Journal of Pharmacology

Dual targeting chimeric antigen receptor cells enhance antitumour activity by overcoming T cell exhaustion in pancreatic cancer

Article

作者: Zonghai, Li ; Yifan, Liu ; Hua, Jiang ; Bizhi, Shi ; Xiaoli, Hu ; Yiwei, Dong ; Yansha, Sun ; Min, Zhou ; Ruixin, Sun

Background and PurposeAlthough our previous data indicated that claudin 18 isoform 2 (CLDN18.2)‐targeted chimeric antigen receptor (CAR) T cells displayed remarkable clinical efficacy in CLDN18.2‐positive gastric cancer, their efficacy is limited in pancreatic ductal adenocarcinoma (PDAC). The tumour microenvironment (TME) is one of the main obstacles to the efficacy of CAR‐T and remodelling the TME may be a possible way to overcome this obstacle. The TME of PDAC is characterized by abundant cancer‐related fibroblasts (CAFs), which hinder the infiltration and function of CLDN18.2‐targeted CAR‐T cells. The expression of fibroblast activation protein alpha (FAP) is an important feature of active CAFs, providing potential targets for eliminating CAFs.Experimental ApproachIn this study, we generated 10 FAP/CLDN 18.2 dual‐targeted CAR‐T cells and evaluated their anti‐tumour ability in vitro and in vivo.Key ResultsCompared with conventional CAR‐T cells, some dual‐targeted CAR‐T cells showed improved therapeutic effects in mouse pancreatic cancers. Further, dual‐targeted CAR‐T cells with better anti‐tumour effect could suppress the recruitment of myeloid‐derived suppressor cells (MDSCs) to improve the immunosuppressive TME, which contributes to the survival of CD8+ T cells. Moreover, dual‐targeted CAR‐T cells reduced the exhaustion of T cells in transforming TGF‐β dependent manner.Conclusion and ImplicationsThe dual‐targeted CAR‐T cells obtained enhancement of T effector function, inhibition of T cell exhaustion, and improvement of tumour microenvironment. Our findings provide a theoretical rationale for dual‐targeted FAP/CLDN 18.2 CAR‐T cells therapy in PDAC.

2024-11-01·Journal of Pharmacological Sciences

Effect of antiemetics on zolbetuximab-induced gastric injury and emesis in ferrets

Article

作者: Kajikawa, Satoru ; Suzuki, Hiroshi ; Weng, Jane ; Haggerty, Gillian ; Sawamoto, Taiji ; Nakazawa, Taisuke ; Kinugasa, Fumitaka ; Yamanaka, Yosuke ; Ugawa, Tohru ; Nagata, Masanori ; Akuzawa, Shinobu ; Fushiki, Hiroshi

Claudin-18 splice variant 2 (CLDN18.2), a tight junction protein, is a highly cell type-specific antigen that is expressed by differentiated gastric mucosa cells. The expression of CLDN18.2 in gastric mucosa cells may be retained upon malignant transformation and is displayed on the surface of several tumors, including gastric/gastroesophageal junction adenocarcinoma. Zolbetuximab is a genetically engineered, highly purified chimeric (mouse/human IgG1) antibody directed against CLDN18.2. Nausea and vomiting were observed as adverse events of zolbetuximab. To investigate the mechanism of nausea and vomiting in humans, we evaluated emesis (retching and vomiting) and conducted histopathologic assessment in ferrets after the administration of zolbetuximab. Emesis was frequently observed in all ferrets treated with zolbetuximab in the first hour after administration. Histopathologic assessment revealed the surface of the gastric mucosa was the primary site of emesis-associated tissue damage. The effect of antiemetics (dexamethasone, ondansetron, fosaprepitant, and olanzapine) on emesis induced by zolbetuximab was investigated. Fosaprepitant showed suppressive effects on emesis, and use of dexamethasone or concomitant use of fosaprepitant with other antiemetics tended to alleviate gastric tissue damage. The onset of emesis in humans receiving zolbetuximab may be associated with damage in the gastric mucosa, and antiemetics may mitigate gastrointestinal adverse events.

