A Phase 1/1b Study of AOH1996 Alone or in Combination With the BCL-2 Inhibitor Venetoclax +/- Azacitidine in Patients With Relapsed/Refractory Acute Myeloid Leukemia

This phase I trial tests safety, side effects, and best dose of AOH1996 alone or in combination with venetoclax with or without azacitidine for the treatment of patients with acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or AML that has not responded to previous treatment (refractory). AOH1996 is in a class of medications called PCNA inhibitors. It inhibits cancer growth and induces deoxyribonucleic acid (DNA) damage. This may help keep cancer cells from growing and damage cancer cell DNA. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow. Giving AOH1996 alone or in combination with venetoclax with or without azacitidine may be safe, tolerable and/or effective in treating patients with AML.

开始日期2025-08-16

申办/合作机构

City of Hope National Medical Center

[+1]

ACTRN12624000738527

/ Not yet recruiting临床2期IIT

AMLM22/D4: The International AML Platform Consortium (IAPC) trial – is a randomised, 2-arm trial that will investigate the efficacy of oral Azacitidine combined with an allogeneic dendritic cell vaccine vididencel, compared with oral Azacitidine alone, in maintaining or inducing negativity for measurable residual disease (MRD) in AML patients in first complete remission (CR1) following intensive chemotherapy.

开始日期2025-06-30

申办/合作机构

The Australian Leukaemia & Lymphoma Group

[+1]

NCT06782542

/ Not yet recruiting临床2期IIT

Single-Arm Phase 2 Study of Olutasidenib, Venetoclax, and Azacitidine in IDH1 Mutated Newly Diagnosed Acute Myeloid Leukemia Patients Who Are Eligible for Intensive Induction Chemotherapy

The purpose of this study is as follows:
1. Determine whether people receiving the combination treatment of olutasidenib, venetoclax, and azacitidine have the same, more, or fewer side effects compared to the usual chemotherapy treatment that people with this condition receive.
2. Determine how well the combination treatment of olutasidenib, venetoclax, and azacitidine works compared to the usual chemotherapy treatment that people with this condition receive.

开始日期2025-04-01

申办/合作机构

University of Miami

[+1]

100 项与阿扎胞苷相关的临床结果

登录后查看更多信息

100 项与阿扎胞苷相关的转化医学

登录后查看更多信息

100 项与阿扎胞苷相关的专利（医药）

登录后查看更多信息

6,446

项与阿扎胞苷相关的文献（医药）

2025-12-01·CANCER CHEMOTHERAPY AND PHARMACOLOGY

Pharmacokinetic analysis of crushed venetoclax tablets combined with azacitizine for recurrent pediatric acute myeloid leukemia (AML)

Article

作者: Yasu, Takeo ; Yuza, Yuki ; Makimoto, Atsushi ; Matsui, Motohiro

BACKGROUND:

The efficacy of a combination therapy consisting of venetoclax (VEN) and azacytidine (AZA) for newly diagnosed acute myeloid leukemia (AML) has been confirmed in elderly patients. However, the clinical data on VEN for pediatric AML are limited. A combination therapy consisting of crushed VEN tablets and AZA (VEN/AZA) was administered to two children with recurrent AML. The pharmacokinetics of VEN were then analysed.

CASE PRESENTATION:

[Patient 1] A 1-year-old, male patient who experienced an AML relapse following an allogeneic hematopoietic stem cell transplantation received three courses of VEN/AZA. At the initial dosage of VEN (8 mg/kg), the minimum plasma concentration (C_min) was only 0.44 µg/ml, which was far less than the optimal C_min of 1.2 µg/ml. Subsequent dose-escalation to 10 mg/kg only achieved C_min 0.42 µg/ml. [Patient 2] A 3-year-old, female patient in whom infantile acute lymphoblastic leukemia was originally diagnosed experienced a recurrence in the form of AML after lineage-switching. Three courses of VEN/AZA were administered with the same therapeutic drug monitoring as in Case 1. The C_min of VEN was 0.15 µg/ml at 8 mg/kg. Afterwards, voriconazole 16 mg/kg/day was begun for a concomitant fungal infection together with VEN 2 mg/kg. This combination finally achieved C_min 1.14 µg/ml probably through CYP3A4 inhibition by voriconazole. In terms of safety, only grade 4 hematological adverse events were observed in both patients. In terms of efficacy, patient 1 and patient 2 achieved stable disease status for two months and six months, respectively.

CONCLUSION:

Pediatric patients may scarcely achieve effective plasma concentration of VEN when crushed tablets are used at the same dosage as in adults.

2025-03-01·ANALYTICAL BIOCHEMISTRY

Development and validation of a sensitive and fast bioanalytical LC-MS/MS assay for the quantitation of venetoclax and azacitidine in Rat Plasma: Application to pharmacokinetic study

Article

作者: Alsegiani, Amsha ; El-Azab, Adel ; Alsarhani, Emad ; Hefnawy, Mohamed ; Abdel-Aziz, Alaa ; Alnasser, Abdulaziz ; Attwa, Mohamed ; Alrubia, Sarah ; El-Gendy, Manal ; Jardan, Yousef Bin

The combination of venetoclax plus azacitidine (VTX-AZA) is FDA-approved to treat patients with acute myeloid leukemia (AML) aged ≥75 years and has become the standard of care for AML patients. However, the literature has not reported an analytical method for determining VTX-AZA in plasma samples. Therefore, developing an accurate and sensitive bioanalytical assay to quantify VTX-AZA in plasma is important. For the first time, this study describes the development of a new liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for the simultaneous determination of VTX and AZC in plasma samples with its application to pharmacokinetic study in rats. The assay employs repaglinide (RPG) as an internal standard. The chromatographic separations of VTX, AZC, and RPG are achieved within 2.5 min at 25 °C on an Eclipse plus C18 column (100 mm × 2.1 mm, 1.8 μm) and an isocratic mobile phase consisted of water with 0.1 % formic acid and acetonitrile (50:50, v/v, pH 3.2) at a flow rate of 0.30 mL/min. VTX and AZC have been extracted from rat plasma using the solid-phase extraction (SPE) procedure without interference from plasma endogenous. The FDA guidelines were followed in the validation of the developed assay, and linearity in rat plasma was observed for AZC and VTX, respectively, ranging from 5 to 3000 and 5-1000 ng/mL, with r ≥ 0.998. The lower limits of detection (LLOD) were 2 ng/mL for both drugs. In addition, the inter-day and intra-day accuracy were 0.8-6.6 % and 2.2-5.7 %; the inter-day and intra-day precision were 3-6.6 % and 1.5-7.1 %, respectively. The validated assay was effectively used in a pharmacokinetic investigation including the simultaneous oral administration of 40 mg/kg of AZA and 100 mg/kg of VTX to rats. The maximum plasma concentration (C_max) for AZC and VTX was 794 ± 99.6 ng/mL and 641 ± 96.9 ng/mL achieved at 0.5 ± 0.03 h and 6 ± 0.05 h, respectively. The AUC_0-∞ for AZC and VTX was 1253 ± 252.6 and 4881 ± 745.4 ng/mL.h; respectively.

