A Phase 1/2, Open-label, Dose-escalation, Dose-optimization and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Therapeutic Activity of GI-101/GI-101A as a Single Agent and in Combination With Pembrolizumab or Lenvatinib in Patients With Advanced or Metastatic Solid Tumors (Keynote B59)

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-101/GI-101A as a single agent or in combination with pembrolizumab or lenvatinib over a range of advanced and/or metastatic solid tumors.

开始日期2021-08-02

申办/合作机构

GI Innovation, Inc.

[+1]

100 项与 SIM-323 相关的临床结果

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100 项与 SIM-323 相关的转化医学

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100 项与 SIM-323 相关的专利（医药）

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项与 SIM-323 相关的文献（医药）

2012-12-01·Journal of translational medicine2区 · 医学

Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells

2区 · 医学

ArticleOA

作者: Aladar A Szalay ; Huiqiang Wang ; Boris R Minev ; Nanhai G Chen

Abstract:

Background:

Recent data suggest that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are responsible for relapses after apparently curative therapies have been undertaken. Hence, novel cancer therapies will be needed to test for both tumor regression and CSC targeting. The use of oncolytic vaccinia virus (VACV) represents an attractive anti-tumor approach and is currently under evaluation in clinical trials. The purpose of this study was to demonstrate whether VACV does kill CSCs that are resistant to irradiation and chemotherapy.

Methods:

Cancer stem-like cells were identified and separated from the human breast cancer cell line GI-101A by virtue of increased aldehyde dehydrogenase 1 (ALDH1) activity as assessed by the ALDEFLUOR assay and cancer stem cell-like features such as chemo-resistance, irradiation-resistance and tumor-initiating were confirmed in cell culture and in animal models. VACV treatments were applied to both ALDEFLUOR-positive cells in cell culture and in xenograft tumors derived from these cells. Moreover, we identified and isolated CD44+CD24+ESA+cells from GI-101A upon an epithelial-mesenchymal transition (EMT). These cells were similarly characterized both in cell culture and in animal models.

Results:

We demonstrated for the first time that the oncolytic VACV GLV-1h68 strain replicated more efficiently in cells with higher ALDH1 activity that possessed stem cell-like features than in cells with lower ALDH1 activity. GLV-1h68 selectively colonized and eventually eradicated xenograft tumors originating from cells with higher ALDH1 activity. Furthermore, GLV-1h68 also showed preferential replication in CD44+CD24+ESA+cells derived from GI-101A upon an EMT induction as well as in xenograft tumors originating from these cells that were more tumorigenic than CD44+CD24-ESA+cells.

Conclusions:

Taken together, our findings indicate that GLV-1h68 efficiently replicates and kills cancer stem-like cells. Thus, GLV-1h68 may become a promising agent for eradicating both primary and metastatic tumors, especially tumors harboring cancer stem-like cells that are resistant to chemo and/or radiotherapy and may be responsible for recurrence of tumors.

2011-01-01·Cancer gene therapy2区 · 医学

Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA

2区 · 医学

Article

作者: J M von Hof ; L F Tietze ; M Hess ; I Gentschev ; J B Sturm ; N Chen ; C M Seubert ; B Krewer ; A A Szalay ; U Donat ; J Stritzker

Breast cancer is the most common cause of cancer-related death worldwide, thus remaining a crucial health problem among women despite advances in conventional therapy. Therefore, new alternative strategies are needed for effective diagnosis and treatment. One approach is the use of oncolytic viruses for gene-directed enzyme prodrug therapy. Here, the lacZ-carrying vaccinia virus (VACV) strain GLV-1h68 was used in combination with a β-galactosidase-activatable prodrug derived from a seco-analog of the natural antibiotic duocarmycin SA. Tumor cell infection with the VACV strain GLV-1h68 led to production of β-galactosidase, essential for the conversion of the prodrug to the toxic compound. Furthermore, drug-dependent cell kill and induction of the intrinsic apoptosis pathway in tumor cells was also observed on combination therapy using the prodrug and the GLV-1h68 strain, despite the fact that VACV strains encode antiapoptotic proteins. Moreover, GI-101A breast cancer xenografts were effectively treated by the combination therapy. In conclusion, the combination of a β-galactosidase-activatable prodrug with a tumor-specific vaccinica virus strain encoding this enzyme, induced apoptosis in cultures of the human GI-101A breast cancer cells, in which a synergistic oncolytic effect was observed. Moreover, in vivo, additional prodrug treatment had beneficial effects on tumor regression in GLV-1h68-treated GI-101A-xenografted mice.

