Asciminib as Single Agent or in Combination With Nilotinib in the 1st-line Treatment of BCR-ABL1+ Chronic Myeloid Leukemia: a Randomized GIMEMA-GELMC Phase II Study PEARL Study: PotEntial of Asciminib in the eaRly Treatment of CML

A phase 2, interventional, randomized unblinded study will be conducted in newly diagnosed CP CML patients, to investigate the efficacy and the safety of asciminib at a dose of 80 mg QD as single agent (arm A) or 40 mg BID in combination with nilotinib 300 mg BID (arm B).
All patients in both arm A and arm B will be treated for a minimum of 2 years (core phase). If they will have achieved a DMR (MR4), or if it will be in the interest of the patient, the treatment will be continued.
During the consolidation phase (2 years) asciminib will be continued at the same dose in both arms; in the combination arm the nilotinib dose will be reduced to 300 mg daily.
The patients maintaining a stable MR4 up to the end of the fourth year will discontinue the treatment (TFR phase). The rate of TFR at 5 year (1 year after discontinuation) will be evaluated.

开始日期2025-06-01

申办/合作机构

Gruppo Italiano Malattie EMatologiche dell'Adulto

NCT06684964

/ RecruitingN/A

Real-World Evidence Non-interventional Prospective Study for the Effectiveness, Tolerability and Adherence of Asciminib After Two Previous TKIs in Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) in Saudi Arabia. (ASC4REAL)

This is a non-interventional, prospective, observational single arm study describing the real-world effectiveness, tolerability, adherence, Healthcare Resource Utilization (HCRU) and Patient-Reported Outcome (PRO) data of asciminib in patients with Ph+ Chronic Myelogenous Leukemia - Chronic Phase (CML-CP) previously treated with ≥2 Tyrosine Kinase Inhibitor (TKIs) in routine clinical practice in Kingdom of Saudi Arabia.

开始日期2025-03-24

申办/合作机构

Novartis Pharmaceuticals Canada, Inc.

NCT06514534

/ Recruiting临床2期

A Phase II, Multi-center, Prospective, Open-label Study of Asciminib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) or Accelerated Phase (CML-AP) With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.

The objective of this Phase II study is to assess the potential of asciminib in managing CML-CP or CML-AP in patient carrying the T315I mutation. The presence of this mutation introduces treatment difficulties due to the limited available options. The study seeks to collect additional data on the effectiveness and safety of asciminib for these patients. By determining the drug's capacity to manage the disease and enhance patients outcomes, the study is designed to fill the unmet medical need and potentially offer a new therapeutic path for patients at a treatment deadlock.

开始日期2025-02-18

申办/合作机构

Novartis Pharmaceuticals Canada, Inc.

100 项与盐酸阿思尼布相关的临床结果

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100 项与盐酸阿思尼布相关的转化医学

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100 项与盐酸阿思尼布相关的专利（医药）

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325

项与盐酸阿思尼布相关的文献（医药）

2025-12-01·CANCER CHEMOTHERAPY AND PHARMACOLOGY

Population pharmacokinetic modeling of asciminib in support of exposure-response and ethnic sensitivity analyses in patients with chronic myeloid leukemia

Article

作者: Darstein, Christelle ; Sy, Sherwin K B ; Kawakita, Yasunori ; Wu, Shengyuan ; Yoon, Deokyong ; Grosch, Kai ; Yang, Yiqun ; Dasgupta, Kohinoor ; Kapoor, Shruti ; Hoch, Matthias

BACKGROUND:

The original population pharmacokinetics (popPK) model for asciminib in patients with chronic myeloid leukemia in chronic phase (CML-CP) was refined to address drug development needs in support of drug submission, namely, attainment of target drug exposure in specific patient populations, populating individual daily exposures for exposure-response analyses of key efficacy and safety endpoints, confirmation of comparability in exposure between 40 mg b.i.d. and 80 mg q.d., and assessment of ethnic insensitivity.

METHODS:

Participants from two organ dysfunction studies, patients with CML in blast and acute phases and acute lymphoblastic leukemia and patients from a phase III efficacy study in newly diagnosed Ph + CML-CP, and data from a dedicated phase II study in the Chinese patients previously treated with at least two prior tyrosine kinase inhibitors, and a phase IIIb study comparing two dose regimens of asciminib (40 mg b.i.d. and 80 mg q.d.) were included in the revised popPK model. Covariates evaluated were line of therapy, baseline renal and hepatic functions, Chinese or Japanese ethnicity.

