A Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD1390 (NSC# 852149) When Combined With Focal Radiation in Pediatric Patients With High Grade Glioma

This phase I clinical trial studies the side effects and best dose of AZD1390 and to see how well it works when given together with radiation therapy for the treatment of pediatric patients with high grade glioma, diffuse midline glioma or diffuse intrinsic pontine glioma. AZD1390 is in a class of medications called kinase inhibitors. It works by blocking the signals that cause cancer cells to multiply. This helps to stop the spread of cancer cells. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving AZD1390 with radiation may be safe, tolerable, and/or effective in treating pediatric patients with high grade glioma, diffuse midline glioma or diffuse intrinsic pontine glioma.

开始日期2025-05-07

申办/合作机构

The Children's Oncology Group Foundation, Inc.

NCT05678010

/ Active, not recruiting临床1期IIT

A Phase I Study Assessing the Safety and Tolerability of Ascending Doses of AZD1390 in Combination with Stereotactic Body Radiation Therapy (SBRT) in Patients with Metastatic Solid Tumor Malignancies

The purpose of this study is to find out whether AZD1390 combined with stereotactic body radiation therapy/SBRT is a safe treatment for people with metastatic solid tumor cancer

开始日期2023-05-17

申办/合作机构

Memorial Sloan Kettering Cancer Center

[+1]

NCT05116254

/ Recruiting临床1期IIT

Sarcomas and DDR-Inhibition; a Neoadjuvant Phase I Combined Modality Study.

To assess the safety and tolerability profile, in the pre- and perioperative period (up to 30 days post-surgery), of combined modality treatment (CMT) by administering AZD1390 with or without durvalumab and RT concurrently treating newly diagnosed, non-metastatic soft tissue sarcoma patients with DDRi-based CMT, in the specific context of systemic toxicities, wound healing post-surgery and in defining the RP2D for the combinations to support further clinical evaluation.

开始日期2022-07-18

申办/合作机构

Netherlands Cancer Insitute

[+2]

100 项与 AZD-1390 相关的临床结果

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100 项与 AZD-1390 相关的转化医学

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100 项与 AZD-1390 相关的专利（医药）

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项与 AZD-1390 相关的文献（医药）

2025-03-01·Molecular biotechnology

Computational Analysis of Non-synonymous SNPs in ATM Kinase: Structural Insights, Functional Implications, and Inhibitor Discovery

Article

作者: Prince, Sabina Evan ; Sengupta, Tiasa ; Samdani, Poorva ; Panchal, Nagesh Kishan

Ataxia telangiectasia-mutated (ATM) protein kinase, a key player in cellular integrity regulation, is known for its role in DNA damage response. This study investigates the broader impact of ATM on cellular processes and potential clinical manifestations arising from mutations, aiming to expand our understanding of ATM's diverse functions beyond conventional roles. The research employs a comprehensive set of computational techniques for a thorough analysis of ATM mutations. The mutation data are curated from dbSNP and HuVarBase databases. A meticulous assessment is conducted, considering factors such as deleterious effects, protein stability, oncogenic potential, and biophysical characteristics of the identified mutations. Conservation analysis, utilizing diverse computational tools, provides insights into the evolutionary significance of these mutations. Molecular docking and dynamic simulation analyses are carried out for selected mutations, investigating their interactions with Y2080D, AZD0156, and quercetin inhibitors to gauge potential therapeutic implications. Among the 419 mutations scrutinized, five (V1913C, Y2080D, L2656P, C2770G, and C2930G) are identified as both disease causing and protein destabilizing. The study reveals the oncogenic potential of these mutations, supported by findings from the COSMIC database. Notably, Y2080D is associated with haematopoietic and lymphoid cancers, while C2770G shows a correlation with squamous cell carcinomas. Molecular docking and dynamic simulation analyses highlight strong binding affinities of quercetin for Y2080D and AZD0156 for C2770G, suggesting potential therapeutic options. In summary, this computational analysis provides a comprehensive understanding of ATM mutations, revealing their potential implications in cellular integrity and cancer development. The study underscores the significance of Y2080D and C2770G mutations, offering valuable insights for future precision medicine targeting-specific ATM. Despite informative computational analyses, a significant research gap exists, necessitating essential in vitro and in vivo studies to validate the predicted effects of ATM mutations on protein structure and function.

