A Phase 3, Randomized, Double-blind, Add-on Study Evaluating the Safety and Efficacy of Navtemadlin Plus Ruxolitinib Vs Placebo Plus Ruxolitinib in JAK Inhibitor-Naïve Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib

This clinical trial is evaluating whether addition of navtemadlin to ruxolitinib treatment will provide more clinical benefit than ruxolitinib alone for patients with Myelofibrosis who have a suboptimal response to ruxolitinib treatment alone.
Subjects will start by receiving ruxolitinib alone in the run-in period. Those who demostrate a suboptimal response from ruxolitinib alone will then be randomized 2:1 to receive navtemadlin or navtemadlin placebo as add-on treatment to their ongoing ruxolitinib. Randomized means that subjects will be assigned to a group by chance, like a flip of a coin. The study is blinded, meaning the subjects, doctors, central endpoint assessors and sponsor will not know which add on treatment (navtemadlin or navtemadlin placebo) the subject is receiving.

开始日期2024-06-03

申办/合作机构

Kartos Therapeutics, Inc.初创企业

CTIS2022-502196-31-00 / Not yet recruiting

A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects with TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy - KRT-232-118

开始日期2023-08-24

申办/合作机构

Kartos Therapeutics, Inc.初创企业

NCT05797831 / Recruiting临床2/3期

A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy

This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete response or partial response on chemotherapy.
The study will be conducted in 2 parts. Part 1 will evaluate safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose. Part 2 will evaluate the efficacy and safety of navtemadlin Phase 3 dose compared to placebo.

开始日期2023-07-17

申办/合作机构

Kartos Therapeutics, Inc.初创企业

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100 项与 Navtemadlin 相关的临床结果

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100 项与 Navtemadlin 相关的转化医学

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100 项与 Navtemadlin 相关的专利（医药）

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项与 Navtemadlin 相关的文献（医药）

2024-11-01·FREE RADICAL BIOLOGY AND MEDICINE

Icariin targets p53 to protect against ceramide-induced neuronal senescence: Implication in Alzheimer's disease

Article

作者: Wu, Beibei ; Zhu, Lemei ; Xiao, Qiao ; Peng, Weijun ; Tang, Hanfen

BACKGROUND:

Alzheimer's disease (AD) is a leading cause of dementia. The aging brain is particularly vulnerable to various stressors, including increased levels of ceramide. However, the role of ceramide in neuronal cell senescence and AD progression and whether icariin, a natural flavonoid glucoside, could reverse neuronal senescence remain inadequately understood.

AIM:

In this study, we explore the role of ceramide in neuronal senescence and AD, and whether icariin can counteract these effects.

METHODS:

We pretreated HT-22 cells with icariin and then induced senescence with ceramide. Various assays were employed to assess cell senescence, such as reactive oxygen species (ROS) production, cell cycle progression, β-galactosidase staining, and expression of senescence-associated proteins. In vivo studies utilized APP/PS1 mice and C57BL/6J mice injected with ceramide to evaluate behavioral changes, histopathological alterations, and senescence-associated protein expression. Transcriptomics, molecular docking, molecular dynamics simulations, and cellular thermal shift assays were employed to verify the interaction between icariin and P53. The specificity of icariin targeting of P53 was further confirmed through rescue experiments utilizing the P53 activator Navtemadlin.

RESULTS:

Our data demonstrated that ceramide could induce neuronal senescence and AD-related pathologies, which were reversed by icariin. Moreover, molecular studies revealed that icariin directly targeted P53, and its neuroprotective effects were attenuated by P53 activation, providing evidence for the role of P53 in icariin-mediated neuroprotection.

CONCLUSION:

Icariin demonstrates a protective effect against ceramide-induced neuronal senescence by inhibiting the P53 pathway. This identifies a novel mechanism of action for icariin, offering a novel therapeutic approach for AD and other age-related neurodegenerative diseases.

