A Multicenter, Single-arm Clinical Study of Venetoclax and Ivosidenib Combined With Intensive Chemotherapy in the Treatment of Fit Adult Acute Myeloid Leukemia Patients With IDH1 Mutations

Leukemia is one of the common malignant tumors threatening human health. Intensive chemotherapy or non-intensive chemotherapy has limited efficacy. There is an urgent need to improve treatment outcomes with more specific, well-designed drugs that target leukemia specifically.
The induction therapy of venetoclax combined with demethylation agents (HAM) significantly improves the response rate in elderly unfit AML patients (more than 60%), and studies are being conducted in venetoclax combination with intensive induction (3 + 7) and consolidation chemotherapy in newly treated AML patients.
Isocitrate dehydrogenase (IDH) 1 and 2 are present in the citric acid cycle. About 20% of AML patients carry IDH1 or IDH2 mutations that result in the reduction of alpha-ketoglutaric acid to 2-hydroxyglutaric acid (2-HG), which methylates intracellular histones and inhibits TET2 activity to hypermethylate DNA, thereby affecting gene expression and cell differentiation. IDH mutations are more common in older patients, are often cytogenetically-related, and can also co-occur with FLT3-ITD, NPM1, or DNMT3A mutations. Ivosidenib is an IDH1 inhibitor, and its safety and efficacy in the treatment of AML have been confirmed in previous studies. Based on the study of Montesinos et al. on the role of ivosidenib and azacitidine in IDH-mutated AML, for patients who cannot tolerate intensive chemotherapy, a new treatment regimen has been added for AML patients with IDH1 mutation: ivosidenib combined with azacitidine can be selected for 1 cycle every 28 days or ivosidenib monotherapy.
Therefore, this study intends to conduct a multi-center, single-arm clinical study to determine the maximum tolerated dose of ivosidenib and venetoclax combined chemotherapy, and the composite complete response rate, the negative conversion rate of MRD measured by flowcytometry and IDH1 mutant.

开始日期2025-10-30

申办/合作机构

中国医学科学院血液病医院

NCT07007312

/ Not yet recruiting临床3期

Phase 3 Randomized, Double-blind, Placebo-controlled Studies Assessing Ziftomenib in Combination With Either Standard of Care Nonintensive (Venetoclax+Azacitidine) or Intensive (7+3) Therapy in Patients With Untreated NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia

Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with eligible genetic alterations. Ziftomenib is a type of therapy known to target the menin pathway in cancer cells.
This protocol has 2 separate studies that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) AML treatments in patients with certain genetic mutations who have not received any treatment for their AML. In the first study, the Nonintensive Therapy Study, older patients or those with serious medical problems will receive the SOC therapies venetoclax (ven) and azacitidine (aza), plus either ziftomenib or a placebo. In the second study, the Intensive Therapy Study, medically fit patients will receive (a) the SOC therapies cytarabine and daunorubicin, plus either ziftomenib or a placebo during a first treatment phase called induction, (b) cytarabine plus either ziftomenib or a placebo during a second treatment phase called consolidation, and (c) ziftomenib or a placebo during a third treatment phase called maintenance.
The physician will determine which study is the appropriate treatment for the patient, but neither the patient nor their physician will know whether the patient has been assigned to receive ziftomenib or a placebo. This design is called "double-blinded".

开始日期2025-09-01

申办/合作机构

Kura Oncology, Inc.

NCT05554419

/ Not yet recruiting临床2期IIT

Eradicating Measurable Residual Disease in Patients With Acute Myeloid Leukemia (AML) Prior to StEm Cell Transplantation (ERASE): A MyeloMATCH Treatment Trial

This phase II MyeloMATCH treatment trial compares cytarabine versus (vs.) cytarabine and venetoclax vs. liposome-encapsulated daunorubicin-cytarabine and venetoclax vs. azacitidine and venetoclax for treating patients who have residual disease after treatment for acute myeloid leukemia (AML). Cytarabine is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. 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. Liposome-encapsulated daunorubicin-cytarabine is a drug formulation that delivers daunorubicin and cytarabine in small spheres called liposomes, which may make the drugs safer or more effective. Azacitidine is a drug that interacts with DNA and leads to the activation of tumor suppressor genes, which are genes that help control cell growth. This study may help the study doctors find out if the different drug combinations are equally effective to the usual approach of cytarabine alone while requiring a shorter duration of treatment. To decide if they are better, the study doctors will be looking to see if the study drugs lead to a higher percentage of patients achieving a deeper remission compared to cytarabine alone.

开始日期2025-08-29

申办/合作机构

National Cancer Institute

100 项与阿扎胞苷相关的临床结果

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100 项与阿扎胞苷相关的转化医学

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100 项与阿扎胞苷相关的专利（医药）

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9,421

项与阿扎胞苷相关的文献（医药）

2025-12-31·ANNALS OF MEDICINE

Significant prognostic improvement in elderly patients with acute myeloid leukemia treated with hypomethylating agents and venetoclax: outcomes from a retrospective real-world analysis

Article

作者: Wu, Yong ; Zheng, Jing ; Wu, Lanlan ; Chen, Yi ; Zhou, Jiayi ; Wu, Zhengjun ; Cai, Ruyu ; Wang, Zhengyang

OBJECTIVE:

This investigation aim to analyze the clinical features and therapeutic outcomes of elderly patients with acute myeloid leukemia (AML).

METHOD:

We conducted a retrospective analysis of the clinical and cytogenetic profiles of patients aged 60 years and older diagnosed with AML at the Fujian Medical University Union Hospital from 2016 to 2024.

RESULTS:

Our study cohort included 846 patients, with a median age of 67 years. The median duration of response (DOR) was 15.8 months, with 1-year, 3-year, and 5-year DOR rates of 55.3%, 23.4%, and 13.1%, respectively. The median overall survival (OS) was 21.8 months, with corresponding 1-year, 3-year, and 5-year OS rates of 58.7%, 41.2%, and 30.0%. Patients who received the azacitidine and venetoclax treatment protocol exhibited a complete remission (CR) rate of 57.1% and a minimal residual disease (MRD) - negative rate of 34.1%. These rates were comparable to the 59.2% CR rate and 39.4% MRD-negative rate observed in patients treated with intensive chemotherapy, and were superior to those with other low-intensity regimens. Compared to the treatment outcomes achieved at our center prior to 2016, when chemotherapy was the predominant treatment modality, which were characterized by a CR rate of 42.7%, a median OS of 9.2 months, and a mere 5-year OS rate of 13.5%, the remission rate and long-term survival of elderly patients with AML have been remarkable improved.

CONCLUSION:

The integration of hypomethylating agents and venetoclax into the treatment paradigm for elderly patients with AML has significantly enhanced survival rates.