2008-06-01·Life sciences3区 · 医学

Identification of HDM2 as a regulator of VEGF expression in cancer cells

3区 · 医学

Article

作者: Rajiv Rose ; Madhusudhanan Narasimhan ; Jason A. Zell ; Ramugounder Ramakrishnan ; Appu Rathinavelu

Overexpression of vascular endothelial growth factor (VEGF) and the extent of neoangiogenesis are closely correlated with tumor development and cancer metastases. To assess whether VEGF mediated angiogenesis is regulated by HDM2, we treated the GI-101A and HL-60 cells with HDM2 gene specific antisense phosphorothioate oligodeoxynucleotide (AS5). The antisense treatment resulted in a significant reduction of both basal as well as phorbol 12,13-dibutyrate (PDB) and Diethylstilbestrol (DES) induced VEGF mRNA and protein expressions. Furthermore, when the Human Umbilical Vein Endothelial Cells (HUVECs) were exposed to medium obtained from AS5 transfected GI-101A and HL-60 cells, the angiogenesis was significantly reduced compared to the controls in the in vitro angiogenesis assay. On the contrary, the medium obtained from PDB treated cells that expressed HDM2 and VEGF at a higher level showed an increase in the tube formation by HUVEC. Thus, our present study suggests that modulation of HDM2 expression could play an important role in tumor angiogenesis and the metastatic process via transcriptional regulation of VEGF.