2024-09-01·JCO Precision Oncology

Combination of MDM2 and Targeted Kinase Inhibitors Results in Prolonged Tumor Control in Lung Adenocarcinomas With Oncogenic Tyrosine Kinase Drivers and MDM2 Amplification

Article

作者: Elkrief, Arielle ; Liu, Zebing ; Markov, Vladimir ; Bloom, Jamie L. ; Offin, Michael D. ; Smith, Roger S. ; Lui, Allan J.W. ; Ladanyi, Marc ; Khodos, Inna ; Vojnic, Morana ; Somwar, Romel ; Hayashi, Takuo ; Rudin, Charles M. ; Odintsov, Igor ; Riely, Gregory J. ; de Stanchina, Elisa

PURPOSE:

MDM2, a negative regulator of the TP53 tumor suppressor, is oncogenic when amplified. MDM2 amplification (MDM2amp) is mutually exclusive with TP53 mutation and is seen in 6% of patients with lung adenocarcinoma (LUAD), with significant enrichment in subsets with receptor tyrosine kinase (RTK) driver alterations. Recent studies have shown synergistic activity of MDM2 and MEK inhibition in patient-derived LUAD models with MDM2amp and RTK driver alterations. However, the combination of MDM2 and RTK inhibitors in LUAD has not been studied.

METHODS:

We evaluated the combination of MDM2 and RTK inhibition in patient-derived models of LUAD.

RESULTS:

In a RET-fusion LUAD patient-derived model with MDM2amp, MDM2 inhibition with either milademetan or AMG232 combined with selpercatinib resulted in long-term in vivo tumor control markedly superior to either agent alone. Similarly, in an EGFR-mutated model with MDM2amp, combining either milademetan or AMG232 with osimertinib resulted in long-term in vivo tumor control, which was strikingly superior to either agent alone.

CONCLUSION:

These preclinical in vivo data provide a rationale for further clinical development of this combinatorial targeted therapy approach.

2023-05-12·Cellular and molecular life sciences : CMLS

Single-cell molecular profiling using ex vivo functional readouts fuels precision oncology in glioblastoma.

Article

作者: Solie, Lien ; Ligon, Keith L ; Bosisio, Francesca M ; Claeys, Annelies ; Cole, Basiel ; Antoranz, Asier ; Cohen, Elizabeth F ; Tolstorukov, Michael Y ; De Vleeschouwer, Steven ; Saeys, Yvan ; De Smet, Frederik ; Sciot, Raf ; Put, Eric ; Creemers, Pieter-Jan ; Derweduwe, Marleen ; Verfaillie, Michiel ; Van Gassen, Sofie ; Bamps, Sven ; Van der Planken, David ; Nazari, Pouya ; Panovska, Dena ; Verbeke, Tatjana ; Clement, Paul M

BACKGROUND:

Functional profiling of freshly isolated glioblastoma (GBM) cells is being evaluated as a next-generation method for precision oncology. While promising, its success largely depends on the method to evaluate treatment activity which requires sufficient resolution and specificity.

METHODS:

Here, we describe the 'precision oncology by single-cell profiling using ex vivo readouts of functionality' (PROSPERO) assay to evaluate the intrinsic susceptibility of high-grade brain tumor cells to respond to therapy. Different from other assays, PROSPERO extends beyond life/death screening by rapidly evaluating acute molecular drug responses at single-cell resolution.

RESULTS:

The PROSPERO assay was developed by correlating short-term single-cell molecular signatures using mass cytometry by time-of-flight (CyTOF) to long-term cytotoxicity readouts in representative patient-derived glioblastoma cell cultures (n = 14) that were exposed to radiotherapy and the small-molecule p53/MDM2 inhibitor AMG232. The predictive model was subsequently projected to evaluate drug activity in freshly resected GBM samples from patients (n = 34). Here, PROSPERO revealed an overall limited capacity of tumor cells to respond to therapy, as reflected by the inability to induce key molecular markers upon ex vivo treatment exposure, while retaining proliferative capacity, insights that were validated in patient-derived xenograft (PDX) models. This approach also allowed the investigation of cellular plasticity, which in PDCLs highlighted therapy-induced proneural-to-mesenchymal (PMT) transitions, while in patients' samples this was more heterogeneous.