2025-02-01·JOURNAL OF INFECTION AND CHEMOTHERAPY

Co-occurrence of hydatid cyst liver with acute myeloid leukaemia: A rare case report

Article

作者: Verma, Anuragani ; Singh, Anurag ; Verma, Shailendra Prasad ; Kushwaha, Rashmi ; Singh, Uma Shankar

The term "hydatid disease" refers to echinococcosis. Echinococcosis is a zoonotic disease caused by the larval stage of the Echinococcus parasite. The disease is widespread in regions where the parasite is endemic, particularly in developing nations like India. However, there are only a couple of documented case studies of echinococcosis associated with hematological malignancy in the literature. We present an extremely uncommon case of a 36-year-old male who had liver hydatidosis and was diagnosed with acute myeloid leukemia (AML)-M1. The patient received treatment for acute myeloid leukemia (daunomycin, cytarabine, and 5-azacytidine), followed by management of hydatid disease after complete remission of acute leukemia. The patient underwent periodic evaluations for one year and exhibited satisfactory improvement.

1,042

项与阿扎胞苷相关的新闻（医药）

2025-01-19

·药明康德

疾病控制率达90%的创新疗法；靶点作用率达95%的PI3Kα共价抑制剂…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 多肽偶联药物（PDC）AVA6000在治疗唾液腺癌（SGC）患者的1a期临床试验中获得积极数据，疾病控制率（DCR）达90%。 2. 蛋白降解药物BHV-1400在首个人体临床试验中获得积极结果，在最低剂量下只需一次注射，就可在4小时内将致病抗体水平降低60%。 3. PI3Kα共价抑制剂TOS-358在一项1期临床试验中对PI3Kα的靶点作用率达到95%。药明康德内容团队整理 AVA6000：公布1期临床试验数据 Avacta Therapeutics公司宣布，其在研多肽偶联药物AVA6000在治疗唾液腺癌患者的1a期临床试验中获得积极数据。唾液腺癌是一种在转移性阶段尚无标准治疗方案的疾病。AVA6000是Avacta研发管线中的首个多肽偶联药物，由阿霉素（doxorubicin）与Avacta专有的pre|CISION多肽偶联而成，该多肽可在肿瘤微环境中由成纤维细胞激活蛋白-α（FAP）特异性切割。FAP在大多数实体瘤中，与健康组织相比表达水平显著升高。Avacta的多肽偶联药物利用这一特征在肿瘤微环境中特异性释放活性药物，从而降低系统暴露和毒性，为患者提供最佳治疗效果。此次公布的数据显示，AVA6000在唾液腺癌患者中实现了显著且具有临床意义的肿瘤缩小。在接受250 mg/m²及以上剂量治疗的10名唾液腺癌患者中，DCR达90%，5名患者肿瘤显著缩小，其中包括一例部分缓解（PR，肿瘤缩小45%）和四例轻微缓解（MR，肿瘤缩小10%-19.5%）。安全性方面，在每两周一次和每三周一次两个剂量组中，AVA6000的耐受性良好，与常规剂量阿霉素相比，其血液学和心脏毒性明显降低。目前尚未在任一剂量组中确定最大耐受剂量（MTD）。 BHV-1400：公布1期临床试验的初步数据 Biohaven公司公布了其蛋白降解药物管线中的双特异性分子BHV-1400的最新结果。BHV-1400是一款基于耶鲁大学（Yale University）的MoDE技术的双特异性分子，它的一端与半乳糖缺乏型IgA1（Gd-IgA1）抗体结合，另一端与肝细胞表面的去唾液酸糖蛋白受体（ASGPR）结合。ASGPR介导肝细胞通过内吞过程，将靶点蛋白吞入细胞内进行降解。IgA肾病是由于Gd-IgA1的过度生产造成的，BHV-1400通过降低血液循环和肾脏中的Gd-IgA1水平，有望从根源治疗IgA肾病。此次公布的初步数据显示，BHV-1400在首个人体临床试验中获得积极结果，在最低剂量下只需一次注射，就可在4小时内将致病抗体水平降低60%。在某些患者中，观察到在8小时内将Gd-IgA1水平降低70%。此外，Gd-IgA1水平的降低在单次注射后可维持数天。安全性方面，迄今为止，BHV-1400在1期临床试验中的安全性和耐受性良好，未发现具有临床意义的先天和适应性免疫力的变化，并且未观察到剂量限制性毒性。这项研究将继续提高BHV-1400的剂量，探索降低Gd-IgA1水平的范围。基于该研究的积极结果，该公司还计划直接启动关键性临床试验，评估BHV-1400治疗IgA肾病的疗效和安全性。 ▲BHV-1400快速降低Gd-IgA1水平（图片来源：Biohaven公司官网） TOS-358：公布1期临床试验数据 Totus Medicines公司公布了其在研PI3Kα共价抑制剂TOS-358的1期临床试验数据。TOS-358是一款具高度特异性、强效的PI3Kα抑制剂，可在临床前模型中实现近100%的PI3Kα抑制，诱导带有PI3Kα突变的异种移植实体瘤的细胞死亡，包含结直肠癌、肺癌、乳腺癌、卵巢癌、食管癌、头颈癌，且几乎没有观察到非靶向抑制。此次公布的研究结果表明，TOS-358在低至5 mg每日两次（BID）的剂量下具有泛突变临床活性，对PI3Kα的靶点作用率达到95%，且观察到未经确认的完全缓解（CR）。安全性方面，未报道3/4级毒性。值得注意的是，几名接受给药的患者现在已超过6个月未发生进展。在成功完成1期剂量递增研究后，该公司现在启动了一项扩展研究，针对乳腺癌、子宫内膜癌、尿路上皮癌和头颈癌。 ORIC-944：公布1b期联合治疗试验数据 ORIC Pharmaceuticals公司公布了其选择性PRC2别构抑制剂ORIC-944联用阿帕鲁胺治疗转移性去势抵抗性前列腺癌（mCRPC）的1b期临床试验数据。截至2024年12月10日的数据，6例患者中有3例达到确认的PSA50应答（即PSA水平降低50%），其中2例达到确认的PSA90应答。所有PSA应答均维持≥12周，其中包括一例在38周时仍然持续的、确认的PSA90应答。 Soquelitinib：公布1期临床试验的中期数据 Corvus Pharmaceuticals公司公布了其小分子白细胞介素-2诱导的T细胞激酶（ITK）抑制剂soquelitinib用于治疗中度至重度特应性皮炎的1期临床试验的新中期数据。ITK是一种主要表达于T细胞中的酶，在T细胞和自然杀伤（NK）细胞的免疫功能中起重要作用。通过抑制ITK，soquelitinib有望抑制自身免疫和炎症反应。此次公布的结果显示，与安慰剂相比，soquelitinib治疗组在研究者总体评估（IGA）评分为0/1（皮肤症状清除或几乎清除）和湿疹面积和严重度指数较基线减少75%（EASI 75）这些临床终点方面显示出良好的疗效特征。在soquelitinib组的19例患者中，26%的患者达到IGA 0/1，37%的患者达到EASI 75。在安慰剂组的7例患者中，没有人达到IGA 0/1，也没有人达到EASI 75。安全性方面，未观察到明显的安全问题，也未发现临床上显著的实验室检测异常。 ▲治疗第28天达到终点IGA 0/1、EASI 75的患者占比（图片来源：参考资料[4]） ISM5411：公布两项1期临床试验数据英矽智能（Insilico Medicine）公司宣布，其自主研发的候选药物ISM5411已完成在澳大利亚和中国开展的两项1期研究，并取得了积极的初步结果。ISM5411是一种潜在用于治疗炎症性肠病（IBD）的小分子抑制剂，靶向PHD1/2靶点且具有新颖的分子结构，该候选药物设计和优化得到了英矽智能生成化学平台Chemistry42的支持。此次公布的结果显示，在所有剂量组中ISM5411均表现出良好的安全性和耐受性，并初步验证了肠道限制性药代动力学（PK）特征。