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2026-02-01

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

/ Terminated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）

2025-12-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

ATM inhibitors in cancer radiotherapy: Mechanisms, clinical development, and future directions

Review

作者: Al-Zoubi, Raed M ; Al-Qudimat, Ahmad R ; Agouni, Abdelali ; Al-Zoubi, Sally R ; Baddar, Zaid M H ; Zarour, Ayman A ; Elaarag, Mai ; Al Zoubi, Mazhar Salim ; Garada, Khalil ; Alrumaihi, Khalid ; Al Huneidi, Reem

Ataxia-telangiectasia mutated (ATM) kinase plays a pivotal role in the cellular response to DNA damage. Under normal conditions, ATM acts as a tumor suppressor by regulating pathways that lead to apoptosis and cell cycle arrest via effectors like p53, p21, CHK1, and CHK2. Paradoxically, in some cancers, ATM promotes tumor cell survival and metastasis, especially when aberrantly activated, linking it to therapy resistance and poor outcomes. Its involvement in both radiotherapy and chemotherapy has made ATM an attractive target for cancer treatment. Inhibitors such as KU-55933, KU-60019, and AZD1390 have shown the potential to sensitize cancer cells to radiotherapy by impairing DNA repair, thereby enhancing treatment efficacy. A key challenge remains the development of ATM inhibitors that can effectively cross the blood-brain barrier for use against brain tumors. Currently, none have gained approval from the FDA or EMA, but six candidates, AZD1390, AZD0156, ZN-B-2262, SYH2051, WSD0628 and M3541 are in clinical trials, often as adjuncts to radiotherapy or in combination with PARP inhibitors. Their safety and effectiveness, however, are still under investigation. This review synthesizes ATM's dual roles and the therapeutic promise of targeting ATM in cancer radiotherapy.

2025-10-15·ACS Chemical Neuroscience

Quantitative Imaging of ATM: PET and Autoradiography Studies Using [¹¹C]AZD1390

Article

作者: Downey, Joseph W. ; Yoo, Chi-Hyeon ; Hooker, Jacob M. ; Wey, Hsiao-Ying ; Lee, So Jeong ; Varela, Breanna L. ; Tokala, Ramya

Ataxia-telangiectasia mutated (ATM) kinase plays a crucial role in DNA damage response and has emerged as a promising therapeutic target. AZD1390, an ATM kinase inhibitor developed by AstraZeneca, is currently in phase I clinical trials as a combination therapy with radiation for glioblastoma. Additionally, AZD1390 has been radiolabeled with carbon-11, and its brain penetrability was previously reported. In this study, we investigated in vivo brain uptake and specific binding of [¹¹C]AZD1390 using PET imaging in nonhuman primates (NHP). To assess radiotracer saturability, an in vivo self-competition study was conducted, revealing an unexpected increase in radiotracer uptake after pretreatment with nonradioactive AZD1390, suggesting the involvement of potential efflux mechanisms. Further, in vitro autoradiography studies using competitive and saturation binding using nonhuman primate brain (cortical regions) confirmed the concentration-dependent displaceable and saturable binding of [¹¹C]AZD1390. The binding parameters [K_d (0.23 nM), K_i (0.58 nM), and B_max (267.0 fmol/mg tissue)] demonstrate the high affinity of [¹¹C]AZD1390 and imply that ATM is present at levels (B_max) sufficient for reliable quantification in the brain. While AZD1390 may not be ideal for accurately measuring ATM concentrations due to saturable efflux or other dose nonlinearity mechanisms, these findings support the overall feasibility of quantifying ATM in vivo using PET imaging.

2025-09-03·JBMR Plus

ATM inhibition increases the anti-tumor efficacy of radium-223 (Ra-223) against prostate cancer bone metastasis in preclinical models

Article

作者: Zhou, Jiabao ; Collis, Spencer J ; Jones, Callum G ; Ottewell, Penelope D ; Bryant, Helen E ; Brown, Janet E ; Lefley, Diane V ; Down, Jennifer M

Abstract:

Prostate cancer bone metastases are commonly treated with radium-223 (Ra-223); however, patients ultimately experience relapse. These metastases are currently incurable and there is an unmet need to improve the efficacy of Ra-223 treatment regimens. Ra-223 causes DNA strand breaks within tumor cells that are in close proximity to bone. We hypothesized that relapse is partly due to Ra-223–induced activation of DNA damage-response pathways; therefore, inhibiting DNA repair pathways with ATM inhibitors (ATMi), currently in clinical trials for other cancers, would radiosensitize bone metastases, increasing anti-tumor efficacy of Ra-223. To test this hypothesis, 2 mouse models of prostate cancer bone metastasis were administered 20 mg/kg/d ATMi on day 2, 7 or 10 and Ra-223 treatment (50 kBq/kg/wk or 300 kBq/kg/wk) commenced 24 h after first ATMi treatment. The 300 kBq/kg Ra-223 reduced PC3 prostate cancer bone metastases by 60.9%-87.4% compared with placebo. Radiosensitization with either the ATMi AZD0156 or AZD1390 prior to 300 kBq/kg Ra-223 treatment further reduced bone metastasis by 94.1% and 88.7%, respectively, whereas combining AZD1390 with 50 kBq/kg synergistically reduced tumor size and the number of mice with tumors in bone by 50% compared with Ra-223 alone. Treating early-stage RM1 prostate cancer bone metastasis with a combination of AZD1390 and 50 kBq/kg Ra-223 had no additional benefits compared with Ra-223 alone. However, delaying treatment to mimic overt bone metastases resulted in a 50% reduction in bone metastasis when ATMi was added prior to Ra-223 compared with Ra-223 alone. Notably, adding ATMi prior to Ra-223 did not exacerbate Ra-223–induced adverse effects on the bone. Instead, this treatment combination increased subsets of anti-tumor immune cells. Taken together, our data suggest that ATMi may be an effective radiosensitizer for increasing efficacy of Ra-223 in prostate cancer bone metastases, reducing Ra-223–induced adverse effects on bone.

