A Phase 1b/2, Safety Lead-in and Dose-Expansion, Open Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Activity of Ivosidenib in Combination With Durvalumab and Gemcitabine/Cisplatin as First-line Therapy in Participants With Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

The objective of this study is to investigate the safety, tolerability and preliminary activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin as first-line therapy in participants with locally advanced, unresectable or metastatic cholangiocarcinoma with an IDH1 mutation. The study will begin with a safety lead-in phase (Phase 1b study) to determine the recommended combination dose (RDC) and then will transition to an expansion phase (Phase 2 study) to assess the clinical activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin at the RCD. During the treatment period participants will have study visits on days 1, 8, and 15 of Cycle 1, on days 1 and 8 of Cycle 2 to 8, and on day 1 of each additional cycle. Cycles 1 through 8 are 21 day cycles, and each following cycle is 28 days. Approximately 30 days and 90 days after treatment has ended, safety follow-up visits will occur and then participants will be followed for survival every 3 months. Study visits may include blood tests, ECG, vital signs, and a physical examination.

开始日期2024-12-16

申办/合作机构

Institut de Recherches Intern Servier

NCT06488222 / Not yet recruiting临床2期IIT

Intravesical Gemcitabine and Docetaxel for Low Grade Intermediate Risk Bladder Cancer

Bladder cancer is the 8th most common cancer in the UF Health Cancer Center catchment area and the 7th most common cancer presenting to UFHealth. Most newly diagnosed cases are stage I bladder cancer, which is defined by having no deep muscle invasion and no evidence of disease beyond the bladder. The current use in BCG (Bacillus Calmette-Guerin) refractory disease and the ongoing evaluation in BCG naïve high-risk disease support evaluation of intravesical gemcitabine and docetaxel in decreasing disease recurrence in intermediate risk stage I bladder cancer.
This study will investigate the efficacy and subject compliance with treatment of low grade intermediate risk bladder cancer with intravesical gemcitabine and docetaxel.

开始日期2024-10-01

申办/合作机构

University of Florida

NCT06227065 / Not yet recruiting临床2期IIT

Precise Neoadjuvant Chemoresection of Low Grade NMIBC Guided by Drug Screens in Patient Derived Organoidst: A Single Center, Open-label, Phase II Trial

Based on the unmet clinical need to reduce invasiveness of treatment of low grade NMIBC, the investigators conduct this prospective, open label, single arm and single center phase II trial. The investigators aim to use drug screens in PDOs to guide neoadjuvant intravesical instillation therapy with either Epirubicin, Mitomycin C, Gemcitabine or Docetaxel to achieve chemoresection NMIBC.

开始日期2024-10-01

申办/合作机构

University of Bern

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100 项与吉西他滨相关的转化医学

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100 项与吉西他滨相关的专利（医药）

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18,555

项与吉西他滨相关的文献（医药）

2024-05-01·British journal of pharmacology

Expression of fibroblast growth factor receptor 1 correlates inversely with the efficacy of single‐agent fibroblast growth factor receptor‐specific inhibitors in pancreatic cancer

Article

作者: Roy Chaudhuri, Tista ; Straubinger, Robert M ; Ma, Wen Wee ; Qu, Jun ; Perri, Jonathan ; Lin, Qingxiang ; Kandel, Eugene S ; Serratore, Andrea

Abstract:

Background and Purpose:

Elevated fibroblast growth factor receptor (FGFR) activity correlates with pancreatic adenocarcinoma (PDAC) progression and poor prognosis. However, its potential as a therapeutic target remains largely unexplored.

Experimental Approach:

The mechanisms of action and therapeutic effects of selective pan‐FGFR inhibitors (pan‐FGFRi) were explored using in vitro and in vivo PDAC models ranging from gemcitabine‐sensitive to highly gemcitabine‐resistant (GemR). Gain‐/loss‐of‐function investigations were employed to define the role of individual FGFRs in cell proliferation, migration, and treatment response and resistance.