2025-01-01·EXPERIMENTAL CELL RESEARCH

AZD1390, an Ataxia telangiectasia mutated inhibitor, enhances cisplatin mediated apoptosis in breast cancer cells

Article

作者: Ağca, Can Ali ; Özdemir, Deniz

Genomic instability is often caused by deficiencies in DNA damage repair pathways, making therapeutic targeting of DDR beneficial for cancer patients with specific DDR functions. ATM kinase plays a critical role in various cellular processes and its deficiency increases sensitivity to DDR-targeted agents in different cancers. Recent studies highlight ATM inhibition as a potential clinical target, with AZD1390 being a notable ATM inhibitor due to its potent and selective inhibition, ability to accumulate at DNA breaks. The study aimed to evaluate the potential anti-cancer effects of AZD1390, a key component of the DNA damage response, in breast cancer cells. The impact of the combination of AZD1390 and cisplatin on various parameters such as cell viability, proliferation, colony formation capacity, DNA damage, reactive oxygen species (ROS) levels, mitochondrial membrane potential, cell cycle progression, and cell death in breast cancer cells was evaluated using several methodologies, including WST-1 assays, real-time cell analysis, colony formation assays, comet assays, DCF-DA, MMP/JC-1 staining assays, flow cytometry along with Western blot analysis. We found that AZD1390 and cisplatin displayed synergistic antitumor effects in breast cancer cells at low doses. Addinationaly exhibited significant anti-proliferative effects in colony formation and real-time cell proliferation experiments, increasing intracellular ROS levels and mitochondrial membrane potential.The combined treatment also arrested the cell cycle at the G2-M point. Furthermore, combination of AZD1390 with cisplatin enhances its apoptotic effects in MCF-7 and MDA-MB-231 cells. These findings could aid in developing new treatments for breast cancer that exploit the genomic instability of cancer cells.

2024-09-12·JOURNAL OF MEDICINAL CHEMISTRY

Small Molecular Inhibitors That Target ATM for Drug Discovery: Current Research and Potential Prospective

Review

作者: Li, Xiaoxue ; Wang, Yuxi ; Zhang, Jifa ; Qian, Chunlin

The protein kinase ataxia telangiectasia mutated (ATM) is a constituent of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, exerting a pivotal influence on diverse cellular processes, notably the signaling of double-strand DNA breaks (DSB) and stress response. The dysregulation of ATM is implicated in the pathogenesis of cancer and other diseases such as neurodegeneration. Hence, ATM is deemed a promising candidate for potential therapeutic interventions across a spectrum of diseases. Presently, while ATM small molecule inhibitors are not commercially available, various selective inhibitors have progressed to the clinical research phase. Specifically, AZD1390, WSD0628, SYH2051, and ZN-B-2262 are under investigation in clinical studies pertaining to glioblastoma multiforme and advanced solid tumors, respectively. In this Perspective, we encapsulate the structure, biological functions, and disease relevance of ATM. Subsequently, we concentrate on the design concepts and structure-activity relationships (SAR) of ATM inhibitors, delineating potential avenues for the development of more efficacious ATM-targeted inhibitors.

项与 AZD-1390 相关的新闻（医药）

2025-05-13

·PRNewswire

Global Coalition for Adaptive Research Announces Initiation of AZD1390 in GBM AGILE Trial