3,509

项与 CLDN18.2 相关的新闻（医药）

2024-10-31

·医药笔记

安进：第2款实体瘤CD3双抗，Xaluritamig将启动前列腺癌三期临床

▎Armstrong 2024年10月30日，安进发布三季度财报，介绍了研发管线的最新进展，肿瘤业务板块中重点提到STEAP1/CD3双抗Xaluritamig将在本季度启动紫杉醇后线的前列腺癌三期临床试验。 Xaluritamig采用Xencor的XmAb 2+1技术设计，目前处于一期临床阶段，意味着安进将直接推进到三期临床。 Xencor还有其他多款实体瘤CD3双抗在推进中，覆盖靶点包括ENPP3、Claudin6、B7H3等，均采用XmAb 2+1技术。今年AACR会议上，安进披露了Xaluritamig的一期临床数据，PSA和RECIST评估疗效数据如下，PSA50为49%，PSA90为28%。以RECIST评估，高剂量组ORR为41%，DCR为79%。总结作为最老牌的biotech，安进研发管线中还有多哥潜在爆款产品，除了前述两款实体瘤CD3双抗，还有自免领域的OX40抗体Rocatinlimab，代谢领域的GIPR抗体融合GLP-1分子MariTide等。 Armstrong技术全梳理系列 GPRC5D靶点全梳理； CD40靶点全梳理； CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向； Claudin 6靶点全梳理； Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇； CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理； Ambrx技术全梳理； Vir Biotech技术全梳理； Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理； Momenta技术全梳理； NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

AACR会议临床3期财报抗体药物偶联物

2024-10-31

·医药笔记

安进：CD3/CD19双抗启动狼疮肾炎二期临床

▎Armstrong 2024年10月30日，安进发布三季度三包，营收81.51亿美元，同比增长23%，扣除收购Horizon的影响，营收增长8%。肿瘤业务板块，CD3/CD19双抗Blincyto三季度销售额3.27亿美元，同比增长49%，小细胞肺癌的DLL3/CD3双抗Imdelltra首季度销售额3600万美元。 Blincyto正在探索皮下剂型，B-ALL的1/2期临床已经完成入组，预计2025年下半年推进到二期注册临床。安进正在积极开拓自免领域，CD3/CD19双抗和CD19单抗已经启动狼疮肾炎的二期临床试验。 2a期临床计划入组50例，其中CD3/CD19双抗采用皮下注射剂型。安全性终点观察52周，疗效终点观察12周和24周。总结 Blincyto为全球首个也是唯一一个获批上市的CD3/CD19双抗，这一波自免浪潮中第一个推进到二期临床。Cullinan刚刚启动1b期临床，计划入组24例狼疮患者。默沙东7亿美元引进了同润生物的CD3/CD19双抗，葛兰素史克8.5亿美元引进恩沐生物的CD3/CD19/CD20双抗。Xencor宣布CD3/CD20双抗、CD3/CD19双抗转战自免领域。Candid收购了嘉和生物的CD3/CD20双抗、岸迈生物的CD3/BCMA双抗。 Armstrong技术全梳理系列 GPRC5D靶点全梳理； CD40靶点全梳理； CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向； Claudin 6靶点全梳理； Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇； CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理； Ambrx技术全梳理； Vir Biotech技术全梳理； Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理； Momenta技术全梳理； NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

临床2期并购临床1期抗体药物偶联物

2024-10-30

·Armstrong生物药资讯

礼来：替尔泊肽前三季度大卖110亿美元

▎Armstrong 2024年10月30日，礼来发布三季度财报，前三季度营业收入315亿美元，同比增长27%，净利润61.8亿美元。前三季度，替尔泊肽降糖版Moujaro销售额80.10亿美元，去年同期为29.58亿美元，替尔泊肽减重版Zepbound销售额30.18亿美元。替尔泊肽合计销售额110亿美元，预计全年超过160亿美元。替尔泊肽去年11月份上市以来放量迅速，累计处方患者超过60万人。降糖版Mounjaro三季度与二季度销售额基本持平，美国处方份额约30%。总结诺和诺德司美格鲁肽今年上半年销售额为130亿美元，替尔泊肽正在快速抢占市场，与司美格鲁肽的差距快速缩小。横向对比，Keytruda今年上半年销售额142亿美元，未来新的药王争夺大概率会在司美格鲁肽、替尔泊肽中间产生。 Armstrong技术全梳理系列 GPRC5D靶点全梳理； CD40靶点全梳理； CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向； Claudin 6靶点全梳理； Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇； CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理； Ambrx技术全梳理； Vir Biotech技术全梳理； Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理； Momenta技术全梳理； NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

财报抗体药物偶联物