CONCLUSION:

PROSPERO provides a precise way to evaluate therapy efficacy by measuring molecular drug responses using specific biomarker changes in freshly resected brain tumor samples, in addition to providing key functional insights in cellular behavior, which may ultimately complement standard, clinical biomarker evaluations.

项与 Navtemadlin 相关的新闻（医药）

2023-04-12

·SYNAPSE

p53 Y220C能否开辟靶向p53新方向

转录因子和肿瘤抑制蛋白p53是癌症中最常突变和失活的基因。目前恢复癌细胞的p53功能主要有2种策略：(1) 对于p53野生型的癌细胞，抑制p53的负调节因子；(2) 对于p53已突变的癌细胞，恢复p53活性。通过靶向wt-p53的负调控因子MDM2和MDMX重新激活wt-p53已经取得了许多进展。如图2所示，MDM2/MDMX抑制剂(RG7388, MI77301, DS3032, HDM201, MK4688, AMG232和APG115等)使得p53在未突变的癌症中激活。这些小分子多处于临床后期，如安进的AMG232和罗氏的RG7388分别处于临床三期用于治疗骨髓纤维化和急性髓性白血病。但是大约50%的人类癌症含有突变的p53, MDM2/MDMX抑制剂和MDM2降解剂都不能使突变的p53重新激活。p53突变通常会导致wt-p53功能的丧失，在某些情况下，会导致致癌功能的增加。功能的丧失是由于突变的p53无法与DNA结合，因为失去了与DNA的残基接触，并且失去了折叠成与DNA结合所需的活性构象的能力。因此，直接靶向p53蛋白是一种非常有吸引力的抗癌治疗策略。但是，p53蛋白经常被认为是“不可靶向的”，因为wt-p53和突变p53都没有结合口袋或变构位点，因而不容易被小分子靶向。在有TP53基因突变的人类癌症中，75%是错义突变，主要发生在p53的DBD。（见图3）这些突变大多发生在“热点”残基中，这些残基的变化要么导致与DNA失去接触，要么导致p53蛋白结构稳定性的变化。因此，突变体可分为接触突变体和结构突变体。接触突变体涉及直接与DNA相互作用的残基，为了有效靶向，引入相互作用来补偿缺失的DNA接触是必要的。由于在这些接触p53突变体中缺乏合适的结合口袋，用小分子靶向它们非常具有挑战性。另一方面，结构突变体存在残留突变，影响p53的热稳定性和结构，使突变体在生理温度下不稳定，无法实现正确的折叠和具有wt-like功能。这些热点突变的结构特征显示p53 Y220C中有一个可靶向的空腔，该突变通过DBD中热稳定性的丧失间接抑制DNA结合。随后，一些小分子如PhiKan083被开发出来与p53 Y220C腔结合，并经历了几次化学迭代，以提高亲和性和热稳定性。虽然PhiKan化合物已经证明了p53 Y220C的潜在靶向性，但没有一个达到生化效力或表现出WT水平的热稳定性，因此它们目前的形式不太可能满足候选药物的要求。 PMVPharma报道了小分子激活剂PC14586，其结构尚未披露，但可以与Y220C口袋特异性结合，这是第一个进入临床试验的Y220C重新活化剂。临床前数据显示，PC14586可诱导Y220C p53突变肿瘤的异种移植模型中的肿瘤消退，且在Y220C突变淋巴瘤和肉瘤肿瘤产生的细胞系中的IC50为~192-722nM。此外，当PC14586与抗PD-1疗法相结合时，表现出协同抗肿瘤作用。