AstraZeneca's AZD1390 Now Enrolling in GBM AGILE, a Registrational-Intent Phase 2/3 Adaptive Platform Trial for Patients with Glioblastoma AZD1390 Arm Will Recruit Patients with Newly Diagnosed Glioblastoma Across Multiple International Trial Sites LARKSPUR, Calif., May 13, 2025 /PRNewswire/ -- The Global Coalition for Adaptive Research (GCAR) today announced the activation of AstraZeneca's AZD1390 in GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment – NCT03970447), the world's first global adaptive platform trial for glioblastoma. The AZD1390 arm will be evaluated for the treatment of adult patients with newly diagnosed glioblastoma. Glioblastoma is the most aggressive and common form of primary brain cancer. Treatment options and patient outcomes have seen little progress over the past several decades. Continue Reading GBM AGILE Adaptive Global Innovative Learning Environment AstraZeneca's AZD1390 is entering the GBM AGILE trial as the 7th investigational arm. Since launching in 2019, the GBM AGILE trial has evaluated multiple therapies and has screened over 2,300 patients at trial locations in six countries. GBM AGILE, a seamless phase 2/3 trial, is conducted under a master protocol, allowing multiple therapies or combinations of therapies from different pharmaceutical companies to be evaluated simultaneously against a common control arm. With its innovative design and efficient operational infrastructure, data from GBM AGILE can potentially be used as the foundation for a new drug application (NDA) and registrations to the US FDA and other health authorities. Professor Anthony Chalmers, Chair of Clinical Oncology at the University of Glasgow and Dr. Patrick Wen, Director, Center for Neuro-Oncology at Dana-Farber Cancer Institute, and Professor of Neurology at Harvard Medical School, are serving as arm Principal Investigators for AZD1390's evaluation in GBM AGILE. Dr. Timothy Cloughesy, Director, Neuro-Oncology Program and Distinguished Professor of Neurology at the University of California, Los Angeles, is the Global Principal Investigator for the overall study. "Glioblastoma is an invariably fatal cancer with few effective treatment options. There is an urgent need for better treatment options," said Professor Anthony Chalmers. "We are excited to evaluate AZD1390 in GBM AGILE based on encouraging data from previous studies and the extensive evidence that AZD1390 can increase the effectiveness of radiation therapy. This investigational drug has clear potential to improve outcomes for glioblastoma patients." "GBM AGILE is designed to rapidly identify and confirm effective therapies for patients with glioblastoma through response adaptive randomization," said Dr. Patrick Wen. "With the addition of AZD1390 to GBM AGILE, a global clinical trial, we are able to offer GBM patients access to the latest and most promising investigational therapies." AZD1390 is a brain penetrant ataxia telangiectasia mutant (ATM) kinase inhibitor that blocks ATM-dependent signaling and repair of DNA double strand breaks (DSBs) in the genome. Preclinically, AZD1390 exhibits activity in combination with agents such as radiation therapy that induce DSBs. AZD1390 has also been shown to achieve clinically relevant concentrations in resected glioblastoma tissue and suppress the ability of tumor cells to repair the DNA damage that is induced by radiation. Furthermore, data from a Phase I trial of AZD1390 with radiotherapy showed a manageable toxicity profile and preliminary efficacy for patients with recurrent glioblastoma and was shared in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024. "At GCAR, we're dedicated to accelerating the development of critically needed therapies for patients facing rare and deadly diseases like glioblastoma," said Dr. Meredith Buxton, CEO and President of GCAR. "We believe master protocols and adaptive platform trials are a powerful way to expedite that progress. We're excited to collaborate with AstraZeneca and look forward to rapidly advancing the development of AZD1390 in GBM AGILE to help address the urgent need for more effective glioblastoma therapies." About Global Coalition for Adaptive Research (GCAR) Global Coalition for Adaptive Research (GCAR) is a 501(c)(3) non-profit corporation uniting physicians, clinical researchers, advocacy and philanthropic organizations, biotech/pharma companies, health authorities, and other key stakeholders in healthcare to expedite the discovery and development of treatments for patients with rare and deadly diseases. As the sponsor of innovative trials, including master protocols and adaptive platform trials, GCAR is dedicated to the advancement of science by modernizing clinical trials that support more efficient, less costly drug development. To learn more about GCAR and its initiatives, visit gcaresearch.org and follow us on social media @GCAResearch. SOURCE Global Coalition for Adaptive Research 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