基于1期临床试验的积极结果，英矽智能预计将于2025年下半年启动一项评估ISM5411在活动性溃疡性结肠炎患者中的2期临床试验。 MBX 1416：公布1期临床试验数据 MBX Biosciences公司公布了在健康成年受试者中开展的MBX 1416单剂量递增和多剂量递增临床试验的积极结果。MBX 1416是一种长效胰高血糖素样肽1（GLP-1）受体拮抗剂，用于治疗减肥后的低血糖症（PBH）。MBX 1416采用MBX公司新颖、专有的精准内分泌肽（PEP）平台设计，旨在防止PBH患者发生严重低血糖，使他们能够过上更健康、更独立的生活。此次公布的结果显示，MBX 1416通常安全性和耐受性良好，并且具有良好的药代动力学特征，支持每周一次给药。基于这些结果，该公司计划于2025年下半年在PBH患者中启动一项2期研究，以进一步优化剂量。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Avacta Announces Positive New Data from the AVA6000 Phase 1 trial Demonstrating Clinically Meaningful Tumor Shrinkage in Patients with Salivary Gland Cancers. Retrieved January 16, 2025, from https://www.globenewswire.com/news-release/2025/01/16/3010665/0/en/Avacta-Announces-Positive-New-Data-from-the-AVA6000-Phase-1-trial-Demonstrating-Clinically-Meaningful-Tumor-Shrinkage-in-Patients-with-Salivary-Gland-Cancers.html [2] Biohaven Highlights Portfolio Progress, Innovation, and Anticipated Milestones at the 43rd Annual J.P. Morgan Healthcare Conference; Reports Positive Degrader Data with Rapid, Deep, and Selective Lowering of Galactose-Deficient IgA1 with Next Generation Potential Therapy for IgA Nephropathy. Retrieved January 14, 2025, from https://www.prnewswire.com/news-releases/biohaven-highlights-portfolio-progress-innovation-and-anticipated-milestones-at-the-43rd-annual-jp-morgan-healthcare-conference-reports-positive-degrader-data-with-rapid-deep-and-selective-lowering-of-galactose-deficient-ig-302349336.html [3] Totus Medicines Announces Successful Completion of a Phase 1 Dose-Escalation Study and Initiation of an Expansion Trial Evaluating TOS-358, a Covalent PI3Ka Selective Therapy for the Treatment of Select Solid Tumors and Appoints Zelanna Goldberg as Chief Medical Officer. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007658/0/en/Totus-Medicines-Announces-Successful-Completion-of-a-Phase-1-Dose-Escalation-Study-and-Initiation-of-an-Expansion-Trial-Evaluating-TOS-358-a-Covalent-PI3Ka-Selective-Therapy-for-th.html [4] Corvus Pharmaceuticals Announces Data from Cohort 2 of Placebo-Controlled Phase 1 Clinical Trial of Soquelitinib for Atopic Dermatitis. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008374/0/en/Corvus-Pharmaceuticals-Announces-Data-from-Cohort-2-of-Placebo-Controlled-Phase-1-Clinical-Trial-of-Soquelitinib-for-Atopic-Dermatitis.html [5] ORIC® Pharmaceuticals Provides Early Phase 1b Combination Data for ORIC-944, Operational Highlights for 2024, and Anticipated Upcoming Milestones. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008495/0/en/ORIC-Pharmaceuticals-Provides-Early-Phase-1b-Combination-Data-for-ORIC-944-Operational-Highlights-for-2024-and-Anticipated-Upcoming-Milestones.html [6] 英矽智能公布炎症性肠病药物ISM5411两项I期临床试验的积极结果. Retrieved January 17, 2025, from https://www.prnasia.com/story/474986-1.shtml [7] MBX Biosciences Announces Positive Phase 1 Topline Results for MBX 1416 for the Treatment of Post-bariatric Hypoglycemia. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/07/3005223/0/en/MBX-Biosciences-Announces-Positive-Phase-1-Topline-Results-for-MBX-1416-for-the-Treatment-of-Post-bariatric-Hypoglycemia.html [8] Mersana Therapeutics Announces Positive Initial Clinical Data from Phase 1 Clinical Trial of Emiltatug Ledadotin (XMT-1660); Initiation of Expansion in Triple Negative Breast Cancer. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007493/0/en/Mersana-Therapeutics-Announces-Positive-Initial-Clinical-Data-from-Phase-1-Clinical-Trial-of-Emiltatug-Ledadotin-XMT-1660-Initiation-of-Expansion-in-Triple-Negative-Breast-Cancer.html [9] Axcynsis Therapeutics Receives FDA Clearance for IND Application of AT03-65, a Differentiated CLDN6-Targeting ADC, Powered by AxcynDOT™ Technology. Retrieved January 17, 2025, from https://www.prnewswire.com/news-releases/axcynsis-therapeutics-receives-fda-clearance-for-ind-application-of-at03-65-a-differentiated-cldn6-targeting-adc-powered-by-axcyndot-technology-302350114.html [10] Ocugen, Inc. Announces Positive 2-Year Data Across Multiple Mutations from Phase 1/2 Clinical Trial of OCU400 —A Novel Modifier Gene Therapy for Retinitis Pigmentosa. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008252/0/en/Ocugen-Inc-Announces-Positive-2-Year-Data-Across-Multiple-Mutations-from-Phase-1-2-Clinical-Trial-of-OCU400-A-Novel-Modifier-Gene-Therapy-for-Retinitis-Pigmentosa.html [11] Verismo Therapeutics Announces First Patient Infused in Phase 1 CELESTIAL-301 Clinical Trial of SynKIR™-310. Retrieved January 17, 2025, from https://www.prnewswire.com/news-releases/verismo-therapeutics-announces-first-patient-infused-in-phase-1-celestial-301-clinical-trial-of-synkir-310-302347464.html [12] Caribou Biosciences Initiates the CB-010 GALLOP Phase 1 Trial in Lupus and Provides Outlook for Multiple Clinical Datasets in 2025. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008079/0/en/Caribou-Biosciences-Initiates-the-CB-010-GALLOP-Phase-1-Trial-in-Lupus-and-Provides-Outlook-for-Multiple-Clinical-Datasets-in-2025.html [13] Arcturus Therapeutics Announces Initiation of Phase 1 H5N1 Flu Vaccine Trial. Retrieved January 17, 2025, from https://ir.arcturusrx.com/news-releases/news-release-details/arcturus-therapeutics-announces-initiation-phase-1-h5n1-flu [14] Korro Bio Announces Dosing of First Participants in REWRITE Phase 1/2a Study of KRRO-110 for Alpha-1 Antitrypsin Deficiency and Provides Pipeline Update. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008445/0/en/Korro-Bio-Announces-Dosing-of-First-Participants-in-REWRITE-Phase-1-2a-Study-of-KRRO-110-for-Alpha-1-Antitrypsin-Deficiency-and-Provides-Pipeline-Update.html [15] NextCure Announces First Patient Dosed in the Phase 1 Study of LNCB74 (B7-H4 ADC) as Therapeutic for Treating Multiple Cancers. Retrieved January 17, 2025, from https://ir.nextcure.com/news-releases/news-release-details/nextcure-announces-first-patient-dosed-phase-1-study-lncb74-b7 [16] LAVA Doses First Patient in Phase 1 LAVA-1266 Study in Hematological Cancers. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007674/0/en/LAVA-Doses-First-Patient-in-Phase-1-LAVA-1266-Study-in-Hematological-Cancers.html [17] Context Therapeutics Announces First Patient Dosed in the Phase 1 Clinical Trial of CTIM-76. Retrieved January 17, 2025, from https://www.globenewswire.com/de/news-release/2025/01/14/3009673/0/en/Context-Therapeutics-Announces-First-Patient-Dosed-in-the-Phase-1-Clinical-Trial-of-CTIM-76.html [18] Ocugen, Inc. Announces First Patient Dosed in Phase 1 Clinical Trial of OCU200—a Novel Integrin-Targeting Biologic for Diabetic Macular Edema. Retrieved January 17, 2025, from https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-first-patient-dosed-phase-1-clinical-trial [19] ProMIS Neurosciences Initiates Phase 1b Clinical Trial (PRECISE-AD) in Alzheimer’s Disease. Retrieved January 17, 2025, from https://www.promisneurosciences.com/news-media/press-releases/detail/236/promis-neurosciences-initiates-phase-1b-clinical-trial [20] Aptose Announces First AML Patients Dosed with Tuspetinib Triplet Frontline Therapy in TUSCANY Trial. Retrieved January 17, 2025, from https://www.aptose.com/news-media/press-releases/detail/307/aptose-announces-first-aml-patients-dosed-with-tuspetinib [21] ORYZON announces first patient dosed in NCI-sponsored iadademstat in combination with venetoclax and azacitidine clinical trial in first line acute myeloid leukemia. Retrieved January 17, 2025, from https://www.oryzon.com/en/news-events/news/oryzon-announces-first-patient-dosed-nci-sponsored-iadademstat-combination [22] 한미약품-GC녹십자, ‘파브리병’ 국내 1/2상 IND 승인. Retrieved January 17, 2025, from https://www.biospectator.com/news/view/24043 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床结果临床1期多肽偶联药物