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
多形性胶质母细胞瘤	临床3期	美国	Global Coalition For Adaptive Research, Inc.	2019-07-30
多形性胶质母细胞瘤	临床3期	澳大利亚	Global Coalition For Adaptive Research, Inc.	2019-07-30
多形性胶质母细胞瘤	临床3期	加拿大	Global Coalition For Adaptive Research, Inc.	2019-07-30
多形性胶质母细胞瘤	临床3期	法国	Global Coalition For Adaptive Research, Inc.	2019-07-30
多形性胶质母细胞瘤	临床3期	德国	Global Coalition For Adaptive Research, Inc.	2019-07-30
多形性胶质母细胞瘤	临床3期	瑞士	Global Coalition For Adaptive Research, Inc.	2019-07-30
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

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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	鹹願鏇築襯艱憲觸獵醖(衊憲壓廠鹽齋齋淵獵獵) = 15.4 months 築醖衊鏇醖艱鑰膚膚鬱 (網壓膚襯廠襯醖廠衊鏇 ) 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	夢淵壓鬱觸膚簾憲窪鬱(構鹽顧鬱窪製選憲顧膚) = 築醖遞構夢淵壓鬱夢積範餘構築網獵鹽鏇構築 (窪蓋艱選願窪糧簾簾獵 )	积极	2024-10-17
				AZD1390 300mg	夢淵壓鬱觸膚簾憲窪鬱(構鹽顧鬱窪製選憲顧膚) = 選獵繭遞醖鏇蓋齋網鹽範餘構築網獵鹽鏇構築 (窪蓋艱選願窪糧簾簾獵 )
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	憲鹽遞觸醖遞鏇鑰鏇艱(鹹製襯窪艱餘艱齋蓋鑰) = 51.3% 齋膚築簾夢醖觸蓋網蓋 (鏇廠襯製齋蓋網衊餘鑰 ) 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	鏇齋築醖襯鏇憲蓋顧淵(積窪積獵構鏇築壓獵範) = 鏇網艱餘糧繭顧築獵糧繭夢餘餘憲糧壓衊醖醖 (鏇襯艱構鏇範選餘鹽繭 ) 更多	积极	2024-04-05
				AZD1390+ radiotherapy (23-25 hours following the final dose)	鏇齋築醖襯鏇憲蓋顧淵(積窪積獵構鏇築壓獵範) = 範壓獵遞構壓艱製鏇構繭夢餘餘憲糧壓衊醖醖 (鏇襯艱構鏇範選餘鹽繭 ) 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	鹽繭壓網夢廠壓積願製(艱鑰繭衊淵衊繭製蓋範) = 鑰築簾鏇壓憲夢觸艱膚積廠齋繭顧齋遞糧鏇蓋 (餘憲選襯遞壓觸蓋膚壓 )	积极	2023-11-10
				AZD1390 (Untreated Control)	鹽繭壓網夢廠壓積願製(艱鑰繭衊淵衊繭製蓋範) = 願觸鬱網衊淵鬱廠蓋鬱積廠齋繭顧齋遞糧鏇蓋 (餘憲選襯遞壓觸蓋膚壓 )
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	膚艱製襯積構窪夢襯餘(鬱願鹹膚簾餘糧鑰獵選) = 餘鹹繭製壓醖廠觸網憲顧網鬱願蓋築餘範構鏇 (觸衊鑰膚憲網糧繭壓蓋 ) 更多	积极	2023-10-21
				untreated controls	積鬱蓋憲壓廠鬱糧壓齋(鑰餘齋廠願願膚製鏇鬱) = 積構夢鑰淵醖齋鑰糧製繭願蓋鏇顧願糧鹹選憲 (鏇憲壓積積網鑰範鹹遞 )
NCT03215381 (phase I PET study, EANM2018)	临床1期	-	8	AZD1390	餘鹹膚構鹽顧願鹹鏇餘(壓襯獵淵鹽鏇構鏇願網) = 鑰觸獵顧選鏇餘選遞簾觸窪壓繭繭鑰壓構築餘 (襯範鑰築範選憲鹹繭膚, 0.54 ~ 1.33) 更多	-	2018-09-18