2025-01-21

·小药说药

合成致死癌症治疗策略的研发进展

关注小药说药，一起成长！前言合成致死性是一种遗传现象，即单个基因缺陷与细胞存活相容，但两个基因的同时缺陷导致细胞死亡或细胞适应性受损。合成致死性提供了一个独特的机会，可以间接靶向以前被认为“难以成药”的蛋白质，包括携带功能丧失（LOF）突变的关键肿瘤抑制蛋白和由扩增或其他基因组改变引起的过表达致癌蛋白。这些与环境相关的相互作用是癌细胞固有和特异性的，因此提供了选择性靶向这些细胞的机会，同时保留了缺乏相关基因组背景的非癌细胞。目前，PARP抑制剂已经在BRCA突变癌症患者中获得临床成功。在此推动下，针对DNA损伤反应途径中多种合成致死相互作用的新型药物正在临床开发中，针对跨越表观遗传、代谢和增殖途径改变的合成致死相互作用的合理策略也已出现，并进入临床前和早期临床试验阶段。靶向合成致死相互作用 DNA损伤反应（DDR）网络可以保持基因组稳定性，抑制复制应激，保护受损的复制叉，并确保高保真DNA复制。DDR成分的遗传性和获得性细胞缺陷与基因组不稳定性的积累有关，导致肿瘤发生和癌症进展。同时，具有这些缺陷的细胞变得依赖于补偿DDR途径生存，从而为合成致命靶向创造了机会。 DNA损伤信号：靶向ATR、ATM和DNA-PK ATR、ATM和CHK1激酶的抑制剂主要通过抑制必需的细胞周期检查点来利用细胞复制应激，导致过早进入有丝分裂和细胞死亡。ATR是一种丝氨酸/苏氨酸蛋白激酶，属于磷脂酰肌醇3-激酶相关激酶（PIKK）家族。当DNA发生损伤时，ATR被激活，并通过下游信号通路参与DNA损伤的检测、复制叉的稳定和损伤修复；激酶ATM通过调节DDR内下游激酶的活性和控制细胞周期检查点进程，在DNA双链断裂（DSB）的修复中起着关键作用；DNA-PK是另一种磷脂酰肌醇3-激酶相关激酶（PIKK），在DNA损伤部位充当邻近修复蛋白的蛋白质支架，在非同源末端连接（NHEJ）中起着关键作用。许多肿瘤细胞由于DNA修复通路的缺陷，高度依赖这些激酶途径来维持其生存和增殖。因此，ATR、ATM和DNA-PK抑制剂与这些缺陷相结合，可导致肿瘤细胞发生合成致死。多种ATR抑制剂已处于临床开发中，包括berzosertib、ceralasterib、elimusertib、camonsertib、tuvusertib、ART0380、ATRN-119、ATG-018和IMP9064等；正在临床试验中测试的ATM抑制剂包括AZD1390和双重ATM和DNA-PK抑制剂XRD-0394和M4076，临床开发中的DNA-PK抑制剂包括AZD7648和peposertib。 DNA复制和细胞分裂：WEE1、PKMYT1、CDC7和PLK4 Wee样激酶1（WEE1）通过催化CDK1和CDK2在Tyr15位置的抑制性磷酸化来调节细胞周期通过G2/M和S检查点的进程。WEE1的抑制在G1/S失调的情况下是合成致死的，例如由CCNE1扩增或TP53突变引起的G1/S失调。正在临床试验中测试的WEE1抑制剂包括adavosertib、azenosertib、Debio 0123、IMP7068、SY-4835、SC0191和ATRN-W1051。蛋白激酶，膜相关酪氨酸-苏氨酸1（PKMYT1）是一种细胞膜相关丝氨酸-苏氨酸蛋白激酶，也调节CDK1和G2/M检查点。功能基因组筛选的数据表明，PKMYT1失活与CCNE1扩增具有合成致死性。