2025-12-31·Hematology

Identification of t(X;1)(q28;q21) generating a novel GATAD2B::MTCP1 gene fusion in CMML and its persistence during progression to AML

Article

作者: Chen, Yu ; Zhu, Yi-yan ; Liu, Yi-zi ; Hou, Chun-xiao ; Zhang, Zhi-yu ; Chen, Su-ning ; Wang, Qian ; Zhang, Feng-hong

OBJECTIVE:

Hematological malignancies often involve chromosomal translocations and fusion genes that drive disease progression. While MTCP1 is well-known in T-cell prolymphocytic leukemia (T-PLL), its role in myeloid neoplasms is less understood. This report presents the first identification of the t(X;1)(q28;q21) translocation leading to the GATAD2B::MTCP1 fusion in acute myeloid leukemia (AML) transformed from chronic myelomonocytic leukemia (CMML).

METHODS:

The karyotypes were described according to the International System for Human Cytogenetic Nomenclature 2009. We performed targeted next-generation sequencing (NGS) on a panel of 172 genes commonly mutated in hematological malignancies (Supplemental Table 1), using an Illumina platform. RNA sequencing was conducted on total RNA extracted from bone marrow, also using the Illumina platform. The GATAD2B::MTCP1 fusion gene was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing, with specific primers for the fusion transcript (GATAD2B-F: CCTCTTTTTTTCGACGCC; MTCP1-R: ACTGAGCACAACACTTACGC).

RESULTS:

The GATAD2B::MTCP1 fusion results from a breakpoint on 1q21 within GATAD2B exon 1 and Xq28 within MTCP1 exon 2. The patient with the GATAD2B::MTCP1 fusion exhibited disease progression from CMML to AML. Despite achieving initial remission with venetoclax-based therapy and allo-HSCT, the patient relapsed and died.

CONCLUSIONS:

We propose that the GATAD2B::MTCP1 fusion upregulates MTCP1 expression rather than generating a fusion protein, thereby contributing to transformation and relapse in AML. Further investigations are needed to elucidate the precise role of this fusion event in myeloid malignancies.

2025-12-01·MOLECULAR BIOLOGY REPORTS

Effects of 5-azacytidine and N6-methyladenosine combination on apoptosis and stemness in human breast cancer stem cells

Article

作者: Mukhtarova, Gunel ; Angin, Mesude ; Caner, Ayse ; Gunduz, Cumhur

BACKGROUND:

This study investigates the combined effects of the epigenetic anticancer drug 5-azacytidine (5-Aza) and N6-methyladenosine (m6A) on breast cancer stem cells (CSCs) and normal breast epithelial cells. CSCs are characterized by their ability to self-renew, their resistance to conventional therapies, and their role in metastasis, presenting a significant challenge in breast cancer treatment.

METHODS AND RESULTS:

The study utilized flow cytometry to isolate CD44 + /CD24low CSCs from MCF-7 breast cancer cells and evaluated these cells through spheroid formation assays. The results demonstrated that both 5-Aza and m6A, both individually and in combination, exert cytotoxic effects on CSCs, induce apoptosis, and reduce their migratory capacity. Importantly, these treatments did not produce similar effects on normal breast epithelial cells (MCF-10A), indicating selective action on CSCs. Gene expression analysis revealed that treatment with 5-Aza, m6A, and their combination altered the expression of key stem cell-related genes, including OCT4, NANOG, SOX2, and c-MYC, which are associated with CSC self-renewal and malignancy.

CONCLUSIONS:

These findings suggest that epigenetic modulation through 5-Aza and m6A could effectively target CSCs, disrupting their ability to drive tumor progression and metastasis, particularly in aggressive breast cancer subtypes. This study highlights the potential of 5-Aza and m6A as a combinatorial therapeutic approach, offering a promising avenue for improving treatment outcomes in breast cancer patients, especially those with therapy-resistant disease. Further clinical investigation is needed to validate these findings and explore their therapeutic implications.