根据PC14586一期临床试验的结果。安全性层面看，最常见的治疗引发的不良事件(>15%)包括恶心、呕吐、AST升高、ALT升高、贫血、血肌酐升高和疲劳。最大耐受剂量(MTD)为1500mg，每日2次。有效性层面看，研究人员根据RECIST v1.1评估，初始日总剂量为1150 mg及以上的患者的ORR为32%(8/25)。在8例有应答的患者中，6例已证实部分应答，2例未证实部分应答，尚待确诊。所有剂量队列的ORR为24%(8/33)。在6种不同的肿瘤类型中观察到反应，包括乳腺癌、子宫内膜癌、前列腺癌、胰腺癌、卵巢癌和小细胞肺癌。当剂量≥1150mg时，在19/25的患者中观察到疾病稳定或部分缓解的最佳反应(76%)。 PMV Pharma首席医疗官Leila Alland医学博士说:“这些令人鼓舞的一期安全性和初步疗效数据证明了PC14586作为单一疗法在多种肿瘤类型中选择性地重新激活p53的概念”。PMV Pharma也将在2023年初启动研究的潜在关键的第二阶段部分。打开智慧芽新药情报库，搜索关键词p53 Y220C，可以看到6条药物信息。其中，PC-14586处于临床1/2期；加科思的JAB-30300、MRC Laboratory公司的MB-710和MB-725、剑桥大学的PK-083、PK-9318均处于临床前。在智慧芽专利数据库中搜索关键词p53 Y220C，PMV Pharma围绕着这一靶点申请了11篇专利，涵盖了化合物专利、用途专利、P53突变检测方法专利、小分子与P53蛋白共晶专利等。最早的一篇专利来自WO2017143291，公开了一类带炔基取代的吲哚类化合物。最新的一篇专利US2023024905，公开了这类带炔基取代的吲哚类化合物与P53蛋白共晶。国内方面，加科思公司在官网上介绍JAB-30300已经启动了IND研究。总结半胱氨酸活性KRASG12C抑制剂sotorasib的发现和FDA批准上市证明了共价靶向缺乏典型配体结合口袋的蛋白质中的体细胞突变半胱氨酸的治疗潜力。通过丙烯酰胺-半胱氨酸迈克尔加成反应的动力学克服了KRAS G12C抑制剂的弱可逆亲和力，从而获得了较高的生化效力。而通过与p53 Y220C中体细胞半胱氨酸发生选择性反应的共价化合物，可将其热稳定性恢复到WT水平。靶向p53 Y220C突变体的激动剂作为一种新型治疗策略，有望每年治疗超过125,000名携带p53 Y220C突变的癌症患者，并作为一种预防性治疗，以降低Li-Fraumeni综合征的癌症风险。参考资料： 1.Scott W. Lowe, et al; Putting p53 in Context.http://dx.doi.org.libproxy1.nus.edu.sg/10.1016/j.cell.2017.08.028. 2.Angelo Aguilar; Shaomeng Wang. Therapeutic Strategies to Activate p53.Pharmaceuticals 2023, 16, 24. 3.Alison M. Schram et.al. First-in-Human Study of PC14586, a Small Molecule Structural Corrector of Y220C Mutant p53, in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation. ASCO Annual Meeting. 2022. 4.David P. Lane1;Chandra S. Verma. Covalent Rescue of Mutant p53. Cancer Discov 2023;13:14–6. 5.智慧芽新药情报库.