Results:

The pan‐FGFRi NVP‐BGJ398 significantly inhibited cell proliferation, migration, and invasion, and downregulated key cell survival‐ and invasiveness markers in multiple PDAC cell lines. Gemcitabine is a standard‐of‐care for PDAC, but development of resistance to gemcitabine (GemR) compromises its efficacy. Acquired GemR was modelled experimentally by developing highly GemR cells using escalating gemcitabine exposure in vitro and in vivo. FGFRi treatment inhibited GemR cell proliferation, migration, GemR marker expression, and tumour progression. FGFR2 or FGFR3 loss‐of‐function by shRNA knockdown failed to decrease cell growth, whereas FGFR1 knockdown was lethal. FGFR1 overexpression promoted cell migration more than proliferation, and reduced FGFRi‐mediated inhibition of proliferation and migration. Single‐agent FGFRi suppressed the viability and growth of multiple patient‐derived xenografts inversely with respect to FGFR1 expression, underscoring the influence of FGFR1‐dependent tumour responses to FGFRi. Importantly, secondary data analysis showed that PDAC tumours expressed FGFR1 at lower levels than in normal pancreas tissue.

Conclusions and Implications:

Single‐agent FGFR inhibitors mediate selective, molecularly‐targeted suppression of PDAC proliferation, and their effects are greatest in PDAC tumours expressing low‐to‐moderate levels of FGFR1.

2024-04-01·International journal of radiation oncology, biology, physics

Differential Sensitivity to Ionizing Radiation in Gemcitabine-Resistant and Paclitaxel-Resistant Pancreatic Cancer Cells

Article

作者: McDonnell, Liam A ; Mantini, Giulia ; Ali, Mahsoem ; Schmidt, Thomas ; Sminia, Peter ; Finamore, Francesco ; Frampton, Adam E ; Giovannetti, Elisa ; Bergonzini, Cecilia ; Gregori, Alessandro ; Rodrigues, Stephanie M Fraga ; Danen, Erik H ; Che, Pei Pei ; Slotman, Ben J

PURPOSE:

Chemoresistance remains a major challenge in treating pancreatic ductal adenocarcinoma (PDAC). Although chemoradiation has proven effective in other tumor types, such as head and neck squamous cell carcinoma, its role in PDAC and effect on acquired chemoresistance have yet to be fully explored. In this study, we investigated the sensitivity of gemcitabine-resistant (GR) and paclitaxel-resistant (PR) PDAC cells to ionizing radiation (IR) and their underlying mechanisms.

METHODS AND MATERIALS:

GR and PR clones were generated from PANC-1, PATU-T, and SUIT2-007 pancreatic cancer cell lines. Cell survival after radiation was assessed using clonogenic assay, sulforhodamine B assay, apoptosis, and spheroid growth by bioluminescence. Radiation-induced DNA damage was assessed using Western blot, extra-long polymerase chain reaction, reactive oxygen species production, and immunofluorescence. Autophagy and modulation of the Hippo signaling pathway were investigated using proteomics, Western blot, immunofluorescence, and reverse-transcription quantitative polymerase chain reaction.

RESULTS:

In both 2- and 3-dimensional settings, PR cells were more sensitive to IR and showed decreased β-globin amplification, indicating more DNA damage accumulation compared with GR or wild-type cells after 24 hours. Proteomic analysis of PR PATU-T cells revealed that the protein MST4, a kinase involved in autophagy and the Hippo signaling pathway, was highly downregulated. A differential association was found between autophagy and radiation treatment depending on the cell model. Interestingly, increased yes-associated protein nuclear localization and downstream Hippo signaling pathway target gene expression were observed in response to IR.

CONCLUSIONS:

This was the first study investigating the potential of IR in targeting PDAC cells with acquired chemoresistance. Our results demonstrate that PR cells exhibit enhanced sensitivity to IR due to greater accumulation of DNA damage. Additionally, depending on the specific cellular context, radiation-induced modulation of autophagy and the Hippo signaling pathway emerged as potential underlying mechanisms, findings with potential to inform personalized treatment strategies for patients with acquired chemoresistance.

2024-06-01·Mini reviews in medicinal chemistry

In Silico Pharmacokinetics, Molecular Docking and Molecular Dynamics Simulation Studies of Nucleoside Analogs for Drug Discovery- A Mini Review

Review

作者: Saha, Supriyo ; Ozeki, Yasuhiro ; Munia, Nasrin S ; Kawsar, Sarkar M A

Abstract::