此外，除了CCNE1扩增，编码E3泛素连接酶FBXW7基因中的LOF突变和编码PP2A磷酸酶亚基PPP2R1A的基因也可通过PKMYT1抑制靶向。细胞分裂周期7（CDC7）激酶在触发复制起点激活中起着重要作用。携带功能获得TP53突变的细胞依赖于CDC7依赖性DNA复制，这是由于与致癌转录因子MYB合作促进癌症细胞中的CDC7激活。在携带TP53突变的癌症细胞中，CDC7的药理学抑制诱导选择性衰老，而mTOR信号与CDC7联合抑制在促进凋亡细胞死亡方面非常有效。然而，尽管具有明显的临床前活性，但几种CDC7抑制剂（BMS-863233、TAK-931、NMS-1116354和LY3143921）在早期试验中未能显示出足够的疗效。 Polo 样激酶4（PLK4）是一种调节中心粒生物发生的激酶，中心粒是有丝分裂纺锤体组装和染色体分离所需的中心体的重要组成部分。中心粒周围的蛋白质是另一个关键的中心体成分，受E3泛素连接酶TRIM37的负调控。TRIM37的扩增（通常在神经母细胞瘤和乳腺癌中观察到）导致中心体物质耗竭，从而增加了对中心粒进行有丝分裂纺锤体组装的依赖，并使PLK4抑制在这种情况下成为一种有吸引力的治疗策略。目前，两种PLK4抑制剂CFI-400945和RP-1664正在临床试验中进行测试。 DNA修复：WRN、POLQ和USP1 POLQ和泛素特异性蛋白酶1（USP1）是携带BRCA1/2缺陷的癌症中临床相关的合成致死靶点。POLQ是一种广泛保守的DNA聚合酶，也是DSB修复过程中易出错的MMEJ途径的核心介体。来自几项试验的数据表明，POLQ抑制和BRCA1/2缺乏之间存在合成致死关系，这归因于癌症HRR缺陷（HRD）细胞对MMEJ DNA修复的高度依赖性。测试各种POLQ抑制剂的早期试验正在进行中，包括ART4215、novobiocin、ART6043和GSK4524101，作为单一疗法或与各种PARP抑制剂联合使用。 USP1是一种去泛素酶，调节关键的范可尼贫血复合物和跨损伤合成底物，同时抑制NHEJ。在BRCA1缺陷细胞中，USP1在复制叉处特别活跃，其与叉DNA结合并被其激活，同时介导叉保护；抑制USP1会导致复制叉失稳、叉保护失败和细胞死亡。KSQ-4279是一种USP1抑制剂，目前正在I期试验中作为单一疗法或与PARP抑制剂或铂类化疗联合使用进行测试。 Werner综合征ATP-依赖性解旋酶（WRN）功能的丧失与癌细胞中的微卫星不稳定性-高（MSI-H）表型具有合成致死关系。WRN敲除已被证明会在MSI-H细胞中诱导广泛的DSBs、细胞周期失调、基因组不稳定和凋亡，但在体外微卫星稳定细胞中不会诱导。WRN抑制剂HRO761和RO7589831均已进入I期临床试验。靶向合成致死代谢依赖性代谢重编程是癌症的标志，肿瘤代谢的遗传或表观遗传改变，是调节细胞内自由基积累和维持肿瘤进展所需的生物合成和能量需求增加所必需的。甲硫基腺苷磷酸化酶（MTAP）缺失与PRMT5-MAT2A-RIOK1轴成分耗竭之间具有合成致死关系。MTAP的损失导致5′-甲硫腺苷（MTA）的积累，MTA本身通过竞争PRMT5 S-腺苷甲硫氨酸（SAM）结合袋，成为PRMT5的强效和选择性内源性抑制剂。因此，缺乏MTAP功能的细胞PRMT5甲基化水平降低，对进一步的PRMT5耗竭敏感，导致细胞生长抑制。