临床研究临床申请细胞疗法

2023-04-12

·智慧芽新药科讯

p53 Y220C能否开辟靶向p53新方向

转录因子和肿瘤抑制蛋白p53是癌症中最常突变和失活的基因。目前恢复癌细胞的p53功能主要有2种策略：(1) 对于p53野生型的癌细胞，抑制p53的负调节因子；(2) 对于p53已突变的癌细胞，恢复p53活性。图1 p53相关靶点药物研发策略通过靶向wt-p53的负调控因子MDM2和MDMX重新激活wt-p53已经取得了许多进展。如图2所示，MDM2/MDMX抑制剂(RG7388, MI77301, DS3032, HDM201, MK4688, AMG232和APG115等)使得p53在未突变的癌症中激活。这些小分子多处于临床后期，如安进的AMG232和罗氏的RG7388分别处于临床三期用于治疗骨髓纤维化和急性髓性白血病。但是大约50%的人类癌症含有突变的p53, MDM2/MDMX抑制剂和MDM2降解剂都不能使突变的p53重新激活。p53突变通常会导致wt-p53功能的丧失，在某些情况下，会导致致癌功能的增加。功能的丧失是由于突变的p53无法与DNA结合，因为失去了与DNA的残基接触，并且失去了折叠成与DNA结合所需的活性构象的能力。图2 MDM2抑制剂的化学结构因此，直接靶向p53蛋白是一种非常有吸引力的抗癌治疗策略。但是，p53蛋白经常被认为是“不可靶向的”，因为wt-p53和突变p53都没有结合口袋或变构位点，因而不容易被小分子靶向。在有TP53基因突变的人类癌症中，75%是错义突变，主要发生在p53的DBD。（见图3）这些突变大多发生在“热点”残基中，这些残基的变化要么导致与DNA失去接触，要么导致p53蛋白结构稳定性的变化。因此，突变体可分为接触突变体和结构突变体。接触突变体涉及直接与DNA相互作用的残基，为了有效靶向，引入相互作用来补偿缺失的DNA接触是必要的。由于在这些接触p53突变体中缺乏合适的结合口袋，用小分子靶向它们非常具有挑战性。另一方面，结构突变体存在残留突变，影响p53的热稳定性和结构，使突变体在生理温度下不稳定，无法实现正确的折叠和具有wt-like功能。图3 突变型p53热点突变这些热点突变的结构特征显示p53 Y220C中有一个可靶向的空腔，该突变通过DBD中热稳定性的丧失间接抑制DNA结合。随后，一些小分子如PhiKan083被开发出来与p53 Y220C腔结合，并经历了几次化学迭代，以提高亲和性和热稳定性。虽然PhiKan化合物已经证明了p53 Y220C的潜在靶向性，但没有一个达到生化效力或表现出WT水平的热稳定性，因此它们目前的形式不太可能满足候选药物的要求。PMVPharma报道了小分子激活剂PC14586，其结构尚未披露，但可以与Y220C口袋特异性结合，这是第一个进入临床试验的Y220C重新活化剂。图4 一期临床方案设置临床前数据显示，PC14586可诱导Y220C p53突变肿瘤的异种移植模型中的肿瘤消退，且在Y220C突变淋巴瘤和肉瘤肿瘤产生的细胞系中的IC50为~192-722nM。此外，当PC14586与抗PD-1疗法相结合时，表现出协同抗肿瘤作用。根据PC14586一期临床试验的结果。安全性层面看，最常见的治疗引发的不良事件(>15%)包括恶心、呕吐、AST升高、ALT升高、贫血、血肌酐升高和疲劳。最大耐受剂量(MTD)为1500mg，每日2次。有效性层面看，研究人员根据RECIST v1.1评估，初始日总剂量为1150 mg及以上的患者的ORR为32%(8/25)。在8例有应答的患者中，6例已证实部分应答，2例未证实部分应答，尚待确诊。所有剂量队列的ORR为24%(8/33)。在6种不同的肿瘤类型中观察到反应，包括乳腺癌、子宫内膜癌、前列腺癌、胰腺癌、卵巢癌和小细胞肺癌。当剂量≥1150mg时，在19/25的患者中观察到疾病稳定或部分缓解的最佳反应(76%)。PMV Pharma首席医疗官Leila Alland医学博士说:“这些令人鼓舞的一期安全性和初步疗效数据证明了PC14586作为单一疗法在多种肿瘤类型中选择性地重新激活p53的概念”。PMV Pharma也将在2023年初启动研究的潜在关键的第二阶段部分。图5 p53 Y220C相关药物信息打开智慧芽新药情报库，搜索关键词p53 Y220C，可以看到6条药物信息。其中，PC-14586处于临床1/2期；加科思的JAB-30300、MRC Laboratory公司的MB-710和MB-725、剑桥大学的PK-083、PK-9318均处于临床前。在智慧芽专利数据库中搜索关键词p53 Y220C，PMV Pharma围绕着这一靶点申请了11篇专利，涵盖了化合物专利、用途专利、P53突变检测方法专利、小分子与P53蛋白共晶专利等。最早的一篇专利来自WO2017143291，公开了一类带炔基取代的吲哚类化合物。最新的一篇专利US2023024905，公开了这类带炔基取代的吲哚类化合物与P53蛋白共晶。国内方面，加科思公司在官网上介绍JAB-30300已经启动了IND研究。总结半胱氨酸活性KRAS G12C抑制剂sotorasib的发现和FDA批准上市证明了共价靶向缺乏典型配体结合口袋的蛋白质中的体细胞突变半胱氨酸的治疗潜力。通过丙烯酰胺-半胱氨酸迈克尔加成反应的动力学克服了KRAS G12C抑制剂的弱可逆亲和力，从而获得了较高的生化效力。图6 TP53 Y220C在常见实体瘤中的表达频率而通过与p53 Y220C中体细胞半胱氨酸发生选择性反应的共价化合物，可将其热稳定性恢复到WT水平。靶向p53 Y220C突变体的激动剂作为一种新型治疗策略，有望每年治疗超过125,000名携带p53 Y220C突变的癌症患者，并作为一种预防性治疗，以降低Li-Fraumeni综合征的癌症风险。参考资料：1.Scott W. Lowe, et al; Putting p53 in Context.http://dx.doi.org.libproxy1.nus.edu.sg/10.1016/j.cell.2017.08.028.2.Angelo Aguilar; Shaomeng Wang. Therapeutic Strategies to Activate p53.Pharmaceuticals 2023, 16, 24.3.Alison M. Schram et.al. First-in-Human Study of PC14586, a Small Molecule Structural Corrector of Y220C Mutant p53, in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation. ASCO Annual Meeting. 2022.4.David P. Lane1;Chandra S. Verma. Covalent Rescue of Mutant p53. Cancer Discov 2023;13:14–6.5.智慧芽新药情报库.