Nucleoside analogs have been widely used as antiviral, antitumor, and antiparasitic agents due to their ability to inhibit nucleic acid synthesis. Adenosine, cytidine, guanosine, thymidine and uridine analogs such as didanosine, vidarabine, remdesivir, gemcitabine, lamivudine, acyclovir, abacavir, zidovusine, stavudine, and idoxuridine showed remarkable anticancer and antiviral activities. In our previously published articles, our main intention was to develop newer generation nucleoside analogs with acylation-induced modification of the hydroxyl group and showcase their biological potencies. In the process of developing nucleoside analogs, in silico studies play an important role and provide a scientific background for biological data. Molecular interactions between drugs and receptors followed by assessment of their stability in physiological environments, help to optimize the drug development process and minimize the burden of unwanted synthesis. Computational approaches, such as DFT, FMO, MEP, ADMET prediction, PASS prediction, POM analysis, molecular docking, and molecular dynamics simulation, are the most popular tools to culminate all preclinical study data and deliver a molecule with maximum bioactivity and minimum toxicity. Although clinical drug trials are crucial for providing dosage recommendations, they can only indirectly provide mechanistic information through researchers for pathological, physiological, and pharmacological determinants. As a result, in silico approaches are increasingly used in drug discovery and development to provide mechanistic information of clinical value. This article portrays the current status of these methods and highlights some remarkable contributions to the development of nucleoside analogs with optimized bioactivity.

1,364

项与吉西他滨相关的新闻（医药）

2024-07-24

·Business Wire

GeneCentric Therapeutics Announces American Medical Association Has Granted a PLA Code for PurIST Pancreatic Cancer Test

DURHAM, N.C.--( BUSINESS WIRE )-- GeneCentric Therapeutics , a company making precision medicine more precise through RNA-based diagnostics, announced today that the American Medical Association (AMA) has granted a PLA code for the PurIST SM pancreatic cancer test. PurIST is commercially available under a collaboration agreement with Tempus AI, Inc. (NASDAQ: TEM) and run on its xR platform. The PurIST PLA code is the first CPT code created to describe an algorithm-only analysis from previously sequenced, LDT, transcriptomic (RNA) data and represents a meaningful step toward reimbursement for AI-enabled algorithms. “ Receipt of a PurIST-specific PLA test code further supports the significance of GeneCentric’s pipeline of next-generation AI-derived tests,” said Michael Milburn, PhD, President and CEO of GeneCentric Therapeutics. “ This is a key step toward reimbursement and successful commercialization for PurIST, and we’re excited about the importance of this test in guiding first-line treatments for pancreatic cancer patients.” Pancreatic cancer has one of the highest mortality rates among all major cancers, and there has been limited availability of validated diagnostic tests or biomarkers to guide first-line treatment selection. The PurIST test classifies the tumors of patients with unresectable stage III or stage IV pancreatic ductal adenocarcinoma (PDAC) as either a basal or classical subtype and can help guide first-line therapy. About the PurIST Test PurIST identifies the molecular subtype of patients with unresectable stage III or stage IV PDAC and classifies patients with PDAC into either a basal or classical subtype and may help inform first-line therapy management. Tempus and GeneCentric recently completed a new clinical validation study demonstrating that PurIST can be used to help predict overall survival of classical patients between standard-of-care first-line therapies, FOLFIRINOX and gemcitabine nab-paclitaxel. The PurIST test is available for ordering as part of the on-line Tempus HUB or via paper requisition forms for orders in the United States. Providers and patients can learn more about the PurIST test on the Tempus website . About Pancreatic Cancer Pancreatic cancer is the 10th most commonly diagnosed cancer in the U.S. and the 12th most common cancer worldwide. The National Cancer Institute estimates there will be over 64,440 new cases and more than 51,750 deaths in the U.S. alone in 2024, making it the third-leading cause of cancer-related deaths in the U.S. with one of the highest mortality rates of all major cancers. More than 90% of pancreatic cancers are pancreatic ductal adenocarcinoma (PDAC), and the 5-year overall survival for resectable/borderline-resectable and non-resectable PDAC is approximately 20% and 1-3%, respectively. The three main treatments for PDAC are surgical resection (if diagnosed early), radiation therapy and chemotherapy. For resectable tumors, surgical resection is provided with curative intent, however, for non-resectable tumors, chemotherapy such as FOLFIRINOX or gemcitabine with nab-paclitaxel is often used. About GeneCentric GeneCentric Therapeutics, Inc., a leader in RNA-based genomic biomarker and next-generation companion diagnostics development, is based in Durham, North Carolina. They have developed a deep pipeline of gene signatures and related diagnostic tests by parsing the complexity of tumor biology using their RNA-based Tumor and Immune Micro-Environment (rT(I)ME) Explorer platform and AI technology to identify responder populations to oncology therapeutics. Using their EXpressCT (Expression Signatures Through Circulating Tumor Signals) platform, these signatures can be applied to liquid biopsy. GeneCentric commercializes its technology through strategic collaborations with biopharmaceutical and diagnostics companies in applications throughout preclinical testing, clinical drug development and commercialization lifecycle phases. For more information, visit www.genecentric.com or follow us on LinkedIn .