项与 SIM-323 相关的新闻（医药）

2025-12-29

·药事纵横

先声药业，步入BD快车道

12月22日，先声药业宣布与Ipsen签订独家授权许可协议。根据该协议条款，Ipsen将获得靶向LRRC15的抗体药物偶联物（ADC）SIM0613在大中华区以外地区的全球独家开发、生产及商业化权利。先声药业有权收取最高达10.6亿美元的款项，其中包括4500万美元的首付款，以及研发、监管及商业化里程碑付款，另可收取分级销售特许权使用费。SIM0613是一种靶向富含亮氨酸重复序列的蛋白15（LRRC15）的新型ADC，目前处于临床前阶段。 2025年，先声药业三款多抗及ADC产品陆续成功授权，跻身BD的第一梯队。作为一家老牌Pharma，先声药业上演了一出教科书般的由仿到创转型，真正实现了“为患者而生”的企业使命。（一）业绩稳健，创新药收入占比持续提升业绩稳健，收入和净利润快速提升。2025年上半年，先声药业实现收入35.85亿元，同比增长15.1%。经调整净利润达6.5亿元，同比增长21.1%。收入和净利润的快速提升源于创新药的快速放量。一方面，先必新舌下片于2024年12月获批上市，与先必新序贯治疗，延长卒中患者DOT；另一方面，恩立妥（西妥昔单抗β）与科赛拉（曲拉西利）顺利纳入2024年国家医保目录，准入提速后带来患者可及性的大幅提升。随着多款创新药的不断落地并纳入国家医保目录，公司创新药占比逐步提升。2025年上半年，公司创新药占比达77.4%，较2024年占比提升3.1%。放眼未来，公司创新药占比有望持续提升，多款创新药产品于2025年逐步落地，2025年6月，用于治疗失眠的科唯可®（盐酸达利雷生片）获NMPA批准上市，且未被作为精神药品管制；同月，恩泽舒®（注射用苏维西塔单抗）获NMPA批准上市，且成功纳入2025年国家医保目录，未来放量可期。随着抗流感新药玛氘诺沙韦和治疗特应性皮炎的乐德奇拜单抗分别于2025年3月和2025年7月NDA获NMPA受理，公司创新药梯队愈发完善。图：先声药业2020-2025H1创新药收入占比数据来源：先声药业宣传资料（二） BD持续落地，创新转型加速尽管先声药业的创新药占比在2021年已超过50%达到62.3%，但以先必新、恩度、艾得辛等产品为核心的创新药并未受到资本市场的认可，在过去很长一段时间内，先声药业仍背负着传统企业的名号。近年来，随着康方生物、荣昌生物等创新药企业的崛起，与仿制药的估值桎梏形成鲜明对比的，是创新药企的价值重估浪潮，ADC、双/多抗等药物引领着产业估值快速提升。基于此，先声药业快速转型，投身入ADC、TCE等产业趋势产品的研发中。在这一大背景下，BD则是验证企业研发实力的最好背书，尤其是与MNC企业的授权合作。 2025年，可谓是先声药业创新研发开花结果的关键一年，先后三款创新品种成功授权出海，涉及两款ADC产品和一款三抗产品，分别是SIM0500（CD3/BCMA/GPRC5D）、SIM0505 (CDH6-ADC）和SIM0613（LRRC15 ADC）。（1）SIM0500（CD3/BCMA/GPRC5D）是一种靶向GPRC5D/BCMA/CD3的人源化三特异性抗体，由先声再明专有的T细胞衔接器多特异性抗体平台研发。2025年1月，先声药业与艾伯维（AbbVie）就SIM0500开发达成合作，根据协议条款，先声再明将从艾伯维收取首付款，以及最高10.55亿美金的选择性权益付款和里程碑付款。先声再明将额外获得基于该产品在大中华区以外地区净销售额的分级特许权使用费。 GPRC5D/BCMA/CD3三抗在多发性骨髓瘤的疗效已得到验证。强生的JNJ-79635322在2025年ASH上更新了Ⅰ期完整数据，数据显示，中位随访15个月时，JNJ-79635322（100mg，Q4W）组在未接受过BCMA/GPRC5D靶向疗法治疗的患者（n=27），ORR达到了100%，CR率达77.8%，PFS达到12个月的患者比例高达96.3%。安全性上，未发生三级及以上CRS，整体安全性可控。基于优异的临床数据，强生已于12月启动JNJ-79635322的首个III期临床试验（Trilogy-4）。图：先声药业就SIM0500与艾伯维达成合作数据来源：先声药业宣传资料（2）SIM0505（CDH6 ADC）由先声再明研发的一款靶向CDH6（钙粘蛋白-6或K-钙粘蛋白）的新型ADC。其独特的结合表位对肿瘤抗原的亲和力高于同类候选药物。SIM0505采用了先声再明专有的TOPO异构酶1抑制剂(TOPOi)有效载荷，在具有强抗肿瘤活性的同时，具有较高的系统清除率，从而扩大治疗窗口。 2025年6月，先声再明与NextCure就SIM0505达成战略合作，先声药业获得首付1500万美元外加里程碑高至7.45亿美元，及NextCure上市公司股权；还将获得基于再明ADC平台和NextCure抗体平台开发的新靶点ADC的大中华区权益。 CDH6 ADC近年来频频授权。2022年6月，OnCusp Therapeutics与普众发现就AMT-707达成合作授权，OnCusp Therapeutics获得AMT-707在大中华区以外的全球独家开发和商业化权利，普众发现则获得预付款、里程碑付款及特许权使用费。‌2023年10月，默沙东与第一三共就后者的三个ADC候选药物达成了全球开发和商业化协议，其中包括DS-6000（CDH6 ADC）。目前，SIM0505已完成首批5例患者的给药，分为1.6 mpk与3.2 mpk两个剂量组。早期数据表明，1.6 mpk低剂量组已有患者达到部分缓解（PR），且整个队列尚未观察到任何间质性肺病（ILD）或≥3级治疗相关不良事件（TEAE）。图：SIM0505 Ⅰ期初步临床数据数据来源：先声药业宣传资料（3）SIM0613是一种靶向富含亮氨酸重复序列的蛋白15（LRRC15）的新型ADC。12月，先声再明与法国益普生（Ipsen）就SIM0613达成大中华区以外全球权益的独家对外授权许可协议。 LRRC15在肉瘤、胶质母细胞瘤和黑色素瘤等多种间充质肿瘤中高表达，发挥促进肿瘤转移的作用。此外，LRRC15 在多种肿瘤的癌症相关成纤维细胞 (CAF) 中高表达，促进免疫排斥和免疫抑制肿瘤微环境 (TME)的形成。这些使得 LRRC15 成为肿瘤治疗中一个颇具吸引力的靶点。目前，全球尚无LRRC15 ADC进入临床阶段。除了先声药业的SIM0613成功携手益普生外，2025年1月，再鼎医药与宜联生物达成战略合作，共同推进ZL-6201（LRRC15 ADC）的临床开发。（三）小结近年来，先声药业的创新转型十分成功，多款ADC、多款药物授权出海，成功驱动公司股价快速上涨。放眼公司早期产品管线，仍有十余款多抗、ADC产品具有不俗的授权潜力，包括SIM0237（PDL1/IL15v）、SIM0686（FGFR2b ADC）、SIM0323（CD80/IL2）等。优异的商业化能力叠加强大的研发实力，期待公司发展更上一层楼。立即扫码加入药事纵横交流群