临床1期临床3期临床终止临床2期

2023-03-02

·BioSpace

Kartos Therapeutics Appoints Dr. Srdan Verstovsek as Chief Medical Officer

World-Renowned Physician-Scientist and Global Expert in Myeloproliferative Neoplasms Will Be Instrumental in Advancing the Development of Navtemadlin and Other Innovative Therapies to Improve the Lives of Cancer Patients REDWOOD CITY, Calif.--(BUSINESS WIRE)-- Kartos Therapeutics, Inc. (“Kartos” or the “Company”), a clinical stage biopharmaceutical company dedicated to the development of novel, targeted therapeutics that meaningfully improve the lives of patients with cancer, today announced that Dr. Srdan (Serge) Verstovsek, MD, PhD, has been named Chief Medical Officer (CMO). Dr. Verstovsek is a world-renowned physician-scientist and a leading global authority on the treatment of myeloproliferative neoplasms (MPN), including myelofibrosis (MF). Since 1998, Dr. Verstovsek has been affiliated with the University of Texas MD Anderson Cancer Center where he served as hematologist-oncologist and more recently as the United Energy Resources, Inc. Professor of Medicine. He was also Director of the world’s largest MPN clinical research center, the Hanns A. Pielenz Clinical Research Center for MPNs, and Chief of the Section for MPNs. Dr. Verstovsek has collaborated extensively with Kartos in recent years and has been actively involved in all the company’s MPN clinical studies. In his new role, he will assume scientific leadership for the continued development of Kartos’ potential best-in-class MDM2 inhibitor, navtemadlin, currently in clinical development for the treatment of blood cancers and solid tumors, as well as other therapeutics the company is developing. Dr. Verstovsek has achieved international acclaim for pioneering practice-changing therapeutic advances for the treatment of MPNs. He has led more than 80 early/advanced phase clinical trials of novel MPN drugs, including ruxolitinib, which until 2019 was the only FDA-approved medication for myelofibrosis. He has published 24 book chapters, more than 600 peer-reviewed original articles/reviews in leading medical journals and has received numerous clinical research awards. “We are humbled that Dr. Serge Verstovsek has decided to continue his extraordinary career as part of the Kartos team,” said Jesse McGreivy, MD, Chief Executive Officer of Kartos Therapeutics. “Serge’s deep understanding of MPNs and his accomplishments as a clinician and drug developer are unparalleled. Having Serge onboard will be tremendously impactful in our quest to bring navtemadlin and other innovative medicines to patients across the globe.” “I am thrilled to join a Company so dedicated to developing novel, targeted therapeutics that meaningfully improve the lives of patients with cancer,” said Dr. Verstovsek. “Having worked closely with Kartos’ outstanding executive team and been deeply involved in designing several of the company’s studies, I know firsthand about the incredible talent and science driving the development of navtemadlin. I am very enthusiastic about the clinical potential of this groundbreaking drug and look forward to devoting the next stage of my career to help ensure its complete success.” Dr. Verstovsek is a member of the American Society for Clinical Investigation and is co-founder and an Executive Committee Member of the International Working Group for MF Treatment and Research. Dr. Verstovsek received his MD and PhD from the University of Zagreb, Croatia. About Kartos Therapeutics Kartos Therapeutics is a clinical stage biopharmaceutical company with a potential best-in-class MDM2 inhibitor, navtemadlin, in clinical development across a variety of TP53 wild-type hematological malignancies and solid tumors. To learn more, visit and connect with us on LinkedIn.