临床研究

2024-07-23

·药研发

【药研发0109】元羿引进一款神经系统罕见病新药 | 智翔金泰IL-17单抗新适应症报产...

元羿引进一款神经系统罕见病新药。元羿生物宣布与Praxis Precision公司就后者临床后期高选择性T型钙通道小分子抑制剂ulixacaltamide达成合作许可协议，获得该新药在大中华地区开发和商业化权益，用于治疗原发性震颤。根据协议，Praxis将获得1500万美元的首付款，2.64亿美元的开发、监管和商业化里程碑后期付款，以及产品在大中华地区的销售分成。原发性震颤是一种神经系统疾病。 1.BMS白蛋白紫杉醇中国获批治疗胰腺癌。百时美施贵宝原研产品白蛋白紫杉醇Abraxane（凯素）获国家药监局批准新适应症，联合吉西他滨一线治疗转移性胰腺癌患者。在III期研究MPACT2中，Abraxane联合方案较对照药物可显著延长患者总生存期（中位OS：8.5个月vs6.7个月，P<0.001），降低28%的死亡风险。此前，Abraxane已在中国获批用于治疗联合化疗失败的转移性乳腺癌或辅助化疗后6个月内复发的乳腺癌。 2.罗氏玛巴洛沙韦中国获批治疗儿童流感。罗氏的抗流感药玛巴洛沙韦干混悬剂获国家药监局批准上市，用于儿童单纯性甲型和乙型流感患者。玛巴洛沙韦是一款具有创新作用机制的帽状结构依赖性核酸内切酶抑制剂，也是获批治疗流感的首个单剂量口服药物。此前，NMPA已批准玛巴洛沙韦片在中国上市，用于治疗12周岁及以上急性无并发症的流感患者。 3.智翔金泰IL-17单抗新适应症报产。智翔金泰自研IL-17A单抗赛立奇单抗注射液的新适应症上市申请获NMPA受理，用于治疗放射学阳性中轴型脊柱关节炎。该产品通过抗体特异性结合血清中的IL-17A蛋白，阻断IL-17A与IL-17RA的结合，抑制炎症的发生和发展，对IL-17A过表达的斑块状银屑病、中轴型脊柱关节炎等自身免疫性疾病具有治疗效果。此前，该新药用于治疗斑块状银屑病的NDA已获得NMPA受理。 4.普方FRα靶向ADC获卵巢癌快速通道资格。普方生物靶向FRα的ADC药物rinatabart sesutecan (Rina-S，PRO1184)获FDA授予快速通道资格，用于治疗表达叶酸受体α（FRα）的高级别浆液性或子宫内膜样铂耐药的卵巢癌患者。在治疗局部晚期/转移性实体瘤的Ⅰ/Ⅱ期PRO1184-001临床中，Rina-S在所有FRα表达水平的卵巢癌和子宫内膜癌患者组别中展现出积极的抗肿瘤活性，而且药物耐受性良好。普方生物正在中美两国同步Rina-S的临床开发。 5.艾伯维CD3/BCMA双抗中国报IND。艾伯维1类生物制品ABBV-383输注用溶液的临床试验申请获CDE受理，开发适应症为“多发性骨髓瘤”。ABBV-383（TNB-383B）是TeneoOne公司开发的一款BCMA/CD3双抗，旨在引导自身免疫系统靶向和杀死表达BCMA抗原的肿瘤细胞。该新药目前正在海外开展多发性骨髓瘤的III期临床。此外，该产品还被开发用于治疗AL淀粉样变性。国际药讯 1.Lyndra公司长效口服利培酮Ⅲ期临床成功。Lyndra公司基于其新型口服给药LYNX药物递送平台开发、只需每周一次给药的利培酮（LYN-005），在治疗精神分裂症和分裂情感性障碍成人患者的Ⅲ期临床STARLYNG-1（LYN-005-C-301）研究达到主要和次要终点。药代动力学（PK）特征数据显示，LYN-005（每周口服一次）与速释利培酮（每日服用，Risperdal）的疗效相当；而且LYN-005组受试者在研究期间保持阳性和阴性症状量表（PANSS）的评分稳定。 2.拜耳帕金森病基因疗法早期临床积极。拜耳旗下公司Asklepios BioPharmaceutical（AskBio）基因疗法AB-1005（AAV2-GDNF）治疗帕金森病（PD）的Ⅰb期临床达到主要终点。神经外科医师通过磁共振成像（MRI）监测的对流增强给药方式将AB-1005一次性双侧壳核注射给药，所有患者对AB-1005的神经外科给药方式耐受性良好，目标壳核覆盖率达到63%±2%；而且无严重不良事件发生。后期继续进行给药后5年的临床随访。 3.Claris公司融资开发新型角膜愈合疗法。