RESULTS:

The apparent clearance and steady-state volume of distribution of asciminib were 6.84 L/h and 110 L, respectively, for a typical individual of 70 kg weight and 90 mL/min absolute glomerular filtration rate. Both the 40 mg b.i.d. and 80 mg q.d. resulted in a steady-state daily AUC of 12,600 ng.h/mL, and there was no difference between lines of therapy. Effects of renal or hepatic impairment on clearance were not clinically relevant. Chinese and Japanese exhibited similar PK as that of the global population.

CONCLUSIONS:

The 40 mg b.i.d. and 80 mg q.d. regimens are comparable in their daily exposure, supporting the use of the two dosing regimens in newly diagnosed and previously treated CML-CP patients. The PK of asciminib is insensitive to ethnic differences and no dose adjustment is required for severe renal and hepatic impaired patients.

2025-06-01·Clinical Lymphoma Myeloma & Leukemia

SOHO State of the Art Updates and Next Questions: Combination Therapy in Chronic Myeloid Leukemia in Chronic Phase

Review

作者: Costa, Alessandro ; Breccia, Massimo

Therapeutic strategies for chronic myeloid leukemia (CML) are rapidly evolving, with novel agents emerging to address the limitations of current treatments. Goals of CML management are disease control and achieve a deep and sustained molecular response for a possible successful treatment-free remission (TFR). However, a significant proportion of patients fail to reach adequate molecular response and require sequential therapies. A crucial aspect of treatment resistance lies in the persistence of leukemic stem cells (LSCs), which serve as a reservoir for disease recurrence. Increasing focus is placed on combination strategies to overcome the constraints of TKI monotherapy. Various strategies have been explored, starting with the combination of interferon (IFN) and TKIs. The investigation of alternative administration methods, dosing regimens, or extended treatment durations in clinical trials involving IFN represents potential avenues to address current conflicting results. Additionally, the combination of ATP-competitive TKIs with asciminib has shown encouraging preclinical and clinical results, with further data needed for a comprehensive safety profile. Recently, efforts to inhibit other signaling pathways have been explored but with contrasting results. Despite ongoing advancements, TKIs remain the cornerstone of both current and future combination therapies. Their integration with personalized approaches is crucial to overcome complex biological challenges and ensure long-term, effective and safe treatment for CML patients.

2025-06-01·American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

Which Is the Best Tyrosine Kinase Inhibitor for Newly Diagnosed Chronic Myelogenous Leukemia?

Review

作者: Hughes, Timothy P. ; Osborn, Michael ; Shanmuganathan, Naranie

The choice of frontline therapy for a patient with chronic phase chronic myeloid leukemia (CP-CML) can have a profound effect on the long-term clinical outcome. Currently, five tyrosine kinase inhibitors (TKIs—imatinib, dasatinib, nilotinib, bosutinib, and asciminib) are available for frontline therapy, but no single TKI is optimal for all patients. EUTOS long-term survival (ELTS) risk score, comorbidities, and treatment-free remission (TFR) priority are the key determinants of frontline TKI selection. Higher ELTS score, low age and comorbidity score, and a high priority for achievement of TFR would all favor the frontline use of a more potent TKI than imatinib. However, no TKI has improved survival compared with imatinib. In children with CP-CML, imatinib, dasatinib, and nilotinib have similar long-term efficacy, with ease of administration and impact of toxicities on quality of life being key considerations. Recent adult trials of reduced-dose dasatinib frontline showed that efficacy may be equivalent to standard-dose dasatinib with a better tolerability and safety profile, but experience is limited in patients with high-risk ELTS scores. The ASC4FIRST trial has confirmed that tolerability and molecular response with asciminib are superior to those with both imatinib and the second-generation (2G)-TKIs. While the overall treatment failure rate was lower with asciminib, the rate of BCR::ABL1 mutations that emerged with asciminib appeared to be higher. The risk of emergent mutations appears to be highly associated with the presence of ASXL1 mutations in the CML cells at diagnosis, but more work is needed to understand the implications of this finding.