目前正在临床试验中测试几种MTA协同PRMT5抑制剂，如AMG193、MRTX1719和TNG908，以及MAT2A抑制剂IDE397。涉及代谢途径的合成致死相互作用还包括氨基酸和核酸代谢途径中的合成剂量致死性关系。例如，FLT3内部串联重复（FLT3-ITDs）是驱动因素，通过激活参与从头丝氨酸生物合成基因的转录因子4（ATF4）依赖性转录调控，赋予丝氨酸生物合成独特的代谢依赖性。在这种情况下，抑制丝氨酸生物合成中第一个也是唯一的限速酶磷酸甘油酸脱氢酶（PHGDH），使用PHGDH抑制剂WQ-2101在FLT3野生型细胞中亚致死的剂量，会导致凋亡诱导。与FLT3野生型细胞系相比，对携带FLT3-ITD突变的细胞系具有显著的抗增殖作用。靶向表观遗传调控的合成致死策略染色质调节过程的动态控制对细胞功能至关重要。在多达50%的癌症中检测到与读取、添加或删除表观遗传修饰以及影响染色质调节和组织有关的基因突变。SWI/SNF染色质重塑复合物（CRC）是四个ATP依赖性CRC家族之一，能够通过驱逐、动员或沉积核小体来改变染色质结构。编码SWI/SNF成分的基因突变大多导致功能丧失，在所有人类癌症中发生率高达20%。功能基因组筛查已证明SWI/SNF同源对SMARCA4-SMARCA2、ARID1A-ARID1B、SMARCA4-AMARCB1、SMARCA4-ARID2、SMARCA-4-ACTB和SMARCC1-SMARCC2之间存在合成致死相互作用。作为表观遗传合成剂量致死性的另一个例子，研究发现SWI/SNF-BRG1-SMARCA4复合物在弥漫性中线胶质瘤患者中与H3K27M突变的表观遗传依赖性。SMARCA4与SOX10在H3K27M突变胶质瘤细胞的调节元件上共定位，以调节参与细胞增殖和细胞外基质的基因表达。H3K27M的功能缺失导致SMARCA4染色质在SOX10和H3K27乙酰化标记的增强子上的结合减少。使用靶向蛋白降解剂或小分子抑制剂靶向SMARCA4，在体外和体内模型中产生了抗肿瘤活性。小结合成致死作为一种新兴的肿瘤治疗策略，近年来备受关注。它基于两个非致死性基因同时受到抑制或干扰时，会导致细胞死亡的现象。合成致死的发现为癌症治疗提供了新的思路，推动了相关药物的开发。在合成致死策略中，PARP抑制剂是最成功的案例之一，PARP抑制剂通过抑制PARP的活性，导致DNA损伤无法修复，从而引起肿瘤细胞死亡。目前，PARP抑制剂已被批准用于治疗携带BRCA1或BRCA2基因突变的乳腺癌和卵巢癌。除了PARP抑制剂，研究人员还在积极探索其他合成致死靶点，如ATR、PRMT5等。这些靶点的抑制剂在克服肿瘤耐药性、提高治疗效果方面显示出良好的潜力。与此同时，人们也正试图通过联合用药策略，如将PARP抑制剂与其他抗肿瘤药物联用，以提高治疗效果。总之，合成致死作为一种具有前景的肿瘤治疗策略，为癌症患者带来了新的希望。随着科研技术的不断发展，相信未来会有更多基于合成致死原理的新型抗肿瘤药物问世，为癌症治疗带来革命性的变革。参考文献： 1.Synthetic lethal strategies for the development of cancer therapeutics. Nat Rev Clin Oncol.2025 Jan;22(1): 公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