Claris Bio公司宣布完成5700万美元的A轮融资，以用于推进其基于重组人源肝细胞生长因子（dHGF）变体的眼科溶液oremepermin-α的临床开发，用于治疗神经营养性角膜病变患者。该产品具有促进上皮生长、神经营养、抗炎和抗纤维化的特性，有潜力恢复角膜的结构和功能完整性。oremepermin-α还将开发其他适应症包括角膜缘干细胞缺乏症和原有角膜瘢痕等。 4.罗氏超20亿美元开发精准肿瘤学靶点。罗氏与MOMA Therapeutics达成战略合作和许可协议，将利用后者专有的知识库平台-KnowledgeBase，合作识别和开发创新精准肿瘤学靶点。MOMA的药物发现平台-KnowledgeBase集成了结构功能分析、先导化合物发现技术和计算赋能的先导化合物优化。根据协议，MOMA将获得6600万美元的预付款，项目交易总金额合计高达20亿美元。 5.诺和诺德拟开发肥胖和MASH新药。诺和诺德分别与Flagship Pioneering孵化的Omega公司和Cellarity公司达成新药研究合作，开发用于肥胖管理的表观遗传药物和针对代谢相关脂肪性肝炎（MASH）的小分子新药。Omega专有技术平台可合理设计和制造可编程的mRNA编码表观遗传药物，旨在精确调节IGD以恢复单基因或多基因的表达功能。根据协议，两家公司将获得研发费用，还有资格获得高达5.32亿美元的首付款和里程碑付款，以及分层版税。 6.张锋联合创建公司获5700万美元融资。Moonwalk Biosciences公司宣布完成5700万美元的种子和A轮融资，以用于支持其表观遗传分析和工程技术平台的持续开发，并将其表观遗传治疗药物管线向临床推进。该公司的科学联合创始人为Broad研究所的著名学者张锋博士。Moonwalk的创新表观遗传编辑器旨在利用细胞的自然调节系统一步准确、永久地控制多个基因，以避免现有的基因编辑方法改变DNA序列带来的潜在风险。医药热点 1. 江苏新发现1例小p血型。近日，江苏省泰兴市人民医院输血科发现一例小p血型。我国一般把表型频率低于千分之一的血型称为“稀有血型”。据资料记载，在中国人群中Rh阴性血“熊猫血”约有0.4%，而小p血型出现频率低于百万分之一。目前，我国记录在案的小p血型仅有9人，相当罕见。 2.美国南加州大学开发出人脑类器官。美国加州大学Keck医学院Giorgia Quadrato团队开发一种人类小脑类器官（hCerO），可以让包含浦肯野细胞在内的功能性小脑细胞，在体外人源三维环境中长期健康存活和成熟。这也是首次在全人源系统中成功培育出功能神经元分子和电生理特征的浦肯野细胞。相关成果于2024年1月4日发表在Cell Stem Cell杂志上。 3.抖音正式发文，开放处方药经营。1月4日深夜，抖音电商公开上线两则处方药相关公告，分别为【处方药品类管理规范】和【处方药准入品牌清单】。经查询，在商家申请入驻时，已可在药品类目下选择到非处方药和处方药的选项，但目前两者分别限为定向招商和定向邀约，均未全面放开。同时，【处方药准入品牌清单】已公示首批500个准入品牌清单。其中涉及AstraZeneca/阿斯利康、白云山、辉瑞、同仁堂、SUNFLOWER/葵花药业等知名企业。评审动态 1. CDE新药受理情况（01月08日) 2. FDA新药获批情况（北美01月05日）股市资讯上个交易日 A 股医药板块 -1.75%涨幅前三跌幅前三莎普爱思+9.98% 峆一药业-8.62%万泰生物+8.28% 星昊医药-8.17%生物谷 +7.69% 新赣江 -7.83% 【贝达药业】1、收到国家药品监督管理局签发的《受理通知书》，BPI-520105片药品临床试验申请获得受理。2、收到国家药品监督管理局签发的《受理通知书》，BPI-221351片药品临床试验申请获得受理。【恒瑞医药】子公司上海盛迪医药有限公司和苏州盛迪亚生物医药有限公司收到国家药品监督管理局核准签发的阿得贝利单抗注射液、注射用SHR-A1921和SHR-8068注射液的《药物临床试验批准通知书》。【艾力斯】上海艾力斯医药科技股份有限公司宣布其核心产品甲磺酸伏美替尼片被国家药品监督管理局药品审评中心纳入拟突破性治疗品种公示名单。- The End -戳“阅读原文”，了解更多医药研发及股市资讯。