1,196

项与阿扎胞苷相关的新闻（医药）

2025-06-07

·药明康德

客观缓解率达100%的抗体疗法；100%降解目标蛋白的潜在“first-in-class”口服降解剂…… | 一周盘点

本期看点1. 靶向Clever-1的单克隆抗体bexmarilimab与标准治疗（SoC）联用治疗初治高危骨髓增生异常综合征（HR-MDS）患者的早期临床试验结果亮眼，客观缓解率（ORR）达100%。2. 口服靶向抗癌化合物ibrilatazar联合化疗治疗III/IV期鳞状非小细胞肺癌（SQ-NSCLC）患者的1/2a期临床试验结果积极，与历史对照相比，联合治疗组的中位总生存期（OS）接近翻倍（22.5个月对比11.3个月）。3. Kymera Therapeutics公司的口服STAT6降解剂KT-621在一项1期研究的所有≥50 mg的多剂量递增（MAD）组中表现积极，患者血液与皮肤中的目标蛋白均达成完全降解。Bexmarilimab：公布1期联合治疗试验数据Faron Pharmaceuticals公司宣布，其靶向Clever-1的单克隆抗体bexmarilimab的一项1期研究结果已发表在《柳叶刀-血液学》（Lancet Haematology）杂志上。该研究旨在评估bexmarilimab联合SoC治疗高危骨髓增生异常综合征和复发/难治性（r/r）急性髓系白血病（AML）患者的安全性和有效性。Bexmarilimab是Faron公司全资拥有的研究性免疫疗法，旨在通过靶向髓系细胞功能和激活免疫系统，克服对现有疗法的耐药性并优化临床疗效。Bexmarilimab能与巨噬细胞上的免疫抑制受体Clever-1结合，该受体有助于肿瘤生长和转移（即帮助癌症躲避免疫系统）。通过靶向巨噬细胞上的Clever-1受体，bexmarilimab可改变肿瘤微环境，将巨噬细胞从免疫抑制（M2）状态重编程为免疫刺激（M1）状态，上调干扰素的产生，启动免疫系统攻击肿瘤，使癌细胞对标准治疗敏感。此次公布的结果显示，bexmarilimab联合阿扎胞苷在初治和低甲基化药物（HMA）治疗失败的HR-MDS患者中的ORR分别为100%和89%。HMA治疗失败的MDS患者的估计中位OS为13.4个月，r/r AML患者为8.1个月。两名HMA治疗失败的MDS患者在治疗后接受了造血干细胞移植（HSCT）。此外，治疗后患者的骨髓免疫生物标志物较基线水平提升了近3倍。在67%的HMA治疗失败的MDS患者中观察到HLA-DR分子增加，进一步支持bexmarilimab的作用机制。安全性方面，bexmarilimab联合治疗的耐受性良好，未观察到剂量限制性毒性。大多数治疗伴发不良事件（TEAE）为轻度至中度，仅6%与bexmarilimab相关。Ibrilatazar（ABTL0812）：公布1/2a期联合治疗试验数据AbilityPharma公司宣布，其评估ibrilatazar（ABTL0812）联合化疗（紫杉醇/卡铂）治疗III/IV期鳞状非小细胞肺癌患者的1/2a期临床试验ENDOLUNG的数据已发表在Lung Cancer杂志上。Ibrilatazar是一种潜在“first-in-class”、差异化的口服靶向抗癌化合物，通过诱导内质网应激和抑制PI3K/Akt/mTOR通路来引发自噬。在临床试验中，ibrilatazar对子宫内膜癌和肺癌患者显示出临床益处。此外，它在包括肺癌、子宫内膜癌、胰腺癌、神经母细胞瘤和胶质母细胞瘤等癌症类型的动物模型中展示了强有力的临床前概念验证。此次公布的结果显示，与历史对照相比，ibrilatazar联合化疗在所有疗效终点均显示出改善，包括：ibrilatazar联合治疗组的总缓解率为52%，历史对照为31.7%；ibrilatazar联合治疗组的中位无进展生存期（PFS）为6.2个月，历史对照为4.2个月；ibrilatazar联合治疗组的中位OS为22.5个月，历史对照为11.3个月。安全性方面，ibrilatazar联合化疗表现出良好的安全性。在紫杉醇/卡铂基础上加入ibrilatazar的安全性与历史对照中紫杉醇/卡铂单独使用时的安全性一致，并未带来除紫杉醇/卡铂本身已知不良事件之外的显著新增安全性风险。KT-621：公布1期临床试验数据Kymera Therapeutics公司公布其潜在“first-in-class”口服STAT6降解剂KT-621在1期健康受试者研究中的积极结果。数据显示，KT-621在每日一次口服给药下，于所有高于1.5 mg剂量水平中实现了超过90%的平均血液STAT6降解；在所有≥50 mg的MAD组中，更在血液与皮肤中均达成完全降解。此外，KT-621对Th2炎症相关生物标志物TARC和Eotaxin-3的中位降低幅度分别高达37%与63%，表现优于或相当于现有获批药物。KT-621在本项试验中展现出优异的安全性，未观察到严重不良事件或与治疗相关的不良事件，整体耐受性与安慰剂无明显差异。Kymera公司指出，KT-621的临床表现已显著优于其预设的产品特征目标，进一步验证了其“生物制品口服化”开发策略的可行性。当前，KT-621正在中重度特应性皮炎（AD）患者中开展1b期BroADen试验，预计将在2025年第四季度公布数据，并计划分别于2025年第四季度与2026年第一季度启动针对AD与哮喘的两项2b期临床研究。ISB 2001：公布1期临床试验的新数据Ichnos Glenmark Innovation公司公布了其三特异性抗体ISB 2001用于治疗复发/难治性多发性骨髓瘤（RRMM）的1期研究的新数据。ISB 2001同时靶向多发性骨髓瘤（MM）细胞上的BCMA和CD38，以及T细胞上的CD3，旨在增加对MM细胞的特异性结合，同时最大限度地减少脱靶效应。此次公布的结果显示，在经过大量治疗的患者群体中，7个活性剂量（≥50 μg/kg）组患者的持续总缓解率为79%，完全缓解/严格完全缓解（CR/sCR）率为30%。所有接受治疗的患者的总缓解率为74%，包括2例接受较低剂量治疗的患者。安全性方面，ISB 2001具有良好的安全性，大多数患者在数据截止时仍在接受治疗。EBC-129：公布1期临床试验的新数据新加坡实验药物研发中心（EDDC）公布了其在研抗体偶联药物（ADC）EBC-129的一项1期临床试验的新数据。EBC-129靶向CEACAM5和CEACAM6上保守的肿瘤特异性N256糖基化位点，这两种蛋白在肿瘤发生和转移中起关键作用。该ADC的毒性有效载荷是微管蛋白抑制剂MMAE，该药物已在其他上市的ADC中被广泛测试并获批用于临床，且已显示出与PD-1抑制剂之间的协同作用。此次公布的结果显示，EBC-129在21名此前接受过大量治疗的胰腺导管腺癌（PDAC）患者中显示出积极的总缓解率和延长的无进展生存期，包括那些之前接受过SoC（通常含有紫杉烷类药物）的患者。在接受1.8 mg/kg和2.2 mg/kg剂量治疗的患者中，总缓解率分别为25%和20%，疾病控制率（DCR）达87.5%和63.6%，中位PFS分别为19周和12周。EBC-129在迄今为止接受治疗的58例患者中显示出可控的安全性，观察到的主要治疗相关不良事件（TRAE）为无并发症的中性粒细胞减少和输液相关反应。IMC-002：公布1期联合治疗试验的中期数据ImmuneOncia Therapeutics公司公布了其下一代CD47靶向抗体IMC-002与lenvatinib联用治疗晚期肝细胞癌（HCC）患者的1b期临床试验的中期结果。IMC-002是一款全人源化IgG4单克隆抗体，通过阻断CD47-SIRPα相互作用，促进巨噬细胞对肿瘤细胞的吞噬作用。该抗体疗法可以在保证高疗效的同时最大限度地减少与红细胞的结合并避免血液学毒性。此次公布的结果显示，IMC-002表现出良好的安全性特征，未报告中性粒细胞减少或血小板减少，96%的不良事件为1/2级。在疗效可评估的10名患者中，有3名达到部分缓解（PR），DCR达80%，中位PFS为8.3个月。两名患者的治疗时间已超过一年，提示该疗法可能带来持久的临床获益。参考资料（可上下滑动查看）[1] ImmuneOncia Announces Interim Results from Phase 1b Clinical Trial of Next-Generation CD47 Antibody 'IMC-002' at ASCO 2025. Retrieved June 5, 2025, from https://www.prnewswire.com/news-releases/immuneoncia-announces-interim-results-from-phase-1b-clinical-trial-of-next-generation-cd47-antibody-imc-002-at-asco-2025-302470514.html[2] Pasithea Therapeutics Presents Updated Interim Data from Ongoing Phase 1 Study of PAS-004 at the ASCO Annual Meeting 2025. Retrieved June 5, 2025, from https://ir.pasithea.com/news-events/press-releases/detail/122/pasithea-therapeutics-presents-updated-interim-data-from[3] Allogene Therapeutics Provides Updated Phase 1 Data Highlighting Durable Responses with ALLO-316 in Heavily Pretreated Advanced Renal Cell Carcinoma at ASCO. Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/06/01/3091475/0/en/Allogene-Therapeutics-Provides-Updated-Phase-1-Data-Highlighting-Durable-Responses-with-ALLO-316-in-Heavily-Pretreated-Advanced-Renal-Cell-Carcinoma-at-ASCO.html[4] MYTX-011, a cMET-targeting antibody-drug conjugate (ADC), in patients with previously treated, advanced NSCLC: Updated dose escalation results in the phase 1 KisMET-01 study. Retrieved June 5, 2025, from https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8613[5] NervGen Pharma Reports Positive Topline Data from the Chronic Cohort of its Phase 1b/2a Clinical Trial Evaluating NVG-291 in Spinal Cord Injury. Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/06/02/3091725/0/en/NervGen-Pharma-Reports-Positive-Topline-Data-from-the-Chronic-Cohort-of-its-Phase-1b-2a-Clinical-Trial-Evaluating-NVG-291-in-Spinal-Cord-Injury.html[6] Kymera Therapeutics Announces Positive First-in-Human Results from Phase 1 Healthy Volunteer Clinical Trial of KT-621, a First-in-Class, Oral STAT6 Degrader. Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/06/02/3091701/0/en/Kymera-Therapeutics-Announces-Positive-First-in-Human-Results-from-Phase-1-Healthy-Volunteer-Clinical-Trial-of-KT-621-a-First-in-Class-Oral-STAT6-Degrader.html[7] Erasca Announces IND Clearance for Potential First-in-Class and Best-in-Class Pan-KRAS Inhibitor ERAS-4001. Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/06/02/3091800/0/en/Erasca-Announces-IND-Clearance-for-Potential-First-in-Class-and-Best-in-Class-Pan-KRAS-Inhibitor-ERAS-4001.html[8] Diakonos Oncology Presents Promising Phase I Results of Dubodencel (DOC1021) for the Treatment of Glioblastoma at the ASCO 2025 Annual Meeting. Retrieved June 5, 2025, from https://www.prnewswire.com/news-releases/diakonos-oncology-presents-promising-phase-i-results-of-dubodencel-doc1021-for-the-treatment-of-glioblastoma-at-the-asco-2025-annual-meeting-302469896.html[9] GV20 Therapeutics Presents Updated Phase 1 Monotherapy Data on GV20-0251 at the ASCO Annual Meeting 2025. Retrieved June 5, 2025, from https://www.prnewswire.com/news-releases/gv20-therapeutics-presents-updated-phase-1-monotherapy-data-on-gv20-0251-at-the-asco-annual-meeting-2025-302463359.html[10] Mersana Therapeutics Reports Additional Positive Interim Phase 1 Clinical Data for Emi-Le in Oral Presentation at 2025 ASCO Annual Meeting. Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/06/02/3091831/0/en/Mersana-Therapeutics-Reports-Additional-Positive-Interim-Phase-1-Clinical-Data-for-Emi-Le-in-Oral-Presentation-at-2025-ASCO-Annual-Meeting.html[11] Merck Announces MK-1084, an Investigational KRAS G12C Inhibitor, Shows Antitumor Activity in Phase 1 Trial of Patients With Advanced Colorectal Cancer and Non-Small Cell Lung Cancer Whose Tumors Harbor KRAS G12C Mutations. Retrieved May 30, 2025 from https://www.merck.com/news/merck-announces-mk-1084-an-investigational-kras-g12c-inhibitor-shows-antitumor-activity-in-phase-1-trial-of-patients-with-advanced-colorectal-cancer-and-non-small-cell-lung-cancer-whose-tumors-harbo/[12] IN8bio Presents Positive Phase 1 Data of INB-200 in Newly Diagnosed GBM Demonstrating Prolonged Progression-Free Survival. Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/06/02/3091745/0/en/IN8bio-Presents-Positive-Phase-1-Data-of-INB-200-in-Newly-Diagnosed-GBM-Demonstrating-Prolonged-Progression-Free-Survival.html[13] OnCusp Therapeutics Announces Encouraging Initial Phase 1a Results from Ongoing First-in-Human Study Evaluating its CDH6-Directed Antibody-Drug Conjugate, CUSP06, in Platinum-Refractory/Resistant Ovarian Cancer and Other Advanced Solid Tumors at the 2025 ASCO Annual Meeting. Retrieved June 5, 2025, from https://www.prnewswire.com/news-releases/oncusp-therapeutics-announces-encouraging-initial-phase-1a-results-from-ongoing-first-in-human-study-evaluating-its-cdh6-directed-antibody-drug-conjugate-cusp06-in-platinum-refractoryresistant-ovarian-cancer-and-other-advanced--302470621.html[14] Perspective Therapeutics Highlights Updated Interim Data from its Ongoing Phase 1/2a Clinical Trial of [212Pb]VMT-α-NET at the 2025 ASCO Annual Meeting. Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/05/30/3091346/0/en/Perspective-Therapeutics-Highlights-Updated-Interim-Data-from-its-Ongoing-Phase-1-2a-Clinical-Trial-of-212Pb-VMT-%CE%B1-NET-at-the-2025-ASCO-Annual-Meeting.html[15] AbCellera Receives Authorization from Health Canada to Initiate a Phase 1 Clinical Trial of ABCL575. Retrieved June 5, 2025, from https://investors.abcellera.com/news/news-releases/2025/AbCellera-Receives-Authorization-from-Health-Canada-to-Initiate-a-Phase-1-Clinical-Trial-of-ABCL575/default.aspx[16] Faron announces publication of full Phase I BEXMAB study data in Lancet Haematology. Retrieved June 5, 2025, from https://faron.com/releases-and-publications/faron-announces-publication-of-full-phase-i-bexmab-study-data-in-lancet-haematology/[17] Enterome presents positive Phase 1/2 MSS/pMMR metastatic colorectal cancer data in patients treated with EO4010 OncoMimics™ immunotherapy plus nivolumab at ASCO 2025. Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/05/30/3090836/0/en/Enterome-presents-positive-Phase-1-2-MSS-pMMR-metastatic-colorectal-cancer-data-in-patients-treated-with-EO4010-OncoMimics-immunotherapy-plus-nivolumab-at-ASCO-2025.html[18] Experimental Drug Development Centre Announces the Presentation of Updated Data from the Phase 1 Study of Antibody-Drug Conjugate EBC-129 at the 2025 Annual Meeting of the American Society of Clinical Oncology (ASCO). Retrieved June 5, 2025, from https://www.prnewswire.com/news-releases/experimental-drug-development-centre-announces-the-presentation-of-updated-data-from-the-phase-1-study-of-antibody-drug-conjugate-ebc-129-at-the-2025-annual-meeting-of-the-american-society-of-clinical-oncology-asco-302467763.html[19] Full Dose-Escalation Data Show Continued High Response Rates and Favorable Safety Profile of ISB 2001, a First-in-Class BCMA × CD38 × CD3 Trispecific Antibody, for the Treatment of Relapsed/Refractory Multiple Myeloma. Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/06/02/3091923/0/en/Full-Dose-Escalation-Data-Show-Continued-High-Response-Rates-and-Favorable-Safety-Profile-of-ISB-2001-a-First-in-Class-BCMA-CD38-CD3-Trispecific-Antibody-for-the-Treatment-of-Relap.html[20] Cardiff Oncology Announces Positive Data from Investigator-Initiated Trial of Onvansertib in Combination with Paclitaxel in Metastatic Triple-Negative Breast Cancer Presented at ASCO 2025. Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/06/02/3092323/0/en/Cardiff-Oncology-Announces-Positive-Data-from-Investigator-Initiated-Trial-of-Onvansertib-in-Combination-with-Paclitaxel-in-Metastatic-Triple-Negative-Breast-Cancer-Presented-at-AS.html[21] Lilly presents first clinical data for its investigational, next-generation FRα targeting ADC in platinum-resistant ovarian cancer at the 2025 ASCO Annual Meeting. Retrieved June 5, 2025, from https://www.prnewswire.com/news-releases/lilly-presents-first-clinical-data-for-its-investigational-next-generation-fr-targeting-adc-in-platinum-resistant-ovarian-cancer-at-the-2025-asco-annual-meeting-302470018.html[22] Arrowhead Pharmaceuticals Initiates Phase 1/2a Study of ARO-ALK7 for the Treatment of Obesity. Retrieved June 5, 2025, from https://ir.arrowheadpharma.com/news-releases/news-release-details/arrowhead-pharmaceuticals-initiates-phase-12a-study-aro-alk7[23] Obsidian Therapeutics Announces Positive Clinical Data from OBX-115 in Patients with Advanced Melanoma in Ongoing Multicenter Study at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved June 5, 2025, from https://obsidiantx.com/news-releases/obsidian-therapeutics-announces-positive-clinical-data-from-obx-115-in-patients-with-advanced-melanoma-in-ongoing-multicenter-study-at-the-2025-american-society-of-clinical-oncology-asco-annual-meet/[24] Johnson & Johnson unveils first-in-human results for pasritamig, showing early anti-tumor activity in prostate cancer. Retrieved June 5, 2025, from https://www.prnewswire.com/news-releases/johnson--johnson-unveils-first-in-human-results-for-pasritamig-showing-early-anti-tumor-activity-in-prostate-cancer-302470142.html[25] Initial Data from the ARC-20 Study of Casdatifan Plus Cabozantinib Showed Nearly Half of Patients with Metastatic Kidney Cancer Had a Confirmed Response. Retrieved June 5, 2025, from https://www.businesswire.com/news/home/20250601016939/en/Initial-Data-from-the-ARC-20-Study-of-Casdatifan-Plus-Cabozantinib-Showed-Nearly-Half-of-Patients-with-Metastatic-Kidney-Cancer-Had-a-Confirmed-Response[26] 에이비엘, 'B7-H4x4-1BB' 삼중 1b/2상 "국내 IND 승인". Retrieved June 5, 2025, from https://www.biospectator.com/news/view/25313[27] Sionna Therapeutics Announces Positive Phase 1 Data for NBD1 Stabilizers SION-719 and SION-451 and Advances Both Programs in Clinical Development for Cystic Fibrosis. Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/06/04/3093440/0/en/Sionna-Therapeutics-Announces-Positive-Phase-1-Data-for-NBD1-Stabilizers-SION-719-and-SION-451-and-Advances-Both-Programs-in-Clinical-Development-for-Cystic-Fibrosis.html[28] Moleculin Reports Positive Topline Efficacy Results from U.S. Phase 1B/2 Clinical Trial Evaluating Annamycin for the Treatment of Soft Tissue Sarcoma Lung Metastases (MB-107). Retrieved June 5, 2025, from https://www.globenewswire.com/news-release/2025/06/04/3093575/0/en/Moleculin-Reports-Positive-Topline-Efficacy-Results-from-U-S-Phase-1B-2-Clinical-Trial-Evaluating-Annamycin-for-the-Treatment-of-Soft-Tissue-Sarcoma-Lung-Metastases-MB-107.html[29] REGENXBIO REPORTS NEW POSITIVE FUNCTIONAL DATA FROM PHASE I/II AFFINITY DUCHENNE® TRIAL OF RGX-202. Retrieved June 5, 2025 from https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-reports-new-positive-functional-data-phase-iii[30] AbilityPharma’s IBRILATAZAR (ABTL0812) doubles overall survival in patients with squamous non-small cell lung cancer. Retrieved June 5, 2025 from https://abilitypharma.com/en/main-menu/media-center-2/press-release/abilitypharma%E2%80%99s-ibrilatazar-(abtl0812)-doubles-overall-survival-in-patients-with-squamous-non-small-cell-lung-cancer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：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2