临床结果临床1期临床研究

2024-11-22

·PRNewswire

Global Coalition for Adaptive Research Announces Evaluation of AZD1390 in GBM AGILE Trial

AstraZeneca's AZD1390 to Join GBM AGILE, a Registrational-Intent Phase 2/3 Adaptive Platform Trial for Patients with Glioblastoma AZD1390 Arm Will Recruit Patients with Newly Diagnosed Glioblastoma LARKSPUR, Calif., Nov. 22, 2024 /PRNewswire/ -- The Global Coalition for Adaptive Research (GCAR) today announced that they have executed an agreement with AstraZeneca for the evaluation of AstraZeneca's compound, AZD1390, in GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment - NCT03970447), the world's first global adaptive platform trial for glioblastoma. The AZD1390 arm will be evaluated for the treatment of newly diagnosed glioblastoma, with recruitment of patients expected to begin by Q2 2025. Continue Reading GBM AGILE Adaptive Global Innovative Learning Environment Glioblastoma is the most aggressive and common form of primary brain cancer. Treatment options and patient outcomes have seen little progress over the past several decades. Since launching in July 2019, the GBM AGILE trial has evaluated multiple therapies and has screened over 2000 patients at trial locations in six countries. GBM AGILE is designed to more rapidly identify and confirm effective therapies for patients with glioblastoma through response adaptive randomization and a seamless phase 2/3 design. Conceived by over 130 key opinion leaders, GBM AGILE is conducted under a master protocol, allowing multiple therapies or combinations of therapies from different pharmaceutical companies to be evaluated simultaneously against a common control arm. With its innovative design and efficient operational infrastructure, data from GBM AGILE can potentially be used as the foundation for a new drug application (NDA) and biologics license application (BLA) submissions and registrations to the US FDA and other health authorities. Professor Anthony Chalmers, Chair of Clinical Oncology at the University of Glasgow and Dr. Patrick Wen, Director, Center for Neuro-Oncology at Dana-Farber Cancer Institute, and Professor of Neurology at Harvard Medical School, will serve as arm Principal Investigators for AZD1390's evaluation in GBM AGILE. Dr. Timothy Cloughesy, Director, Neuro-Oncology Program and Distinguished Professor of Neurology at the University of California, Los Angeles, is the Global Principal Investigator for the overall study. "There is an urgent need for new, tolerable and effective therapies to treat glioblastoma. GBM AGILE is a revolutionary, patient-centered, potentially registration-enabling, adaptive platform trial for glioblastoma," said Dr. Patrick Wen. "We are excited to include AZD1390 in GBM AGILE, based on encouraging data from previous studies, showing encouraging preliminary efficacy in heavily treated recurrent glioblastoma patients and potential for AZD1390 to act as a radiosensitizer. This investigational drug has the potential to support improved outcomes for glioblastoma patients." AZD1390 is brain penetrant ataxia telangiectasia mutant (ATM) kinase inhibitor that blocks ATM-dependent signaling and repair of DNA double strand breaks (DSBs) in the genome. Preclinically, AZD1390 exhibits activity in combination with agents such as irradiation that induce DSBs. AZD1390 has also been shown to achieve clinically relevant concentrations in resected glioblastoma tissue and suppress the natural repair of the DNA damage that is mediated by radiation. Furthermore, in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024, AZD1390 with radiotherapy showed a manageable safety profile and preliminary efficacy for patients with glioblastoma in a Phase I trial. "GCAR is committed to accelerating the development of life-changing treatments for patients with rare and deadly diseases such as glioblastoma. We believe that adaptive platform trials have the potential to achieve that mission and make a profound difference for patients," said Dr. Meredith Buxton, Chief Executive Officer and President of GCAR. "We are delighted to collaborate with AstraZeneca and look forward to expediting the evaluation of AZD1390 in GBM AGILE for the treatment of glioblastoma, a devastating disease with a critical need for more effective treatments." About Global Coalition for Adaptive Research (GCAR) Global Coalition for Adaptive Research (GCAR) is a 501(c)(3) non-profit corporation uniting physicians, clinical researchers, advocacy and philanthropic organizations, biotech/pharma companies, health authorities, and other key stakeholders in healthcare to expedite the discovery and development of treatments for patients with rare and deadly diseases. As the sponsor of innovative trials, including master protocols and adaptive platform trials, GCAR is dedicated to the advancement of science by modernizing clinical trials that support more efficient, less costly drug development. To learn more about GCAR and its initiatives, visit gcaresearch.org and follow us on social media @GCAResearch. CONTACT: Global Coalition for Adaptive Research Rachel Rosenstein-Sisson [email protected] SOURCE Global Coalition for Adaptive Research 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

100 项与 AZD-1390 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
转移性实体瘤	临床1期	美国	AstraZeneca PLC	2023-05-17
脑转移瘤	临床1期	美国	AstraZeneca PLC	2018-04-02
脑转移瘤	临床1期	日本	AstraZeneca PLC	2018-04-02
脑转移瘤	临床1期	英国	AstraZeneca PLC	2018-04-02
多形性胶质母细胞瘤	临床1期	美国	AstraZeneca PLC	2018-04-02
多形性胶质母细胞瘤	临床1期	日本	AstraZeneca PLC	2018-04-02
多形性胶质母细胞瘤	临床1期	英国	AstraZeneca PLC	2018-04-02
胶质母细胞瘤，IDH野生型	临床1期	美国	AstraZeneca PLC	2018-04-02
胶质母细胞瘤，IDH野生型	临床1期	日本	AstraZeneca PLC	2018-04-02
胶质母细胞瘤，IDH野生型	临床1期	英国	AstraZeneca PLC	2018-04-02

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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


