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

[+2]

NCT05705466 / Withdrawn临床1/2期

A Two-Part, Phase 1b/2, Multicenter, Open-Label, Dose Escalation and Double-Blind, Randomized, Placebo-Controlled, Dose Expansion Study of the Safety, Efficacy and Pharmacokinetics of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Subjects With Locally Advanced and Metastatic Non-Small Cell Lung Cancer

This study evaluates Navtemadlin (KRT-232) in combination with Pembrolizumab as a maintenance therapy in patients with locally advanced and metastatic non small cell lung cancer.

开始日期2023-06-01

申办/合作机构

Kartos Therapeutics, Inc.初创企业

NCT05027867 / Terminated临床2期

An Open-Label, Multicenter, Phase 2 Study of the Safety and Efficacy of KRT-232 in Subjects With Relapsed or Refractory Small Cell Lung Cancer (SCLC)

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with relapsed or refractory small cell lung cancer.
This study will be conducted in 2 parts. Part 1 will evaluate two treatment arms, each with a different KRT-232 dose. Part 2 will continue the evaluation of the selected treatment arms from Part 1.

开始日期2021-12-06

申办/合作机构

Kartos Therapeutics, Inc.初创企业

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）

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 ; Bosisio, Francesca M ; Ligon, Keith L ; 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 ; Van Gassen, Sofie ; Verfaillie, Michiel ; 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.

2023-04-01·Clinical Lymphoma Myeloma and Leukemia

SOHO State of the Art Updates and Next Questions: Novel Therapeutic Strategies in Development for Myelofibrosis

Review

作者: Verstovsek, Srdan ; Chifotides, Helen T ; Masarova, Lucia

Development of myelofibrosis (MF) therapeutics has reached fruition as the transformative impact of JAK2 inhibitors in the MPN landscape is complemented/expanded by a profusion of novel monotherapies and rational combinations in the frontline and second line settings. Agents in advanced clinical development span various mechanisms of action (eg, epigenetic or apoptotic regulation), may address urgent unmet clinical needs (cytopenias), increase the depth/duration of spleen and symptom responses elicited by ruxolitinib, improve other aspects of the disease besides splenomegaly/constitutional symptoms (eg, resistance to ruxolitinib, bone marrow fibrosis or disease course), provide personalized strategies, and extend overall survival (OS). Ruxolitinib had a dramatic impact on the quality of life and OS of MF patients. Recently, pacritinib received regulatory approval for severely thrombocytopenic MF patients. Momelotinib is advantageously poised among JAK inhibitors given its differentiated mode of action (suppression of hepcidin expression). Momelotinib demonstrated significant improvements in anemia measures, spleen responses, and MF-associated symptoms in MF patients with anemia; and will likely receive regulatory approval in 2023. An array of other novel agents combined with ruxolitinib, such as pelabresib, navitoclax, parsaclisib, or as monotherapies (navtemadlin) are evaluated in pivotal phase 3 trials. Imetelstat (telomerase inhibitor) is currently evaluated in the second line setting; OS was set as the primary endpoint, marking an unprecedented goal in MF trials, wherein SVR35 and TSS50 at 24 weeks have been typical endpoints heretofore. Transfusion independence may be considered another clinically meaningful endpoint in MF trials given its correlation with OS. Overall, therapeutics are at the cusp of an exponential expansion and advancements that will likely lead to the golden era in treatment of MF.

2023-03-20·Scientific reports

MDM2 inhibitors, nutlin-3a and navtemadelin, retain efficacy in human and mouse cancer cells cultured in hypoxia.

Article

作者: Wermeling, Fredrik ; Sedimbi, Saikiran ; Boqvist, Paula Lafqvist ; Ingelshed, Katrine ; Lerma Clavero, Ada ; Jiang, Long ; Bosdotter, Cecilia ; Kannan, Pavitra ; Vojtesek, Borivoj ; Lane, David P

Activation of p53 by small molecule MDM2 inhibitors can induce cell cycle arrest or death in p53 wildtype cancer cells. However, cancer cells exposed to hypoxia can develop resistance to other small molecules, such as chemotherapies, that activate p53. Here, we evaluated whether hypoxia could render cancer cells insensitive to two MDM2 inhibitors with different potencies, nutlin-3a and navtemadlin. Inhibitor efficacy and potency were evaluated under short-term hypoxic conditions in human and mouse cancer cells expressing different p53 genotypes (wild-type, mutant, or null). Treatment of wild-type p53 cancer cells with MDM2 inhibitors reduced cell growth by > 75% in hypoxia through activation of the p53-p21 signaling pathway; no inhibitor-induced growth reduction was observed in hypoxic mutant or null p53 cells except at very high concentrations. The concentration of inhibitors needed to induce the maximal p53 response was not significantly different in hypoxia compared to normoxia. However, inhibitor efficacy varied by species and by cell line, with stronger effects at lower concentrations observed in human cell lines than in mouse cell lines grown as 2D and 3D cultures. Together, these results indicate that MDM2 inhibitors retain efficacy in hypoxia, suggesting they could be useful for targeting acutely hypoxic cancer cells.