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亚盛医药第二款大药蓄势出海

产品出海已成为驱动本轮创新药行情反转的核心逻辑。典型案例如三生国健，就SSGJ-707与辉瑞达成授权后，短短半个月内股价即实现翻倍。亚盛医药自去年年中与武田就奥雷巴替尼达成授权合作以来，股价便开启强劲上涨通道。自2024年6月至今，其累计涨幅已达260%。这项被业界誉为“史诗级BD大单”的交易，不仅助推亚盛医药市值突破190亿，更带来了极为亮眼的财务表现——2024年公司营收同比激增342%，达到9.81亿元。在奥雷巴替尼的授权成功之后，亚盛医药的下一个重磅候选药物——新型Bcl-2抑制剂APG-2575，登场了。新引擎Bcl-2靶点的成药性挑战堪称肿瘤药物研发领域的“硬骨头”。其核心难点在于作用机制为蛋白-蛋白相互作用（PPI），靶点结合界面大且缺乏传统小分子药物可识别的“深口袋”结构，导致设计高亲和力抑制剂的难度极大。此外，Bcl-2蛋白定位于线粒体膜（细胞内最复杂的双膜结构），药物需先后跨越细胞膜和线粒体膜双层屏障才能发挥作用，进一步加剧了成药壁垒。自1972年靶点发现至今50余年，全球仅有艾伯维与罗氏联合开发的维奈克拉成功突围，成为首个也是唯一获批的Bcl-2抑制剂。亚盛医药自主研发的新型选择性Bcl-2抑制剂APG-2575（力胜克拉片）则开启了该领域的新征程。APG-2575新药上市申请（NDA）已于2024年11月获药品审评中心受理，并被推荐纳入优先审评程序，用于治疗难治或复发性慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）。APG-2575是首个在国内提交NDA的国产原研Bcl-2抑制剂，也有望成为继维奈克拉之后全球第二个上市的Bcl-2抑制剂。在2025年ASCO年会上，亚盛医药口头报告了APG-2575联合去甲基化药物阿扎胞苷（AZA）治疗初治或既往接受过维奈克拉治疗的髓系恶性肿瘤患者的1b/2期临床研究最新数据。数据显示，截至2025年4月，在28例既往维奈克拉耐药的复发/难治AML/混合表型急性白血病（MPAL）患者中，22例疗效可评估，总反应率（ORR）为31.8%（7/22），其中22.8%的患者达到完全缓解/完全缓解伴血细胞未完全恢复，4.6%的患者获部分缓解（PR），4.6%的患者获形态学无白血病状态（MLFS）。在6例疗效可评估的新诊断AML/MPAL患者中，ORR高达83.3%；在44例疗效可评估的R/R AML/MPAL患者中，ORR为43.2%。在骨髓增生异常综合征（MDS）及慢性粒单核细胞白血病（CMML）患者中，15例疗效可评估的ND患者ORR为80%，22例疗效可评估的R/R患者ORR为50%。安全性方面，APG-2575联合AZA治疗耐受性良好，安全性可控。值得关注的是，这是国际上首次报告一种Bcl-2抑制剂克服另一种Bcl-2抑制剂耐药的临床研究，表明APG-2575在髓系恶性肿瘤治疗领域具有显著的突破潜力。这不是APG-2575第一次显示出相对维奈克拉的差异化优势了。早在2024年美国血液学会年会上，亚盛医药就公布APG-2575单药或联合阿可替尼或利妥昔单抗治疗初治、复发/难治性或既往接受过维奈克拉治疗的CLL/SLL的临床数据。研究结果显示，在87例接受APG-2575联合阿可替尼治疗的患者中，ORR为96.6%；在既往接受过维奈克拉治疗的患者中，ORR为85.7%；而在既往接受过维奈克拉但未接受过BTK抑制剂治疗的患者中，ORR达到100%。这一结果表明，“APG-2575+BTK抑制剂”联用疗法相较于“Venetoclax+BTK抑制剂”具有潜在优势。凭借越来越多的循证医学证据，APG-2575展现出作为全球Best-in-class潜力品种应有的安全性和疗效。鉴于其优异的临床数据，APG-2575获2025版《CSCO淋巴瘤诊疗指南》推荐，用于单药治疗复发/难治性慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）患者。这是APG-2575首次纳入CSCO指南，也是唯一获得指南推荐的中国原研Bcl-2抑制剂，标志着亚盛医药在推动该创新品种惠及患者的道路上迈出了里程碑式的一步。在全球化布局方面，APG-2575正开展多项全球注册3期临床试验，包括获美国FDA许可的治疗经治慢性CLL/SLL患者的全球注册3期临床研究（GLORA）、治疗初治CLL/SLL患者的全球注册3期临床研究、一线治疗新诊断老年或体弱急性髓系白血病的全球注册3期临床研究，以及治疗新诊断中高危骨髓增生异常综合征患者的注册3期研究。此外，APG-2575已有5个适应症获得美国FDA授予的孤儿药资格认定，分别为华氏巨球蛋白血症、慢性淋巴细胞白血病、多发性骨髓瘤、急性髓系白血病和滤泡性淋巴瘤，彰显了其在国际肿瘤治疗领域的广泛潜力和认可。市场前景广阔维奈克拉2016年率先在美国上市，2020年12月落地中国市场。维奈克拉2023年全球销售额达22.88亿美元，2024年同比增长12.9%至25.83亿美元。艾伯维预测维奈克拉2026年峰值销售额将突破60亿美元。随着靶向细胞凋亡治疗领域的爆发，弗若斯特沙利文数据显示，全球该市场规模正以24%的复合年增长率高速扩张，预计2030年将突破220亿美元。在国产Bcl-2创新药赛道上，亚盛医药的APG-2575、百济神州的索托克拉片与诺诚健华的ICP-248是研发进度比较靠前的药物：APG-2575是国内首个提交上市申请的原研Bcl-2抑制剂，其临床数据展现出对维奈克拉耐药患者的突破潜力，且兼具剂量爬坡快、半衰期短、安全性更佳等差异化优势。图片来源：亚盛医药索托克拉片于2025年4月申报上市，此次申报的适应症为经治CLL/SLL成人患者；接受过抗CD20治疗和BTKi治疗的套细胞淋巴瘤（MCL）成人患者。ICP-248正在中国和全球开展一系列临床试验，包括联合奥布替尼一线治疗CLL/SLL的注册性3期临床试验，以及治疗AML的临床试验等。从研发进度看，亚盛医药凭借更早的NDA申报时间（早于百济神州的索托克拉片）和更靠前的审批状态，有望率先实现国产Bcl-2抑制剂零的突破，成为全球第二款上市药物。这一先发优势在当前只有维奈克拉获批且在售的市场格局下尤为关键——APG-2575不仅填补了国产同类药物的空白，更使其成为国际license-out的热门标的，未来在全球细胞凋亡治疗市场中具备显著商业想象空间。表1 全球Bcl-2抑制剂研发进度数据来源：药智数据向全球化进阶亚盛医药作为聚焦细胞凋亡通路的创新药企，已构建起覆盖肿瘤、代谢疾病等领域的多元化产品管线，核心布局包括Bcl-2、MDM2-p53等凋亡通路关键靶点抑制剂，以及针对激酶突变体的新一代靶向药物。2024年公司研发投入同比增长34%至9.47亿元，持续加码创新药研发。核心产品奥雷巴替尼（耐立克）是国内首个第三代BCR-ABL抑制剂，主要用于治疗伴有T315I突变的慢性髓细胞白血病（CML）慢性期（-CP）和加速期（-AP）患者，以及对第一代和第二代酪氨酸激酶抑制剂耐药或不耐受的CML-CP患者。自2021年11月上市后，相关适应症均纳入国家医保目录，2024年销售额同比增长52%至2.41亿元。在国际化进程中，耐立克已获美国FDA快速通道资格及孤儿药认证，其全球注册3期研究（POLARIS-2）正针对经治CML-CP患者展开，预计2026年申报美国上市，有望成为全球第二个上市的第三代BCR-ABL抑制剂。此外，耐立克联合治疗Ph+ALL及SDH缺陷型GIST的全球3期研究同步推进，早期数据显示其在TKI耐药患者中部分缓解率达25%，安全性与抗肿瘤活性兼具。东吴证券预测其海外峰值销售有望突破10亿美元。亚盛医药以凋亡通路为核心，形成多靶点、多适应症的研发梯队：Alrizomadlin为公司细胞凋亡管线重点品种，是首个在中国进入临床阶段的MDM2-p53抑制剂。2025年ASCO年会数据显示，其单药或联合PD-1抑制剂治疗晚期腺样囊性癌（ACC）等实体瘤时，单药组12例ACC患者ORR为16.7%，DCR达100%；联合治疗组6例胆道癌患者ORR为16.7%，DCR 100%，展现出可控安全性与初步疗效。APG-2449是小分子FAK/ALK/ROS1三联激酶抑制剂，2025年AACR大会数据显示，其联合一线/二线化疗在小细胞肺癌模型中可增强DNA损伤并诱导细胞凋亡，显示协同抗肿瘤效应。APG-5918是一款胚胎外胚层发育蛋白抑制剂，在2025年AACR大会上亚盛医药发布了关于该候选药物在前列腺癌临床前模型中的抗肿瘤活性及其与雄激素受体抑制剂恩扎卢胺的协同作用研究。截至目前，公司4个在研新药共获16项FDA和1项欧盟孤儿药资格认定，2项FDA快速通道资格以及2项FDA儿童罕见病资格认证。依托强大的知识产权布局，亚盛医药与武田、默沙东、阿斯利康等跨国药企，以及梅奥医学中心、丹娜法伯癌症研究院等顶尖学术机构建立全球合作。2025年1月24日，亚盛医药成功登陆美国纳斯达克主板，成为2025年全球生物医药第一股，亦是首家实现港股、美股双重主要上市的生物药企。本次IPO募资净额约1.325亿美元（约合人民币9.67亿元），为研发与商业化注入强劲动力，标志着其全球化战略进入新阶段。2024年亚盛医药实现收入9.81亿元，同比增幅达342%，主要得益于奥雷巴替尼的销售增长及技术授权收入。在创新药研发与商业化双轮驱动下，公司正以细胞凋亡通路为核心，加速向全球领先的生物制药企业迈进。结语展望未来，随着APG-2575等重磅品种的陆续上市、全球3期研究的持续推进，以及与跨国药企及顶尖学术机构的深度合作，亚盛医药有望在全球肿瘤治疗领域开拓更多“中国方案”。参考资料：1、各公司官网2、东吴证券3、药智数据声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 史蒂文合作、投稿、转载开白 | 马老师 18323856316（同微信）阅读原文，是受欢迎的文章哦