2025-01-16

·小药说药

肿瘤免疫中的表观遗传调控

关注小药说药，一起成长！前言遗传和表观遗传变化都是癌症发生、肿瘤进展和转移的重要因素。从广义上讲，癌症的发病率与生物/遗传年龄直接相关。DNA甲基化是一种重要的表观遗传调控机制，在生命周期中不断变化，是“表观遗传衰老”过程的重要组成部分。值得注意的是，最近的研究已经证实表观遗传衰老在肿瘤发生中起主要作用。表观遗传学改变通过影响广泛组织学中的多种致癌基因与抑癌基因途径，以及通过影响免疫细胞（如T细胞和NK细胞）的激活、分化和功能从而促进癌症的发生。事实上，最近的一项研究表明，正是组织环境诱导的表观遗传编程启动了肿瘤发生，这些发现为表观遗传药物的应用提供了强有力的理论基础，不仅可以作为癌症治疗药物，还可以用于预防癌症，因为它们可以协同靶向“正常”细胞，包括免疫细胞和癌前细胞。基于表观遗传学的治疗旨在调节影响免疫细胞、其他正常细胞和/或癌细胞中各种信号通路的转录编程，从而影响这些细胞群体的命运。表观遗传药物是作用于细胞表观基因组以发挥其功能的化学物质，这些药物包括DNA甲基转移酶（DNMT）、DNA去甲基酶、组蛋白去乙酰化酶（HDAC）、组蛋白乙酰转移酶（HATs）、组蛋白甲基转移酶（HMT）、组蛋白去甲基酶（HDMs）和其他相关酶的抑制剂。此外，microRNA（miRNA）和长非编码RNA（lncRNAs）也是多种关键生物过程的重要表观遗传介质，包括致癌和免疫反应，这是有效癌症治疗的两个关键靶点。表观遗传途径 DNA甲基化 DNA甲基化作为一种主要的表观遗传学标记，可通过有丝分裂遗传，并参与稳定基因转录抑制，尤其是当其位于哺乳动物基因转录起始点附近时。研究的最深入的DNA共价修饰是5-甲基胞嘧啶（5mC），这是一种由DNMT催化的标记。在哺乳动物基因组中，5mC主要存在于CpG二核苷酸中，人类基因组中2800万CpG二核苷酸中70–80%的CpG被甲基化。在哺乳动物中，发现了三种活跃的DNMT，分别命名为DNMT1、DNMT3a和DNMT3b。组蛋白乙酰化组蛋白可以经历多种形式的翻译后修饰（PTMs），包括乙酰化、甲基化、磷酸化、泛素化以及ADP核糖基化、磺酰化和瓜氨酸化。这些组成所谓的“组蛋白密码”，调节染色质结构、重塑酶的募集和基因活动的调节。组蛋白赖氨酸残基的乙酰化影响基因组的组织和功能。组蛋白H3和H4的乙酰化由两组酶决定：HATs和组HDAC。这两组酶决定组蛋白的乙酰化状态，并以可逆方式工作。在人类中，有18种HDAC酶分为四类：Rpd3样蛋白的I类（HDAC1、HDAC2、HDAC3和HDAC8）；类Hda1蛋白的II类（HDAC4、HDAC5、HDAC6、HDAC7、HDAC9和HDAC10）；Sir2样蛋白的III类（SIRT1、SIRT2、SIRT3、SIRT4、SIRT5、SIRT6和SIRT7）和第四类蛋白质（HDAC11）。这些酶及其在癌症中的功能已被广泛研究。组蛋白甲基化组蛋白甲基化是表观遗传修饰的第三种主要类型。为了完成这一可逆过程，涉及两大类催化甲基加成的酶：蛋白质精氨酸甲基转移酶（PRMT）和组蛋白赖氨酸甲基转移酶（HKMT）。癌症环境中的关键赖氨酸和精氨酸甲基转移酶包括zeste同源物2（EZH2）、G9a、DOT1L以及PRMTs 1和5。另一组称为组蛋白去甲基酶的酶逆转这一过程。组蛋白磷酸化磷酸化是另一种高度动态的组蛋白PTM形式。它发生在丝氨酸、苏氨酸和酪氨酸残基上，主要发生在组蛋白N端尾部，受激酶和磷酸酶的竞争作用控制。作为“组蛋白代码”的重要组成部分，PTM在DNA损伤修复、染色质致密化、转录调控以及包括肿瘤发生和癌症进展在内的一系列生物学过程中起着关键作用。肿瘤微环境的表观遗传调节肿瘤微环境（TME）由多种细胞类型组成。除肿瘤细胞外，TME还包含多种非上皮细胞类型，包括构成血管系统的细胞（内皮细胞、周细胞和平滑肌细胞）、参与免疫监测的细胞（淋巴细胞、巨噬细胞和肥大细胞）以及基质细胞（即成纤维细胞），这些细胞在细胞外基质（ECM）中，分泌一系列可扩散生长因子、细胞因子和趋化因子。人们早就认识到，癌症发生促进以促血管生成生长因子表达、ECM表达改变、成纤维细胞增殖加速和炎性细胞浸润增加为特征的基质变化。 TME的表观遗传改变控制着组织缺氧状态，并在细胞对缺氧的反应和癌细胞代谢中起着关键作用。表观遗传调控因子可与缺氧诱导转录因子（HIF）家族基因协同工作，在HIF依赖性启动后很长时间内维持缺氧适应的细胞表型。表观遗传变化稳定HIF与其转录靶点的结合，从而影响直接HIF反式激活后的组蛋白去甲基化酶活性，并最终导致缺氧TME中组蛋白修饰和DNA甲基化的整体模式，JMJD1A表达的低氧上调作为信号放大器促进低氧基因表达，最终促进肿瘤生长。巨噬细胞是TME中的关键固有免疫细胞，它们在TME中调节原发性肿瘤生长、血管生成、转移扩散和肿瘤对介入治疗的反应。在巨噬细胞中，缺氧减弱了Jumonji组蛋白去甲基化酶活性的表达，导致组蛋白H3K9甲基化增加和趋化因子表达降低，从而导致TME内免疫景观的变化。免疫细胞的表观遗传调节表观遗传机制在免疫细胞分化和功能中发挥关键作用，确保在不同组织微环境条件下免疫细胞中恰当的基因表达模式。重要的是，表观遗传机制在TME内的免疫细胞和基质细胞类型中起着决定性作用。固有免疫细胞（髓系细胞和NK细胞）髓系细胞在适应性免疫系统识别癌细胞中发挥重要作用，并协调炎症和保护性抗肿瘤免疫反应的启动。这些细胞包括粒细胞、单核细胞、巨噬细胞、中性粒细胞、DC和MDSC。 DC细胞启动并协调针对感染和疾病的适应性免疫反应，它们是免疫记忆和免疫耐受发展的核心。树突状细胞迅速整合来自其组织微环境的信号，并相应地对这些信号作出反应，这种动态变化依赖于DC细胞染色质结构的表观遗传变化。在巨噬细胞中，其功能极化状态需要对靶基因表达进行精确的时间和情境调节。在M1和M2极化期间，表观遗传变化在改变细胞信号和特征基因图谱中发挥作用。 MDSCs在肿瘤形成过程中被诱导，它们介导有效的肿瘤促进活动。研究表明，在肿瘤相关培养基存在的情况下，MDSCs的基因组中存在广泛的去甲基化和某些特殊位点的DNA甲基化，这些和免疫抑制特征的特异性基因增加有关。此外，许多研究表明，组蛋白修饰的表观遗传途径调节MDSCs的各个方面。例如，HDAC11是一种新的表观遗传调节因子，在肿瘤相关的MDSC中调节细胞的扩增和功能。 NK细胞在免疫监视和消除应激、感染或转化细胞方面发挥着重要作用。对于NK细胞，H3K4me3去甲基化酶Kdm5a是细胞激活所必需的。此外，慢性刺激的NK细胞在被肿瘤靶点重新激发时表现出功能紊乱，这些无能的NK细胞表现出特定的表观遗传重编程模式，DNA甲基化发生全基因组改变。 CD4+T细胞表观遗传学机制在Th1和Th2细胞的细胞分化和功能中起着关键作用。STAT4和STAT6转录因子在辅助性T细胞分化过程中的表观遗传修饰和转录调节中起着调控作用。研究发现，STAT4在促进活跃的表观遗传标记方面具有更为显著的作用，而STAT6在对抗抑制性标记方面具有更为显著的作用。对于T滤泡辅助细胞（Tfh）细胞，已经证明VHL-HIF-1α轴在通过糖酵解表观遗传重编程启动Tfh细胞发育过程中起着重要作用。