抗体药物偶联物引进/卖出上市批准

2025-01-22

·PRNewswire

GI Innovation-LaNova Medicines Signs MOU for GI-102 + ADC Pancreatic Cancer Combination Therapy

SEOUL, South Korea, Jan. 22, 2025 /PRNewswire/ -- GI Innovation (KQ:358570) announced that it signed a Memorandum of Understanding (MOU) with LaNova Medicines (LaNova) for the development of GI-102 and ADC pancreatic cancer combination therapy. This MOU was held on January 15th, local time, during JP Morgan Healthcare Conference (San Francisco, USA). Continue Reading From the left, Rhee Byung-geon, Chairman and CEO of GI Innovation, Dr. Crystal Quin, CEO of LaNova Medicines, and Jang Myoung-ho, CSO of GI Innovation. (Source: GI Innovation) The two companies have been conducting combination therapy study of the immuno-oncology drug GI-102 and ADC LM-302 targeting Claudin18.2 and recently observed excellent anticancer activity in a preclinical pancreatic cancer model. Both substances are in the clinical stage. GI-102 has completed phase 1 clinical trial in the US and Korea and can quickly enter phase 2. LM-302 is currently in phase 3 clinical trial for 3L and above gastric cancer in China. Pancreatic cancer has no approved immunotherapy, and the only approved treatment is a chemotherapy cocktail, but its treatment efficacy is low and its toxicity is high. Through this agreement, both companies will conduct clinical trial targeting patients with metastatic pancreatic cancer. Dr. Myoung Ho Jang, CSO said, "We are delighted to be conducting a combination study with LaNova, which is recognized by global pharma companies. LaNova's ADC, which directly destroys tumor cells to increase the response rate, and GI-102, which can enhance immune memory to increase overall survival, are expected to be a combination therapy that can change the pancreatic cancer treatment paradigm." "GI-102 exemplifies GI Innovation's robust R&D capabilities in immunotherapy. We are excited to explore its combination with LaNova's Claudin18.2 ADC, LM-302, which holds the potential to provide a novel therapeutic option for pancreatic cancer patients" Dr. Crystal Qin, LaNova CEO emphasized. About GI Inovation GI Innovation, a KOSDAQ-listed biotech, pioneers fusion protein drugs for cancer and allergies. Since 2017, it secured $230 million through funding rounds, IPO, and licensing deals for preclinical and clinical assets. Leveraging global partnerships for rapid development, the leading programs include immuno-oncology assets GI-101, subcutaneous form GI-102, and anti-allergy asset GI-301, metabolic immuno-oncology asset GI-108 alongside other innovative programs. SOURCE GI Innovation WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期免疫疗法临床2期抗体药物偶联物上市批准