ASCO会议优先审批申请上市财报临床1期

2025-06-06

·氨基观察

Bcl-2抑制剂大变局

氨基观察-创新药组原创出品作者 | 蔡九随着国产创新药的崛起，全球创新药既有格局正加速迎来挑战与重塑。以Bcl-2抑制剂赛道为例，尽管艾伯维的维奈克拉凭借先发优势占据全球市场主导地位，且该领域因技术门槛极高被视为“难攻之城”，但国内药企并未望而却步，反而以雄心壮志加速追赶，率先“上岸”者已近在眼前。亚盛医药的新型Bcl-2选择性抑制剂APG-2575（Lisaftoclax）在去年年底已向CDE递交新药上市申请并获纳入优先审评，目前正处于获批倒计时阶段。值得关注的是，国内药企早已跨越“盲目跟随”的阶段，所遵循的是以技术创新驱动市场突破的底层逻辑。也正因此，不管是患者还是投资者，对国产Bcl-2抑制剂都有较高期待。例如，领跑者APG-2575过去已经展现了全面的疗效和安全性优势，有best-in-class潜力。如今看来，这些国产分子也并没有辜负市场期待。亚盛医药2025年ASCO大会上披露的最新数据显示，APG-2575针对维奈克拉治疗失败患者仍然展现了极为强劲的疗效，进一步颠覆了市场对其潜在“更好”的认知。这继续推升了APG-2575的市场关注度。在6月6日亚盛医药举办的2025 年ASCO年会解读会上，氨基君观察到，参会的机构分析师与投资者不仅人数众多，且展现出极高的关注热情。提问环节中，他们围绕APG-2575 的竞争壁垒、后续研发节点等核心议题展开了层层深入的追问。越来越多的人已经意识到，Bcl-2抑制剂赛道变局将至。/ 01 /继续刷新战斗力认知对于APG-2575的战斗力，市场早有认知。在2021年，APG-2575就率先开始探索r/r CLL/SLL患者的临床。根据公司2023年ASH年会上公布的数据，APG-2575在既往接受过深度治疗、且BTK经治的CLL患者中疗效显著。结果表明，在45例r/r CLL患者中，ORR和CR/CRi分别为73.3%和24.4%，CR/CRi率随剂量水平的增加呈上升趋势，mPFS为18.53个月，第30个月时的OS发生率为86.3%。上述患者近半数接受过>=3线治疗，基线较差，APG-2575仍展现出高缓解率的特点，凸显了其竞争力。2024年11月，APG-2575递交上市申请，有望成为全球第二款获批的Bcl-2抑制剂。而最新公布的ASCO数据，则是在更多维度证明了APG-2575的潜力。该Ib/II期临床试验，主要评估APG-2575联合去甲基化药物阿扎胞苷，治疗初治（TN）或既往接受过维奈克拉治疗的髓系恶性肿瘤患者。数据的最大亮点在于，针对维奈克拉治疗失败的患者，APG-2575仍展现出极为强劲的疗效。在28例既往维奈克拉耐药的复发/难治性 AML/混合表型急性白血病（MPAL）患者中，22 例疗效可评估，总反应率（ORR）为 31.8%。值得关注的是，这是Bcl-2抑制剂领域首次通过临床数据证实同类药物可克服相互间耐药性，被市场视为开创性突破——尤其71%的应答患者携带TP53突变或复杂核型，这类患者通常临床治疗难度极大。这一数据不仅刷新了市场对APG-2575治疗潜力的认知，更为整个Bcl-2抑制剂赛道提供了 “克服耐药性” 的新范式，其临床价值与行业意义均被高度期待。当然，除了针对维奈克拉治疗失败患者，APG-2575在其它难治患者以及新诊患者中，均展示了强大的活性。在新诊断的AML/MPAL中，ORR达到83.3%，在新诊断的MDS/CMML中为80%。R/R队列显示，AML/MPAL的ORR为43.2%，MDS/CMML的ORR为50%，与当前标准旗鼓相当或可能更好。上述数据充分表明，APG-2575填补难治领域临床空白的能力此前被显著低估，尤其是结合其安全性优势综合考虑后。/ 02 /安全性优势的再验证Bcl-2抑制剂后来者的破局：疗效是基础，但更重要的是安全性风险的降低。众所周知，维奈克拉面临肿瘤溶解综合征（TLS）、给药剂量繁琐等痛点，制约了Bcl-2抑制剂的临床应用拓展。而APG-2575之所以让市场充满期待，核心在于其具备潜在安全性优势——TLS发生概率极低，无需采用每周剂量递增方案，用药方案更灵活，患者应答速度更快。亚盛医药在今年ASCO上公布的，治疗初治（TN）或既往接受过维奈克拉治疗的髓系恶性肿瘤患者 Ib/II期临床数据，则是再次验证了其安全性优势。在临床设计方面，APG-2575继续展现同类最优的剂量窗口。剂量窗是指药物能够有效治疗疾病且安全性可控的剂量范围，最大耐受剂量数值越高，代表药物的耐受性越好、治疗潜力越强。在上述Ib/II期临床中，试验共设置2个部分：第1部分以递增剂量（200、400、600或800mg每天一次 [QD]）给药；第2部分评估200、400或600mgQD的安全性和有效性。并且，临床结果显示，高剂量组APG-2575也能较好的平衡治疗效果和安全性。根据公司相关人士在解读会上透露，600mgQD剂量将会是髓系恶性肿瘤3期临床考虑的剂量之一。而维奈克拉需通过繁琐的剂量爬坡，最终治疗剂量上限仅为400mg，相较之下，APG-2575的竞争力显著凸显。其次，APG-2575常见不良反应主要体现在血液学事件，非血液学毒性不常见，且绝大多数不良事件都可控制、可恢复、可耐受，进一步佐证了其安全性优势。在同类药物的临床研究中，因为毒副作用导致患者不耐受，一直是临床痛点。上述安全性数据表明，APG-2575能够为患者带来更优疗效和更持续的治疗周期，推动髓系恶性肿瘤向“慢性病管理”目标更进一步，这必然会进一步提升市场的期待值。/ 03 /对于未来的更高期待作为具备Best-in-Class潜力的分子，APG-2575 的市场上限令人遐想。当前研究布局与公布的成果显示，其目标不仅是追赶维奈克拉，更在于“维奈克拉能覆盖的群体，它能做得更好；维奈克拉不能覆盖的群体，APG-2575也能覆盖。凭借安全性和给药优势，APG-2575一方面展现了满足Bcl-2抑制剂主战场CLL/SLL领域更多患者需求。其联合阿可替尼治疗CLL/SLL的潜力显著。公司此前公布的2期研究结果显示，APG-2575与阿卡替尼联用治疗初治CLL/SLL患者的ORR达100%，在R/R CLL/SLL中的ORR仍达98%。不管在治疗CLL/SLL还是R/R CLL/SLL中，APG-2575联合疗法均可能最佳选择更重要的是，联合治疗保持了与APG-2575单药治疗相当的安全性：临床TLS发生率低、后遗症小，主要为临床易于管理的低级别血液学不良事件。此外，APG-2575联合BTKi的给药方案更简洁便利，采用每日梯度剂量递增给药，改进了维奈克拉联合方案特有的BTKi单药导入期，可更快进入联合治疗阶段，综合优势进一步凸显。基于此，针对BTK抑制剂耐药CLL/SLL患者、一线治疗初治CLL/SLL患者的多项全球注册3期研究均已开展。另一方面，APG-2575在MDS、R/R MM等维奈克拉尚未覆盖的领域也展现出极佳疗效。例如，亚盛医药在2024 年ASH 大会上口头汇报了APG-2575用于R/R MM或AL淀粉样变性患者的临床试验数据：在既往接受过多线治疗的36例可评估患者中，总ORR达63.9%， VGPR率达 30.6%，mPFS高达9.7个月。安全性方面，APG-2575在800-1200mg剂量下与其他药物联用时仍表现出良好耐受性，且未发生药物相互作用（DDI）。该研究是全球首个Bcl-2抑制剂在高剂量下长时间使用的研究报告。基于积极的表现，在AML和MDS适应症领域，lisaftoclax也均有全球注册3期临床正在开展。若能兑现全适应症布局，APG-2575在为全球患者提供更优选择的同时，销售峰值有望远超维奈克拉。这也预示了一点，Bcl-2抑制剂的下半场会更加精彩。PS：欢迎扫描下方二维码，添加氨基君微信号交流。