EZH2是一种HMT，催化H3K27me3并主要通过HMT活性影响Th1、Th2和Treg细胞。研究表明，EZH2敲除会损害Tfh分化和转录编程的激活。 Treg细胞 Treg细胞的发育严重依赖于FoxP3，FoxP3的表达是最佳Treg抑制活性所必需的，过去几十年的研究表明，增强子区CpG岛的DNA甲基化控制着T细胞中FoxP3的表达。此外，TET-甲基胞嘧啶双加氧酶对Treg细胞的功能稳定性也至关重要。一系列研究证明了TET在维持Treg细胞中稳定的FoxP3表达中的关键作用。 EZH2在Treg细胞中的重要性也得到了证实。EZH2对Treg的分化和T效应细胞的扩张都至关重要，通过遗传或药理学手段破坏Treg细胞中的EZH2活性，导致肿瘤浸润性Treg细胞获得促炎功能，重塑TME，增强CD8+和CD4+效应T细胞的募集和功能，从而消除肿瘤。 CD8+T细胞基因表达的表观遗传调控在获得和维持CD8+T细胞的效应器功能，以及记忆性CD8+T细胞对抗原再激发的快速而稳健的反应中起着关键作用。表观遗传机制也影响CD8+T细胞的干性及其命运。组蛋白乙酰化通过效应分子的差异表达促进CD8+T细胞快速而稳健的记忆反应。与原始CD8+T细胞相比，记忆CD8+T细胞中效应基因H3赖氨酸9乙酰化（H3K9Ac）显著提高。此外，HDAC3已被确定为CD8+T细胞效应器分化和细胞毒性潜能的表观遗传调节因子。肿瘤细胞和免疫分子的表观遗传调节癌细胞的代谢重编程是公认的癌症标志，这已成为调节抗肿瘤免疫反应的关键免疫抑制机制。代谢重编程和表观遗传重编程是相互关联的，并且在很大程度上，代谢状态决定了癌症的表观遗传学。糖酵解或氧化磷酸化等代谢途径在炎症和组织修复过程中调节巨噬细胞功能，α-酮戊二酸通过代谢和表观遗传重编程协调巨噬细胞活化至M2表型。糖酵解增强也被确定影响骨桥蛋白基因表达的表观遗传修饰。最终，TME内的代谢条件加强了癌细胞和免疫细胞的表观遗传重编程，导致免疫抑制性微环境，然而，这些表观遗传修饰表现出可通过表观遗传调节剂纠正的可塑性。在分子水平上，已知与免疫功能（STING）、CD8+细胞毒性T细胞（GzmB、IFN-γ、IL-2、IL-12）和FOXP3+Treg细胞相关的关键效应分子通过表观遗传途径进行调节。事实上，许多细胞因子和趋化因子在癌症中通过表观遗传途径调节。免疫检查点分子（ICMs）包括程PD-1、CTLA-4、TIM-3、LAG-3以及TIGIT。这些分子及其受体在癌细胞和免疫细胞表面的表达，或其可溶性分泌形式，可帮助肿瘤细胞逃避免疫监视。表观遗传机制在调节TME中ICMs及其受体的表达中起着关键作用。作为一个具体的例子，LAG-3 DNA甲基化与肿瘤和免疫细胞中该免疫检查点分子的表达相关，影响透明细胞肾细胞癌中免疫细胞浸润的命运。表观遗传靶向药物表观遗传药物经常与其他免疫刺激剂联合使用，以实现五个目标：1）癌细胞生长停滞；2）诱导肿瘤细胞死亡（通过凋亡、坏死、自噬）；3）促进肿瘤相关新抗原的表达以提高免疫细胞识别能力；4.）缺氧逆转和肿瘤血管生成抑制；以及5）TME中免疫细胞（DC、T细胞等）功能的调节。目前，大量涉及表观遗传调控途径的小分子酶抑制剂或激活剂正被开发用于临床。许多表观遗传药物已获得监管机构批准用于治疗人类恶性肿瘤。 2004年，FDA批准5-azaC（商品名Vidaza）用于骨髓增生异常综合征（MDS）的所有五个阶段，随后于2006年批准了5-aza-dC。这两种药物目前代表了干细胞疗法不适用时MDS的一线疗法。它们也被应用于慢性粒单核细胞白血病（CMML）和AML的治疗。一些HDAC抑制剂（HDACi）也已获得FDA批准用于临床。Vorinostat和romidepsin是这类药物中最早被批准用于治疗皮肤T细胞淋巴瘤（CTCL）的药物。SAHA，也称为Zolinza或Vorinostat，于2006年获得FDA批准，目前是CTCL患者的第三线治疗选择。Romidepsin是2009年FDA批准的第二种HDAC抑制剂。随后，Belinostat和Panobinostat以及Chidamine均被批准用于治疗复发或难治性外周T细胞淋巴瘤（PTCL）或多发性骨髓瘤。 FDA药品批准的第三波浪潮发生在过去几年中。2017年和2018年，异柠檬酸脱氢酶1和2（IDH1/2）抑制剂Enasidenib和Ivosidenib分别被批准用于治疗复发或难治性AML。最后，在2020年，FDA加速批准了tazemetostat，一种EZH2的抑制剂，用于治疗上皮样肉瘤和复发/难治性滤泡性淋巴瘤。表观遗传药物的临床前景到目前为止，除了少数类型的实体瘤、T细胞淋巴瘤、上皮样肉瘤和难治性滤泡性淋巴瘤外，表观遗传学药物在晚期肿瘤中通常无法证明足够的疗效，从而无法获得FDA或其他监管机构的批准。然而，一些关于实体瘤的临床研究显现出有希望的前景。首先，Tazemetostat是第一类抑制剂的代表，对两种实体瘤有效。单药治疗显示出有临床意义的、持久的反应，并且在经多次治疗的复发性或难治性滤泡性淋巴瘤患者或晚期上皮样肉瘤患者中普遍具有良好的耐受性。其次，两种或两种以上的表观遗传药物的组合可能是提高治疗抗肿瘤疗效的一个很好的选择。在一项研究中，证明了azacitidine和romidepsin与IFN-α的联合具有很高的治疗潜力，其靶向的是结直肠癌最具侵袭性的细胞成分（即转移细胞和癌干细胞），并调节关键的生存和死亡途径（包括肿瘤ICD）。在另一项研究中，研究人员评估了使用azacitidine和entinostat对复发性转移性非小细胞肺癌患者的联合治疗，在一些难治性NSCLC患者中显示出客观、持久的反应。此外，在临床前研究中，已报道EZH2抑制剂可增强ICIs的抗肿瘤反应。在一个病例报告中，一名使用EZH2抑制剂（tazemetostat）治疗的SMARCB1阴性脊索瘤患者对放疗的持续全身反应超过2年。功能分析显示，CD8+ T细胞和Treg细胞的肿瘤内和间质浸润显著增加，与T细胞上PD-1和LAG-3检查点分子的表达增强有关。这些结果表明EZH2抑制促进持续的抗肿瘤免疫反应，导致免疫检查点激活。新出现的临床数据也表明，表观遗传药物和ICIs的联合疗法有望用于一系列实体癌患者。目前，有多项表观遗传药物和ICIs联合治疗的临床试验正在进行中。小结令人信服的证据表明，表观遗传调控影响癌细胞、免疫细胞、基质细胞、癌细胞和免疫细胞之间的相互作用以及免疫TME的状态。因此，作为一种干预手段，表观遗传调节本身可以诱导强大的抗肿瘤免疫。因此，进一步增强免疫治疗效果的一个合理策略是将某些表观遗传调节因子与一种或多种经典免疫治疗方案相结合，如癌症疫苗、ICIs、溶瘤病毒、CAR-T细胞、TCR-T细胞或其他新型免疫刺激剂。表观遗传药物可以诱导ICD并使肿瘤由冷变热，它们可能与其他免疫治疗方案产生协同作用。未来，这些联合治疗方案可能在临床研究中显示出良好的应用前景。参考文献： 1.Epigenetic modulation of antitumor immunityfor improved cancer immunotherapy. Mol Cancer. 2021; 20: 171. 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。