2024-10-25

·药研网

先声药业癌症新药CDH6 ADC申报临床

10月25日，CDE官网显示，先声药业旗下先祥医药申报的1类新药—注射用SIM0505的临床试验申请获得NMPA受理。据其官网，SIM0505为一款 CDH6 ADC，是先声药业申报的首款ADC新药，也是第2款国产CDH6 ADC。根据管线信息，先声药业SIM0686（FGFR2b-ADC）、SIM0323（CD80/IL-2双功能融合蛋白）等抗肿瘤管线也处于临床前阶段。 2024年8月22日，先声药业旗下抗肿瘤创新药公司先声再明宣布，其自主研发的抗肿瘤候选药物－DNA聚合酶θ（Polθ）小分子抑制剂SIM0508已获得国家药监局批准开展药物临床试验，拟用于治疗晚期实体瘤。 End 声明：本公众号所有发文章(包括原创及转载文章)系出于传递更多信息之目的，且注明来源和作者。本公众号欢迎分享朋友圈或大群，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载/商务/投稿 | 联系微信15618157102（sum_Gmi）商务合作稿件征集点击了解详情往期回顾 1 8月 | 高达22家药企裁员 2 国产首款四价HPV疫苗拟纳入优先审评 3 3. 7亿美元!今年规模最大的生物医药融资诞生

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100 项与 SIM-323 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床2期	美国	GI Innovation, Inc.	2021-08-02
晚期恶性实体瘤	临床2期	韩国	GI Innovation, Inc.	2021-08-02
转移性实体瘤	临床2期	美国	GI Innovation, Inc.	2021-08-02
转移性实体瘤	临床2期	韩国	GI Innovation, Inc.	2021-08-02
肾细胞癌	临床2期	美国	GI Innovation, Inc.	2021-08-02
肾细胞癌	临床2期	韩国	GI Innovation, Inc.	2021-08-02
鳞状非小细胞肺癌	临床2期	美国	GI Innovation, Inc.	2021-08-02
鳞状非小细胞肺癌	临床2期	韩国	GI Innovation, Inc.	2021-08-02
膀胱尿路上皮癌	临床2期	美国	GI Innovation, Inc.	2021-08-02
膀胱尿路上皮癌	临床2期	韩国	GI Innovation, Inc.	2021-08-02

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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


NCT04977453 (Keynote-B59, SITC2023)	临床1/2期	晚期恶性实体瘤	25	GI-101 (CD80-IL2v) + Pembrolizumab	衊鹹壓鏇蓋獵襯糧願鬱(遞襯網夢窪夢遞鑰夢廠) = 28%, 24% 製餘鏇鹽糧構糧願遞觸 (蓋蓋獵願觸製製積鑰淵 ) 更多	积极	2023-11-02
NCT04977453 (GII-101-P101, ESMO 12023 \| ESMO 22023) 人工标引	临床1/2期	晚期恶性实体瘤	57	GI-101	積觸構憲築壓襯醖網餘(範鑰窪顧齋夢遞壓願製) = 顧鹽廠鹽淵築壓襯繭蓋壓願糧醖遞糧網憲構醖 (簾醖窪齋積壓憲壓齋鏇 ) 更多	积极	2023-10-23
				GI-101 (MSS CRC with liver metastasis)	膚淵鹹糧製鏇鏇築選窪(顧膚構範廠衊築範鹽糧) = 簾鏇簾顧醖遞餘範衊願觸蓋醖鹽鹽憲簾蓋齋積 (壓廠窪醖膚願壓鏇夢願 )
NCT04977453 (GII-101-P101, SITC 12022 \| SITC 22022) 人工标引	临床1/2期	转移性实体瘤	25	GI-101	糧繭鹽繭夢衊憲衊鏇鬱(膚繭觸願構鏇鏇鹹壓築) = No dose-limiting toxicities up to 0.15 mg/kg were reported with planned dose level of 0.002~0.6 mg/kg. 夢壓餘糧遞鹹願鏇蓋醖 (醖繭選選遞積積觸積夢 )	积极	2022-11-01
				pembrolizumab+GI-101