ASCO会议优先审批临床结果申请上市临床1期

100 项与阿扎胞苷相关的药物交易

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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,

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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,

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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

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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


NCT00629343 (CTgov)	临床1期	恶性间皮瘤 \| 软组织肉瘤	27	Temozolomide+Azacitidine	範顧獵選壓襯壓鹽蓋蓋 = 夢夢壓糧窪膚構網壓獵鹹衊鏇夢窪窪鑰顧鏇鏇 (顧繭獵醖鹽鹽鑰鏇築蓋, 構窪築製艱範顧夢膚醖 ~ 衊積廠構襯願襯醖艱遞) 更多	-	2025-06-05
NCT02124174 (ASCO2025)	临床2期	急性髓性白血病 \| 高危骨髓增生异常综合征维持	50	Azacitidine	鑰繭顧鹹鏇簾顧遞構餘(鬱繭鏇夢積築選醖廠窪) = 選觸壓壓窪夢淵廠顧醖遞範齋壓製衊鹹積蓋醖 (餘顧餘淵獵鹹齋積憲簾 ) 更多	积极	2025-05-30
ASCO2025	N/A	高危骨髓增生异常综合征	105	azacitidine (Elderly patients (≥75 years))	願衊範窪鹹遞壓廠鬱齋(糧糧餘繭製構鏇醖壓淵) = Neutropenia, thrombocytopenia, and anemia rates were higher in older patients compared to younger patients. Treatment delays were more common in elderly patients, mostly due to infection complications. Causes of death were similar between the two groups, including disease progression, sepsis, febrile neutropenia, and pneumonia. 網齋製顧壓蓋構淵夢淵 (鹽膚壓窪網艱齋鏇構淵 )	积极	2025-05-30
ASCO2025	N/A	高危骨髓增生异常综合征	105	azacitidine (Younger patients (<75 years))		积极	2025-05-30
NCT04752163 (CTgov)	临床1/2期	复发性急性髓细胞白血病 \| 复发性急性淋巴细胞白血病 \| 慢性粒单核细胞白血病 ... 更多	17	DS-1594b (Phase I (DS-1594b) Cohort 1)	選齋膚遞網製觸遞壓憲 = 鹽廠遞壓築壓鑰衊願憲餘膚憲艱艱鬱餘鑰積築 (齋積遞膚襯醖遞築鏇觸, 餘構範積範選鹹糧獵蓋 ~ 夢觸築鹽鏇夢製積積醖) 更多	-	2025-05-23
NCT04752163 (CTgov)	临床1/2期	复发性急性髓细胞白血病 \| 复发性急性淋巴细胞白血病 \| 慢性粒单核细胞白血病 ... 更多	17	DS-1594b (Phase I (DS-1594b) Cohort 2)	選齋膚遞網製觸遞壓憲 = 廠襯繭艱廠觸齋艱觸鹽餘膚憲艱艱鬱餘鑰積築 (齋積遞膚襯醖遞築鏇觸, 憲範遞繭餘顧鑰夢獵繭 ~ 餘鹽繭遞遞鏇顧壓選鑰) 更多	-	2025-05-23
ATS2025	N/A	胸腔积液	-	Azacitidine	壓繭鏇製夢糧繭膚製廠(簾鏇簾窪繭憲構鹹窪選) = A case of a massive pleural effusion due to azacitidine therapy 壓選齋淵艱獵廠鹹淵艱 (窪範鹽窪獵糧觸衊餘壓 )	-	2025-05-16
NCT05428969 (BEXMAB, ASH2024) 人工标引	临床1/2期	骨髓增生异常综合征 TP53 Mutation	14	Bexmarilimab+Azacitidine	齋製構壓糧窪艱醖夢膚(壓網鏇艱艱窪繭繭積鏇) = 壓廠鏇鏇繭窪簾襯範餘製鹹壓獵糧膚願淵廠窪 (願窪淵夢積衊觸糧鏇鏇 ) 更多	积极	2024-12-09
ASH2024	N/A	急性髓性白血病	-	Azacitidine + Venetoclax	廠網鏇網衊簾觸蓋鏇網(醖鏇衊範選鑰醖齋選選) = 鹽膚簾齋願築鹽製襯廠廠艱製顧遞繭齋鏇鏇鏇 (壓範艱鹹衊餘膚淵繭構 ) 更多	-	2024-12-09
ASH2024	N/A	急性髓性白血病 \| 骨髓增生异常综合征	-	Azacitidine + Durvalumab	選獵選獵築蓋選鏇構鑰(醖製夢艱選壓糧願鹽艱) = 醖糧構簾選願窪繭衊窪夢顧窪糧遞餘簾鏇壓艱 (醖觸構範簾遞憲選鑰鬱 ) 更多	-	2024-12-09
ASH2024	N/A	急性髓性白血病 \| 骨髓增生异常综合征	-	Azacitidine	選獵選獵築蓋選鏇構鑰(醖製夢艱選壓糧願鹽艱) = 窪獵繭簾願鹽鏇憲鑰齋夢顧窪糧遞餘簾鏇壓艱 (醖觸構範簾遞憲選鑰鬱 ) 更多	-	2024-12-09
ASH2024	N/A	复发性急性髓细胞白血病	-	Venetoclax	積淵顧願繭夢遞夢衊鬱(襯膚遞餘糧繭醖範願淵) = 醖製鹽齋顧鹹鹽廠窪願襯壓淵顧餘繭鑰膚夢鹹 (膚衊窪鏇遞廠醖鏇選鑰, 6.2 ~ 16.0)	-	2024-12-09
ASH2024	N/A	急性髓性白血病	-	CC-486 (oral azacitidine) and venetoclax	顧衊窪顧糧網積蓋遞願(構壓遞襯鬱構壓廠觸繭) = G1-2 19%, G3-4 80% 憲鹹鬱鹽壓齋構鹽淵築 (廠夢製網鬱襯遞衊艱糧 ) 更多	-	2024-12-09