寡核苷酸核酸药物

2025-01-15

·access wire

Aptevo\'s Peter Pavlik, PhD, Chairing Session on \"Bi and Multispecific Biologics\" at Cambridge Healthcare Institute\'s Pep Talk 2025

Also giving an in-session talk titled \"Modular Multispecific Biotherapeutics: Rapid Therapeutic Design with the ADAPTIR® Platform,\" showcasing Aptevo\'s drug engineering and rational drug design expertise SEATTLE, WA / ACCESSWIRE / January 15, 2025 / Aptevo Therapeutics (\"Aptevo\") (NASDAQ:APVO) today announced that Peter Pavlik, PhD, Senior Director of Protein Engineering, will chair a session titled \"Bi and Multispecific Biologics\" and present a talk,\"Modular Multispecific Biotherapeutics: Rapid Therapeutic Design with the ADAPTIR® Platform,\" at the Cambridge Healthcare Institute\'s Pep Talk conference today.DetailsSession Title: Bi and Multispecific BiologicsTalk Title: Modular Multispecific Biotherapeutics: Rapid Therapeutic Design with the ADAPTIR™ Platform (talk being given as part of this session)Session Chair and Talk Presenter: Peter Pavlik, PhDDate/Time: Wednesday, January 15th from 3:15-5:20 US Pacific time.About Dr. PavlikPeter Pavlik, PhD, serves as the Senior Director of Protein Engineering at Aptevo Therapeutics. In his career at Aptevo and previously MedImmune/AstraZeneca and Los Alamos National Labs, he has implemented novel technologies to streamline discovery of binding domains and their incorporation into stable and efficacious biotherapeutics. Dr. Pavlik has oversight over all processes currently used at Aptevo, which are optimized to multiple areas of drug development from target validation to antibody discovery to IND and to clinic. Dr. Pavlik has a unique understanding of the biopharma industry from the large and small company perspectives.About Aptevo TherapeuticsAptevo Therapeutics Inc. (NASDAQ:APVO) is a clinical-stage biotechnology company focused on developing novel bispecific immunotherapies for the treatment of cancer. The company has two clinical candidates. Mipletamig is currently being evaluated in RAINIER, a Phase 1b/2 trial for the treatment of frontline acute myeloid leukemia in combination with standard of care venetoclax + azacitidine. Mipletamig has orphan status for AML according to the Orphan Drug Act. ALG.APV-527, a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4, is being co-developed with Alligator Bioscience and is being evaluated in a Phase 1 clinical trial for the treatment of multiple solid tumor types likely to express 5T4. The Company has three pre-clinical candidates with different mechanisms of action designed to target a range of solid tumors. All pipeline candidates were created from two proprietary platforms, ADAPTIR® and ADAPTIR-FLEX®. The Aptevo mission is to improve treatment outcomes and transform the lives of cancer patients. For more information, please visit www.aptevotherapeutics.com.Safe Harbor StatementThis press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, including, without limitation, Aptevo\'s expectations regarding the effectiveness of its ADAPTIR® and ADAPTIR-FLEX® platform technologies and whether such technologies will accelerate drug discovery and development, statements related to the performance of Aptevo\'s drug candidates in the clinic and whether such performance will translate into improved patient outcomes, statements related to the progress of and enthusiasm for Aptevo\'s preclinical and clinical programs, statements related to Aptevo\'s ability to generate stockholder value, whether Aptevo will continue to have momentum in its business in the future, and any other statements containing the words \"may,\" \"believes,\" \"expects,\" \"potential,\" \"designed,\" \"engineered,\" \"innovative,\" \"initiate,\" \"allow,\" \"promise,\" \"plans,\" \"will\" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based on Aptevo\'s current intentions, beliefs, and expectations regarding future events. Aptevo cannot guarantee that any forward-looking statement will be accurate. Investors should realize that if underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could differ materially from Aptevo\'s expectations. Investors are, therefore, cautioned not to place undue reliance on any forward-looking statement.There are several important factors that could cause Aptevo\'s actual results to differ materially from those indicated by such forward-looking statements, including a deterioration in Aptevo\'s business or prospects; further assessment of preliminary or interim data or different results from later clinical trials; adverse events and unanticipated problems, adverse developments in clinical development, including unexpected safety issues observed during a clinical trial; adverse developments in the U.S. or global capital markets, credit markets or economies generally; and changes in regulatory, social, macroeconomic, and political conditions. For instance, actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the uncertainties inherent in the initiation, enrollment and maintenance of patients in clinical trials, uncertainties inherent in the results of preliminary or interim data and preclinical and clinical studies being predictive of the results of later-stage clinical trials, the availability and timing of data from ongoing clinical trials, the trial design includes combination therapies that may make it difficult to accurately ascertain the benefits of mipletamig, expectations for the timing and steps required in the regulatory review process, expectations for regulatory approvals, the impact of competitive products, our ability to enter into agreements with strategic partners or raise funds on acceptable terms or at all and other matters that could affect the availability or commercial potential of the Company\'s product candidates, business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises such as the novel coronavirus (referred to as COVID-19), geopolitical risks, including the current war between Russia and Ukraine as well as the war between Israel and Hamas, and macroeconomic conditions such as rising inflation and interests rates, increased market volatility and decreased consumer confidence. These risks are not exhaustive, Aptevo faces known and unknown risks. Additional risks and factors that may affect results are set forth in Aptevo\'s filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2023, and its subsequent reports on Form 10-Q and current reports on Form 8-K. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Aptevo\'s expectations in any forward-looking statement. Any forward-looking statement speaks only as of the date of this press release, and, except as required by law, Aptevo does not assume any obligation to update any forward-looking statement to reflect new information, events, or circumstances.Aptevo TherapeuticsMiriam Weber MillerEmail: [email protected] or [email protected]Phone: 206-859-6629SOURCE: Aptevo TherapeuticsRelated Documents:

免疫疗法临床1期孤儿药

100 项与阿扎胞苷相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D03021	阿扎胞苷	L01BC07	DB00928

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
幼年型骨髓单核细胞白血病	美国	Bristol Myers Squibb Co.	2022-05-20
骨髓增生性疾病	欧盟	betapharm Arzneimittel GmbH	2020-03-24
骨髓增生性疾病	冰岛	betapharm Arzneimittel GmbH	2020-03-24
骨髓增生性疾病	列支敦士登	betapharm Arzneimittel GmbH	2020-03-24
骨髓增生性疾病	挪威	betapharm Arzneimittel GmbH	2020-03-24
费城染色体阳性慢性粒细胞白血病	中国	Bristol-Myers Squibb Pharma EEIG	2017-04-24
高危骨髓增生异常综合征	澳大利亚	Celgene Pty Ltd.	2009-11-30
急性髓性白血病	欧盟	Bristol-Myers Squibb Pharma EEIG	2008-12-17
急性髓性白血病	冰岛	Bristol-Myers Squibb Pharma EEIG	2008-12-17
急性髓性白血病	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2008-12-17
急性髓性白血病	挪威	Bristol-Myers Squibb Pharma EEIG	2008-12-17
慢性粒单核细胞白血病	欧盟	Bristol-Myers Squibb Pharma EEIG	2008-12-17
慢性粒单核细胞白血病	冰岛	Bristol-Myers Squibb Pharma EEIG	2008-12-17
慢性粒单核细胞白血病	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2008-12-17
慢性粒单核细胞白血病	挪威	Bristol-Myers Squibb Pharma EEIG	2008-12-17
骨髓增生异常综合征	美国	Bristol Myers Squibb Co.	2004-05-19

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
免疫母细胞性淋巴结病	临床3期	日本	Celgene Corp.	2018-11-06
血小板减少症	临床3期	美国	Celgene Corp.	2013-04-26
血小板减少症	临床3期	澳大利亚	Celgene Corp.	2013-04-26
血小板减少症	临床3期	比利时	Celgene Corp.	2013-04-26
血小板减少症	临床3期	巴西	Celgene Corp.	2013-04-26
血小板减少症	临床3期	加拿大	Celgene Corp.	2013-04-26
血小板减少症	临床3期	捷克	Celgene Corp.	2013-04-26
血小板减少症	临床3期	丹麦	Celgene Corp.	2013-04-26
血小板减少症	临床3期	芬兰	Celgene Corp.	2013-04-26
血小板减少症	临床3期	法国	Celgene Corp.	2013-04-26