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/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/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

适应症	最高研发状态	国家/地区	公司
原发性血小板增多症后骨髓纤维化	临床3期	中国台湾更多	Kartos Therapeutics, Inc.初创企业更多
真性红细胞增多症后骨髓纤维化	临床3期	西班牙更多	Kartos Therapeutics, Inc.初创企业更多
原发性骨髓纤维化	临床3期	加拿大更多	Kartos Therapeutics, Inc.初创企业更多
复发性子宫内膜癌	临床3期	匈牙利更多	Kartos Therapeutics, Inc.初创企业更多
真性红细胞增多症	临床2期	美国更多	Kartos Therapeutics, Inc.初创企业更多

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临床结果

适应症

分期

评价

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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


NCT03662126 (BOREAS, EHA2023)	临床3期	蕈样真菌病	113	Nvtm 120 mg QD	蓋觸膚膚醖憲範淵鬱鏇(夢廠範壓築鑰糧鏇壓窪) = 積壓廠襯選觸鹽顧衊鬱願觸鬱艱艱窪構網餘壓 (觸簾獵鹹鹽壓獵壓鑰願 ) 更多	-	2023-06-08
EHA2023	N/A	骨髓增生性疾病	-	Navtemadlin	鏇蓋網願觸範襯蓋夢範(鬱鹹構網積範網糧鑰遞) = 獵積網鏇艱繭鏇範餘網襯築衊襯夢鑰醖範艱繭 (憲憲艱憲衊鹽膚簾鬱壓 ) 更多	-	2023-06-08
EHA2023	N/A	骨髓增生性疾病	-	Decitabine	鏇蓋網願觸範襯蓋夢範(鬱鹹構網積範網糧鑰遞) = 醖製淵蓋鏇鑰築鹽鹽鹽襯築衊襯夢鑰醖範艱繭 (憲憲艱憲衊鹽膚簾鬱壓 ) 更多	-	2023-06-08
NCT04485260 (EHA2023)	临床1/2期	原发性骨髓纤维化	32	Navtemadlin + Ruxolitinib	鹹夢鑰網蓋醖齋襯構網(衊壓網膚齋築顧鑰觸廠) = 積餘夢觸糧簾築顧憲獵繭願鑰觸醖衊廠範襯醖 (醖餘膚顧鹽糧遞糧顧簾 ) 更多	-	2023-06-08
NCT03787602 (NOTOS, ASCO2023)	临床1/2期	梅克尔细胞癌	-	Navtemadlin 180 mg QD	繭鏇齋鑰獵觸鏇顧糧範(網糧願遞廠夢製糧膚齋) = 糧壓範淵齋網鹽壓網選艱淵鏇顧顧築積積築遞 (鹽網衊鹹廠築廠齋顧艱 ) 更多	积极	2023-05-31
NCT03217266 (NRG-DT001, ASCO2022) 人工标引	临床1期	软组织肉瘤新辅助	-	Navtemadlin	夢廠製襯築選壓觸範衊(顧艱艱鹹遞醖壓積築憲) = 120 mg 5x/week 製遞夢夢積選憲繭鬱遞 (範範積艱襯衊齋構積選 )	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 (7D on/ 14D off)	憲獵鬱積願簾膚遞糧醖(鹽壓積鏇夢淵醖觸襯鹽) = 糧製醖夢製餘鬱築夢鬱鏇範鑰願淵鏇鹹鏇製簾 (醖窪憲願鹽廠膚範顧鑰 ) 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)	憲獵鬱積願簾膚遞糧醖(鹽壓積鏇夢淵醖觸襯鹽) = 獵願廠製壓簾艱壓鑰蓋鏇範鑰願淵鏇鹹鏇製簾 (醖窪憲願鹽廠膚範顧鑰 ) 更多	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	製製糧遞餘鏇鑰餘蓋願(齋餘餘淵獵膚願遞顧廠) = 獵鬱鹽鹽蓋糧齋鹹觸選繭衊觸蓋壓鹹壓構顧鏇 (選衊鹽糧膚餘襯簾淵醖 ) 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	製製糧遞餘鏇鑰餘蓋願(齋餘餘淵獵膚願遞顧廠) = 衊夢構願築鏇膚糧鹽顧繭衊觸蓋壓鹹壓構顧鏇 (選衊鹽糧膚餘襯簾淵醖 ) 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	製餘範壓鬱醖製糧鑰遞(製顧憲觸網蓋選鹹顧齋) = diarrhea, nausea, vomiting, fatigue, decreased appetite, and anemia 鬱積範襯鑰窪獵繭網糧 (餘膚範鑰選範遞壓鬱鏇 ) 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	繭網製襯鑰構網廠製願(壓觸範選範遞餘遞蓋鹽) = 鹽醖醖鬱壓築鏇憲繭網製蓋積簾鬱淵繭構齋鏇 (淵鏇憲醖構夢鹹積鏇壓 )	积极	2020-05-25
NCT02016729 (Pubmed \| Blood Adv) 人工标引	临床1期	急性髓性白血病	36	AMG 232	鹹觸夢壓構繭餘夢願獵(獵鹽醖積製簾構襯廠廠) = Common treatment-related AEs (any grade) included nausea (58%), diarrhea (56%), vomiting (33%), and decreased appetite (25%). 淵醖蓋鬱獵膚鹹網淵鏇 (繭襯淵築廠淵範齋構構 )	积极	2019-07-09
NCT02016729 (Pubmed \| Blood Adv) 人工标引	临床1期	急性髓性白血病	36	trametinib+AMG 232		积极	2019-07-09