快速通道引进/卖出抗体药物偶联物上市批准临床申请

2024-07-19

·PipelineReview

Bristol Myers Squibb Receives European Medicines Agency Validation of Application for Opdivo (nivolumab) plus Yervoy (ipilimumab) for First-Line Treatment of Unresectable or Advanced Hepatocellular Carcinoma

The Application is based on Phase 3 CheckMate – 9DW trial results demonstrating improved survival with Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib in this patient population PRINCETON, NJ, USA I July 19, 2024 I Bristol Myers Squibb (NYSE: BMY) today announced that the European Medicines Agency (EMA) validated its Type II variation application for Opdivo ® (nivolumab) plus Yervoy ® (ipilimumab) as a potential first-line treatment option for adult patients with unresectable or advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy. The application was based on results from the Phase 3 CheckMate -9DW trial and validation of the application confirms the submission is complete and begins the EMA’s centralized procedure review. “Approximately 62,000 cases of liver cancer are diagnosed annually in the European Union, with HCC being the predominant type. Despite recent treatment advances, the prognosis remains poor for patients in more advanced stages which highlights the need for therapies with better clinical outcomes,” said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. “ We look forward to working with the EMA to advance our application for Opdivo plus Yervoy to provide a new first-line dual immunotherapy combination treatment optionfor adult patients with unresectable or advanced hepatocellular carcinoma in the European Union.” In the Phase 3 CheckMate -9DW trial, Opdivo plus Yervoy demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) compared to investigator’s choice of lenvatinib or sorafenib, which showed the clinical benefit of the combination treatment option when provided in the first-line setting. The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified. Results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting . Bristol Myers Squibb thanks the patients and investigators involved with the Phase 3 CheckMate -9DW clinical trial. About CheckMate -9DW CheckMate -9DW is a Phase 3 randomized, open-label trial evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib monotherapy in patients with unresectable or advanced hepatocellular carcinoma who have not received prior systemic therapy. Approximately 668 patients were randomized to receive Opdivo plus Yervoy ( Opdivo 1mg/kg plus Yervoy 3 mg/kg Q3W for up to four doses, followed by Opdivo monotherapy 480 mg for a maximum duration of 2 years) infusion, or single agent lenvatinib or sorafenib as oral capsules in the control arm. The primary endpoint of the trial is overall survival and key secondary endpoints include objective response rate and time to symptom deterioration. About Hepatocellular Carcinoma Liver cancer is the third most frequent cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for 75% – 85% of all liver cancers. HCC is often diagnosed in an advanced stage, where effective treatment options are limited and are usually associated with poor outcomes. Up to 70% of patients experience recurrence within five years, particularly those still considered to be at high risk after surgery or ablation. While most cases of HCC are caused by hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, metabolic syndrome and nonalcoholic steatohepatitis (NASH) are rising in prevalence and expected to contribute to increased rates of HCC. Bristol Myers Squibb: Creating a Better Future for People with Cancer Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research programs uniquely position the company to approach cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future. About Opdivo Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers. Opdivo ’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression. In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union. About Yervoy Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types. INDICATIONS OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma. OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC). OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM). OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC). OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC. OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma. OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy. OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT). OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC). OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC). OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. Please see US Full Prescribing Information for OPDIVO and YERVOY . Clinical Trials and Patient Populations Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238– adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K–adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648–previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 648–previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma. About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn , Twitter , YouTube , Facebook and Instagram . SOURCE: Bristol Myers Squibb

临床结果临床3期免疫疗法上市批准引进/卖出

100 项与吉西他滨相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D02368	-	-	DB00441