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASH2024	N/A	急性髓性白血病	-	Azacitidine + Venetoclax	餘夢繭衊鑰鑰艱憲艱壓(選糧遞繭廠糧鏇淵鹽繭) = 窪遞鹹鹹壓醖鹹膚膚積鏇窪遞築憲壓製積鹽襯 (夢願膚鏇網鏇獵艱淵鏇 ) 更多	-	2024-12-09
ASH2024	N/A	骨髓增生异常综合征	-	Azacitidine + Durvalumab	範簾壓膚蓋獵壓鑰積醖(積蓋淵窪鹽願夢鬱廠襯) = 廠願淵顧觸構鹹齋蓋壓夢膚鑰構製簾窪壓鬱壓 (醖艱窪艱網鹹鬱構獵糧 ) 更多	-	2024-12-09
				Azacitidine	範簾壓膚蓋獵壓鑰積醖(積蓋淵窪鹽願夢鬱廠襯) = 憲鏇觸蓋積鹽憲顧遞築夢膚鑰構製簾窪壓鬱壓 (醖艱窪艱網鹹鬱構獵糧 ) 更多
735 (ASH2024)	临床1/2期	急性髓性白血病 TP53mutation	110	Magrolimab (Magro) + Azacitidine (AZA) + Venetoclax (VEN)	範膚積網糧淵鏇願艱淵(齋壓膚壓鏇齋願壓構鹹) = 遞獵積襯壓蓋壓顧鹽廠廠遞繭憲簾窪齋壓觸窪 (襯齋鑰顧齋憲襯齋鑰鏇, 7 ~ 13) 更多	积极	2024-12-09
ASH2024	临床3期	急性髓性白血病	70	Azacitidine+HAG regime	鏇夢網觸顧窪淵顧鏇齋(網鏇窪鏇膚選顧餘網醖) = 醖鏇遞網製構醖鑰網網選積積壓淵齋憲遞壓夢 (網鑰範壓願憲鬱鹽繭鹹 ) 更多	积极	2024-12-09
ASH2024	N/A	复发性急性髓细胞白血病	-	Venetoclax	鏇構構選齋構糧廠願齋(鏇衊觸窪遞餘憲壓構廠) = 獵糧廠齋願餘製膚夢鹽鬱製憲構壓遞鹽築膚壓 (顧蓋鑰製積糧鑰膚衊鹽, 6.2 ~ 16.0)	-	2024-12-09
NCT03013998 (BAMT, ASH2024)	临床1/2期	急性髓性白血病	1,096	Non-Intensive (Off-Protocol)	繭鏇窪築鹽顧膚鏇積蓋(觸齋艱衊鹹艱壓遞淵鹹) = 鏇鏇範衊鹹遞憲鏇製積鏇夢壓構鏇醖獵窪淵襯 (鹽衊鏇範製齋衊觸選築, 6.9 ~ 13.4) 更多	积极	2024-12-09
				Ven/HMA (Off-Protocol)	繭鏇窪築鹽顧膚鏇積蓋(觸齋艱衊鹹艱壓遞淵鹹) = 鏇獵淵廠糧鏇鹽壓醖築鏇夢壓構鏇醖獵窪淵襯 (鹽衊鏇範製齋衊觸選築, 2.2 ~ 10.7) 更多
NCT04550442 (ASH2024) 人工标引	临床1/2期	高危骨髓增生异常综合征 \| 慢性粒单核细胞白血病	33	AzacitidineVenetoclax	夢築觸遞鏇鏇鹽醖範網(鑰艱艱憲鏇夢齋艱醖膚) = 餘衊積餘簾鏇艱糧鑰鹽衊鏇襯鏇襯夢醖憲遞獵 (淵鏇築膚糧顧觸願衊鬱 ) 更多	积极	2024-12-08
				Azacitidine and Venetoclax (TP53 mutation)	構淵衊鏇鏇選廠繭襯壓(鹽構鹹顧鹹膚構觸蓋醖) = 蓋襯網衊選製構選齋糧築夢簾積淵遞鑰淵鹽蓋 (夢獵窪憲顧齋製襯鏇選, 0.9 ~ 5)
NCT04501120 (APG2575AC101, ASH2024) 人工标引	临床1/2期	骨髓增生异常综合征	49	Lisaftoclax Azacitidineazacitidine (R/R MDS)	鑰鹽蓋艱繭觸簾憲鑰憲(願壓簾鏇獵夢遞淵夢壓) = 觸遞鏇蓋顧簾築積鹹糧鬱醖築製齋鹹網淵築衊 (憲醖醖齋憲繭簾築膚淵 ) 更多	积极	2024-12-08
				Lisaftoclax Azacitidineazacitidine (TN MDS)	鬱襯齋壓築憲衊簾範觸 \| 鑰鹽蓋艱繭觸簾憲鑰憲(構構衊廠糧廠夢鏇顧構) = 憲繭醖襯鏇憲選獵淵襯餘鏇夢構壓壓鏇糧遞積 (積鬱夢窪構獵襯淵積觸, 61.5 ~ 89.2) 更多
NCT02719574 (ASH2024) 人工标引	临床1/2期	IDH1突变急性髓性白血病 IDH1 Mutation	67	Olutasidenib 150 mg + azacitidine	淵獵築遞範夢鏇膚艱獵(襯遞鹹鏇願製醖淵鏇醖) = 繭淵鏇夢醖觸糧鏇範簾觸鬱鹽齋網鹽繭獵醖艱 (襯壓簾膚衊製鏇網繭顧, 21 ~ 44) 更多	积极	2024-12-08
				Olutasidenib 150 mg + azacitidine (prior OLU exposure)	淵獵築遞範夢鏇膚艱獵(襯遞鹹鏇願製醖淵鏇醖) = 鏇構選簾齋選衊製鏇夢觸鬱鹽齋網鹽繭獵醖艱 (襯壓簾膚衊製鏇網繭顧, 24 ~ 52) 更多
ASH2024	N/A	骨髓增生性疾病	-	Azacitidine alone	構築糧鏇淵鏇淵醖觸鏇(壓鹽餘網鬱襯廠製餘淵) = 觸鹽簾壓鹹遞壓選簾艱蓋選膚餘憲鏇鑰鹹蓋齋 (鏇願範築鹹齋艱顧窪艱, 0.50 ~ 1.08) 更多	-	2024-12-08
				Azacitidine in combination	憲簾艱廠襯觸襯構衊獵(艱鏇餘網遞衊鑰窪獵鹽) = 築構鏇觸憲範鏇膚艱觸簾夢獵窪築築選餘鹽衊 (餘鑰簾願壓願觸糧艱積 ) 更多