上市批准高管变更

100 项与 Navtemadlin 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15299

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
复发性子宫内膜癌	临床3期	美国	Kartos Therapeutics, Inc.初创企业	2023-07-17
复发性子宫内膜癌	临床3期	奥地利	Kartos Therapeutics, Inc.初创企业	2023-07-17
复发性子宫内膜癌	临床3期	加拿大	Kartos Therapeutics, Inc.初创企业	2023-07-17
复发性子宫内膜癌	临床3期	丹麦	Kartos Therapeutics, Inc.初创企业	2023-07-17
复发性子宫内膜癌	临床3期	爱沙尼亚	Kartos Therapeutics, Inc.初创企业	2023-07-17
复发性子宫内膜癌	临床3期	芬兰	Kartos Therapeutics, Inc.初创企业	2023-07-17
复发性子宫内膜癌	临床3期	格鲁吉亚	Kartos Therapeutics, Inc.初创企业	2023-07-17
复发性子宫内膜癌	临床3期	匈牙利	Kartos Therapeutics, Inc.初创企业	2023-07-17
复发性子宫内膜癌	临床3期	以色列	Kartos Therapeutics, Inc.初创企业	2023-07-17
复发性子宫内膜癌	临床3期	意大利	Kartos Therapeutics, Inc.初创企业	2023-07-17

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临床结果

适应症

分期

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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