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适应症	最高研发状态	国家/地区	公司	日期
胰腺癌	临床3期	-	RenovoRx, Inc.	2023-06-01
转移性胰腺导管腺癌	临床3期	澳大利亚	Panbela Therapeutics, Inc.	2022-08-04
局部晚期胰腺腺癌	临床3期	美国	RenovoRx, Inc.	2018-03-12
局部晚期胰腺腺癌	临床3期	比利时	RenovoRx, Inc.	2018-03-12
胆道肿瘤	临床2期	美国	Merck Sharp & Dohme LLC	2024-07-08
晚期恶性实体瘤	临床2期	美国	FUJIFILM Pharmaceuticals USA, Inc.	2022-06-01
晚期尿路上皮癌	临床2期	美国	FUJIFILM Pharmaceuticals USA, Inc.	2022-06-01
局部晚期非小细胞肺癌	临床2期	美国	FUJIFILM Pharmaceuticals USA, Inc.	2022-06-01
非小细胞肺癌	临床2期	美国	Merck & Co., Inc.	2022-01-30
尿路上皮癌	临床2期	美国	Merck & Co., Inc.	2022-01-30

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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


NCT01625260 (CTgov)	临床1/2期	非肌层浸润性膀胱肿瘤	12	Gemcitabine+ALT-801 (0.06 mg/kg ALT-801 With 1000 mg/m^2 Gemcitabine)	選蓋鹽鑰築衊廠製選醖(鏇鑰艱範遞襯壓夢網蓋) = 鏇獵鏇壓窪網繭範選構廠醖蓋艱淵構觸蓋鏇範 (衊鬱鹽壓餘觸積蓋鏇膚, 獵顧糧顧壓糧餘膚範積 ~ 衊蓋廠繭願蓋蓋膚簾鏇) 更多	-	2024-07-19
NCT01625260 (CTgov)	临床1/2期	非肌层浸润性膀胱肿瘤	12	Gemcitabine+ALT-801 (0.08 mg/kg ALT-801 With 1000 mg/m^2 Gemcitabine)	選蓋鹽鑰築衊廠製選醖(鏇鑰艱範遞襯壓夢網蓋) = 窪膚憲憲顧醖艱膚膚簾廠醖蓋艱淵構觸蓋鏇範 (衊鬱鹽壓餘觸積蓋鏇膚, 糧範艱網鑰醖窪廠壓餘 ~ 網顧觸餘築觸鬱願糧網) 更多	-	2024-07-19
NCT02827201 (PRODIGE 37-FIRGEMAX, CTgov)	临床2期	胰腺继发性恶性肿瘤	127	FOLFIRI.3+nab-paclitaxel+gemcitabine (Nab-paclitaxel + Gemcitabine/FOLFIRI.3)	顧構築廠鏇壓顧範窪廠(糧窪範蓋顧衊顧齋鬱願) = 鏇鑰網選襯鬱膚積築顧餘壓齋構醖襯襯鏇觸襯 (網鏇簾醖醖積鏇襯窪網, 廠廠鬱醖鹽構淵蓋築觸 ~ 餘鏇鹹鬱齋鹽鏇簾願繭) 更多	-	2024-07-09
NCT02827201 (PRODIGE 37-FIRGEMAX, CTgov)	临床2期	胰腺继发性恶性肿瘤	127	nab-paclitaxel+gemcitabine (Nab-paclitaxel + Gemcitabine)	顧構築廠鏇壓顧範窪廠(糧窪範蓋顧衊顧齋鬱願) = 製襯簾衊觸憲簾遞築齋餘壓齋構醖襯襯鏇觸襯 (網鏇簾醖醖積鏇襯窪網, 獵鏇鏇壓選鏇積繭廠顧 ~ 襯鬱憲願願觸糧獵鬱製) 更多	-	2024-07-09
NCT03044587 (NIFE-AIO-YMO HEP-0315, Pubmed)	临床2期	晚期胆道癌一线	91	Nanoliposomal irinotecan/fluorouracil/leucovorin (nal-IRI/FU/LV)	積膚製範醖衊選觸艱築(選窪鬱鏇齋鬱夢獵憲鹽) = 範鹽廠繭積廠繭膚糧積蓋積齋鹽範齋範齋糧鏇 (鏇艱鏇膚鹹遞壓廠鑰膚, 2.4 ~ 9.6) 更多	积极	2024-06-06