NCT05182905 (CTNI-55, SNO2024)	早期临床1期	复发性胶质母细胞瘤 MGMT-unmethylated	-	AZD1390 120/300mg	夢鏇襯積淵鏇夢願願鬱(願鹹觸鑰鹽蓋構艱積顧) = 15.4 months 糧齋製鑰鑰鹹艱淵餘窪 (壓艱鬱膚廠鹽膚構遞製 ) 更多	积极	2024-11-11
				AZD1390 400mg
NCT05182905 (JS02.5.A, EANO2024)	早期临床1期	复发性胶质母细胞瘤 MGMT-unmethylated	-	AZD1390 120mg	鑰糧遞顧顧齋膚醖蓋鑰(繭夢鹽構積襯繭醖夢窪) = 簾構糧顧鏇廠構鹽簾繭觸觸獵繭鬱艱鹽窪築鏇 (構鹽糧蓋簾夢壓範鬱鏇 )	积极	2024-10-17
				AZD1390 300mg	鑰糧遞顧顧齋膚醖蓋鑰(繭夢鹽構積襯繭醖夢窪) = 願鹽網顧積廠獵網繭夢觸觸獵繭鬱艱鹽窪築鏇 (構鹽糧蓋簾夢壓範鬱鏇 )
NCT03423628 (Phase 1, ASTRO2024)	临床1期	胶质母细胞瘤 O-6-methylguanine-DNA methyltransferase unmethylated	115	AZD1390 + IMRT 35 Gy in 10 fractions over 2 weeks	願製憲壓襯齋鏇觸範襯(淵觸鏇鏇襯醖淵觸淵醖) = 51.3% 鏇廠範襯醖獵廠蓋獵獵 (繭觸醖網選艱鑰憲鹹繭 ) 更多	积极	2024-10-01
				AZD1390 + IMRT 60 Gy in 30 fractions over 6 weeks
NCT05182905 (AACR2024) 人工标引	早期临床1期	胶质母细胞瘤 MGMT	14	AZD1390 plus radiotherapy	鹽窪蓋網鏇餘衊簾獵鏇(鹽繭淵齋積窪淵觸構壓) = 獵齋鑰鏇範艱衊獵鑰觸鹽鑰鑰製選構遞網觸壓 (蓋範窪衊糧膚繭壓願窪 ) 更多	积极	2024-04-05
				AZD1390+ radiotherapy (23-25 hours following the final dose)	鹽窪蓋網鏇餘衊簾獵鏇(鹽繭淵齋積窪淵觸構壓) = 壓壓構繭鹹餘遞鑰顧觸鹽鑰鑰製選構遞網觸壓 (蓋範窪衊糧膚繭壓願窪 ) 更多
NCT05182905 (CTNI-25, SNO2023)	早期临床1期	复发性胶质母细胞瘤 ATM inhibition	17	AZD1390 + Radiotherapy	壓網鬱蓋憲範窪齋鬱鬱(糧醖簾蓋衊構膚廠觸觸) = 觸糧選築鹽齋餘鬱築夢遞艱選鬱願顧鏇壓獵網 (醖壓遞遞鑰製壓憲艱憲 )	积极	2023-11-10
				AZD1390 (Untreated Control)	壓網鬱蓋憲範窪齋鬱鬱(糧醖簾蓋衊構膚廠觸觸) = 選壓製齋構糧鑰製簾觸遞艱選鬱願顧鏇壓獵網 (醖壓遞遞鑰製壓憲艱憲 )
NCT05182905 (ESMO 12023 \| ESMO 22023) 人工标引	早期临床1期	复发性胶质母细胞瘤	12	AZD1390	範壓簾鬱簾顧獵範襯膚(製淵鹹膚簾鹽願膚夢憲) = 壓遞襯鹽鹽蓋廠夢選網獵獵遞艱顧夢積願範製 (壓製廠窪餘築築築簾範 ) 更多	积极	2023-10-21
				untreated controls	壓衊顧構淵蓋蓋淵範鬱(繭製餘遞構艱顧範蓋願) = 顧蓋願齋鬱選鏇壓積鏇艱鏇壓顧襯夢獵顧遞鹽 (鹽艱壓獵積構鏇衊鬱衊 )
NCT03215381 (phase I PET study, EANM2018)	临床1期	-	8	AZD1390	簾願願築糧醖蓋繭鏇築(淵廠鹹醖夢膚鹹選襯壓) = 壓衊鬱鏇積築顧構齋糧餘獵餘糧膚獵築艱夢衊 (遞衊鹽簾糧觸壓構餘鏇, 0.54 ~ 1.33) 更多	-	2018-09-18