EHA2023	N/A	骨髓增生性疾病	-	Navtemadlin	齋醖夢糧簾壓鏇蓋餘製(鬱鬱選簾淵願簾製襯鏇) = 鬱齋壓餘繭膚願製餘範鹹鹹築遞觸顧鹽顧夢觸 (簾衊夢壓壓選顧鹽選鏇 ) 更多	-	2023-06-08
EHA2023	N/A	骨髓增生性疾病	-	Decitabine	齋醖夢糧簾壓鏇蓋餘製(鬱鬱選簾淵願簾製襯鏇) = 鑰艱選繭願糧網製膚醖鹹鹹築遞觸顧鹽顧夢觸 (簾衊夢壓壓選顧鹽選鏇 ) 更多	-	2023-06-08
NCT04655118 \| NCT05280509 \| NCT04640532 (EHA2023)	N/A	-	-	TL-895	夢選製繭繭顧襯糧顧蓋(願廠夢鏇顧壓獵鹹觸繭) = 選夢壓積夢遞蓋積選鹽襯憲夢鏇糧範醖積顧鑰 (餘蓋積積繭廠簾觸築廠 ) 更多	-	2023-06-08
NCT04485260 (EHA2023)	临床1/2期	原发性骨髓纤维化	32	Navtemadlin + Ruxolitinib	遞簾獵願遞廠範鹽廠願(糧選鹽齋艱襯淵築夢願) = 積觸簾繭艱鹹膚壓艱獵憲襯築鹹築鏇網觸製選 (鬱襯蓋餘顧廠獵膚壓願 ) 更多	-	2023-06-08
NCT03662126 (BOREAS, EHA2023)	临床3期	蕈样真菌病	113	Nvtm 120 mg QD	鑰襯構繭淵膚醖顧夢鏇(構顧膚餘憲願鹽鑰願膚) = 鑰鑰膚鬱齋衊選鏇憲餘獵衊製鏇遞齋衊窪簾選 (廠願鹹廠艱淵遞夢襯製 ) 更多	-	2023-06-08
NCT03787602 (NOTOS, ASCO2023)	临床1/2期	梅克尔细胞癌	-	Navtemadlin 180 mg QD	繭鑰憲選醖構鬱繭遞鑰(鑰鏇顧鹽壓壓夢襯製廠) = 鬱衊觸鹽齋範鹽鬱餘齋襯築顧蓋蓋觸淵廠鬱築 (鑰夢壓範醖夢鬱窪憲餘 ) 更多	积极	2023-05-31
NCT03787602 (ASCO2022) 人工标引	临床1/2期	梅克尔细胞癌 TP53 Wild-type	29	Navtemadlin 240 mg (7D on/ 14D off)	鹹繭窪簾觸膚衊觸願艱(願齋膚壓鹹醖範壓鹽簾) = 窪醖憲鹹餘衊鑰醖觸構壓鹽壓憲顧壓廠顧醖蓋 (膚膚夢簾鏇積製齋醖蓋 ) 更多	积极	2022-06-02
NCT03787602 (ASCO2022) 人工标引	临床1/2期	梅克尔细胞癌 TP53 Wild-type	29	Navtemadlin 240 mg (5D on/ 23D off)	鹹繭窪簾觸膚衊觸願艱(願齋膚壓鹹醖範壓鹽簾) = 淵鏇膚築夢窪遞願築蓋壓鹽壓憲顧壓廠顧醖蓋 (膚膚夢簾鏇積製齋醖蓋 ) 更多	积极	2022-06-02
NCT03217266 (NRG-DT001, ASCO2022) 人工标引	临床1期	软组织肉瘤新辅助	-	Navtemadlin	願範遞鹹襯鏇鹽簾齋觸(艱蓋構築壓廠淵廠淵糧) = 120 mg 5x/week 憲醖觸選願窪製願餘積 (鬱襯鏇範衊壓築艱繭構 )	积极	2022-06-02
NCT02110355 (Pubmed) 人工标引	临床1期	转移性黑色素瘤 TP53-wild type	31	dabrafenib+trametinib+AMG 232	艱夢製壓獵簾鹽遞鬱糧(鏇鏇憲齋襯衊範廠齋壓) = 鑰鏇襯願醖艱製齋壓淵鬱獵憲獵艱範繭顧遞鬱 (範蓋範遞積製膚齋網鑰 ) 更多	积极	2022-05-30
NCT02110355 (Pubmed) 人工标引	临床1期	转移性黑色素瘤 TP53-wild type	31	trametinib	艱夢製壓獵簾鹽遞鬱糧(鏇鏇憲齋襯衊範廠齋壓) = 憲壓願齋夢構鬱艱遞襯鬱獵憲獵艱範繭顧遞鬱 (範蓋範遞積製膚齋網鑰 ) 更多	积极	2022-05-30
NCT01723020 (Pubmed \| Invest New Drugs) 人工标引	临床1期	晚期恶性实体瘤 \| 多发性骨髓瘤 TP53 Wild-type	107	AMG 232	鏇壓夢蓋範積積蓋鏇構(構遞蓋願醖遞顧鏇網遞) = diarrhea, nausea, vomiting, fatigue, decreased appetite, and anemia 憲範壓窪壓選齋範衊壓 (壓廠蓋鏇觸顧觸廠繭艱 ) 更多	积极	2020-06-01
NCT03787602 (ASCO2020)	临床2期	梅克尔细胞癌	11	KRT-232 180mg QD 5/28d	範齋網築鑰夢齋鹽願淵(鑰顧膚壓艱蓋鹽淵願顧) = 選構獵艱蓋遞鑰鬱選蓋範艱顧衊選壓範夢鑰齋 (繭衊鹽網鏇淵襯窪簾襯 )	积极	2020-05-25