NCT03044587 (NIFE-AIO-YMO HEP-0315, Pubmed)	临床2期	晚期胆道癌一线	91	Gemcitabine/cisplatin (G/C)	積膚製範醖衊選觸艱築(選窪鬱鏇齋鬱夢獵憲鹽) = 築觸範繭獵築範餘範鹹蓋積齋鹽範齋範齋糧鏇 (鏇艱鏇膚鹹遞壓廠鑰膚, 2.5 ~ 7.9) 更多	积极	2024-06-06
NCT05669482 (RAMP 205, ASCO2024) 人工标引	临床1/2期	转移性胰腺导管腺癌一线	18	Avutometinib/defactinib + gemcitabine/nab-paclitaxel	窪壓鏇襯觸淵鑰簾艱繭(艱簾鹹網醖憲壓膚繭窪) = 窪構夢蓋獵衊襯願獵顧顧齋積獵糧顧簾積築蓋 (簾蓋襯鑰積選憲築艱憲 ) 更多	积极	2024-05-24
NCT05318573 (ASCO2024) 人工标引	临床2期	晚期恶性实体瘤 PD-L1 expression \| mutational burden	12	FF-10832+PEM	餘夢鑰選築壓鑰鏇製製(蓋構願鹹壓憲廠夢鬱選) = Common AEs related to FF832 were Gr≤2 fatigue (50%) with 1 Gr 3, anemia (33%) with 2 Gr 3, & Gr ≤2 decreased appetite, diarrhea, ↑AST, ↑AlkPhos, muscular weakness, nausea, and pyrexia (25% each). Common AEs related to FF832+PEM were Gr≤2 fatigue (33%) & nausea (25%). Three pts had Gr≤2 infusion reactions with the first FF832 infusion; FF832 dose was reduced to 30 mg/m2 after Cycle 1 in 3 pts due to Gr 3 rash (1), Gr 2 fatigue (1). 獵製憲獵鑰廠餘鑰鹹艱 (壓願獵齋窪鹹網鏇齋廠 )	积极	2024-05-24
NCT04203160 (BilT-04, ASCO2024) 人工标引	临床1/2期	晚期胆管癌一线	75	Gemcitabine and Cisplatin + Devimistat	夢夢艱鹹齋遞廠醖衊艱(製餘鹽範選鏇淵遞憲鏇) = 壓遞鏇積蓋壓築衊夢鹹獵膚獵齋窪簾廠網襯獵 (艱鹽顧鏇鏇襯簾選餘艱, 17.9 ~ 44.6) 更多	不佳	2024-05-24
NCT04203160 (BilT-04, ASCO2024) 人工标引	临床1/2期	晚期胆管癌一线	75	Gemcitabine and Cisplatin	夢夢艱鹹齋遞廠醖衊艱(製餘鹽範選鏇淵遞憲鏇) = 淵淵獵網鹽蓋積鏇鏇膚獵膚獵齋窪簾廠網襯獵 (艱鹽顧鏇鏇襯簾選餘艱, 19.2 ~ 74.9) 更多	不佳	2024-05-24
ASCO2024	N/A	原发性腹膜癌 \| 卵巢癌 \| 输卵管癌	-	Gemcitabine plus cisplatin	淵廠壓蓋艱範願膚獵蓋(願繭製築窪鬱鬱鑰鹽夢) = 獵顧蓋選網網選鹹簾繭糧積製遞簾願膚夢糧選 (餘襯構襯選簾鹽淵選齋, 36.6 ~ 51.9) 更多	积极	2024-05-24
MDACC (ASCO2024)	临床2期	尿路上皮癌	76	Gemcitabine	顧築觸範鹽淵繭鏇簾顧(夢鬱構範鑰壓遞襯廠願) = required in 15 (19.7%) 鏇蓋憲襯簾憲獵顧積積 (廠壓觸鹽襯鏇觸窪構繭 ) 更多	不佳	2024-05-24
NCT03793088 (ASCO2024)	N/A	纤维板层肝细胞癌新辅助	67	Lenvatinib, gemcitabine, and oxaliplatin (GOL)	窪繭鹹顧觸選鏇築廠襯(糧選壓淵襯製鏇蓋積繭) = 鹽窪窪製觸鹹顧積窪齋淵觸淵夢鬱廠遞積壓蓋 (築顧淵選選鑰壓顧淵遞 ) 更多	积极	2024-05-24
MP16-14 (AUA2024)	临床2期	非肌层浸润性膀胱尿路上皮癌	25	Intravesical Gemcitabine and Docetaxel	艱壓膚簾遞鹹夢積鏇膚(窪淵餘糧觸壓製網範築) = 蓋鹽積簾鹹蓋築鏇鹽鹽鹽艱獵齋壓壓觸齋鏇襯 (製製築願獵艱獵餘遞蓋 ) 更多	积极	2024-05-01