270

项与盐酸阿思尼布相关的新闻（医药）

2025-06-22

·药明康德

3个月一次，降低发作率95%的单抗疗法；使超80%肿瘤患者获完全缓解的靶向疗法…… | 一周盘点

本期看点1. 潜在“first-in-class”突变型钙网蛋白（mutCALR）靶向单克隆抗体早期临床数据积极，超80%骨髓增殖性肿瘤（MPN）患者达完全缓解（CR）。2. 血浆激肽释放酶单抗抑制剂navenibart用于治疗遗传性血管性水肿，在一项早期临床试验中使患者每月的发作率大幅降低，平均降幅达92%，降幅中位数达97%。INCA033989：公布首个临床研究数据Incyte近日公布其创新疗法INCA033989的首个临床研究数据，该药物为一款潜在“first-in-class”、mutCALR靶向单克隆抗体，用于治疗携带此突变的骨髓增殖性肿瘤患者。数据显示，在接受INCA033989治疗的高危原发性血小板增多症（ET）的患者中，各剂量组均实现了快速且持久的血小板计数正常化，高剂量组（>400 mg）患者应答更为显著。其中，86%的患者达到完全或部分血液学缓解，82%达CR；89%（34/38）的可评估患者mutCALR等位基因频率（VAF）降低，且21%（8/38）患者在仅接受3个治疗周期后即实现超过50%的VAF下降。单细胞DNA测序探索性研究进一步显示，INCA033989能够选择性靶向并减少携带mutCALR的造血干祖细胞（CD34阳性）及髓红系细胞，同时促进正常（野生型CALR）细胞的恢复，支持健康造血功能的重建。骨髓活检结果亦验证了这一机制，mutCALR阳性巨核细胞减少、阴性巨核细胞增加。安全性方面，INCA033989在24至2500 mg的全部剂量范围内耐受性良好，无剂量限制性毒性（DLT），仅1例患者因治疗伴发不良事件（TEAEs）停药，另有1例发生剂量调整。最常见的TEAEs为疲劳（26.5%）和上呼吸道感染（20.4%），均为1-2级。Navenibart（STAR-0215）：公布1b/2期临床试验长期开放标签试验的数据Astria Therapeutics公司公布了其血浆激肽释放酶单抗抑制剂navenibart治疗遗传性血管性水肿的1b/2期临床试验长期开放标签试验的数据。此次公布的结果显示，患者每月的发作率大幅降低，平均降幅达92%，降幅中位数达97%。频率为每3个月给药一次组别患者的平均每月发作率降低了95%，而每6个月给药一次组别患者的平均降幅为86%。安全性方面，navenibart总体耐受性良好，无严重的治疗伴发不良事件，无停药现象。ELVN-001：公布1期临床试验的新数据Enliven Therapeutics公司公布其小分子激酶抑制剂ELVN-001治疗慢性粒细胞白血病（CML）患者的1期临床试验的新数据。ELVN-001是一种强效、高选择性、潜在“best-in-class”的小分子激酶抑制剂，专门针对CML患者的致癌驱动因子BCR-ABL融合蛋白。ELVN-001还具有针对耐药性最强的BCR-ABL1耐药突变体T315I和其他已知耐药突变体的活性。截至2025年4月28日的数据，在53例可评估的患者中，47%（25/53）在24周时达到主要分子学缓解（MMR），其中最后一线治疗时对酪氨酸激酶抑制剂（TKI）耐药的患者中有41%（14/34）在24周时处于MMR，曾接受asciminib或ponatinib治疗的患者中也有35%（12/34）在24周时处于MMR。所有达到或维持MMR的患者在数据截止时仍保持缓解。在该临床试验中所纳入的患者群体此前接受过大量治疗的情况下，ELVN-001与已获批的针对BCR-ABL融合蛋白的TKI在1期试验中所观察到的MMR相比，结果依然更好。安全性方面，ELVN-001在所有剂量水平上继续表现出良好的安全性和耐受性。BMF-500：公布1期临床试验的初步数据Biomea Fusion公司公布了其共价FLT3抑制剂BMF-500治疗复发/难治性急性白血病的初步临床数据。BMF-500是一种新型、口服可利用的、高效、具选择性的FLT3共价小分子抑制剂。此前的研究表明，BMF-500潜在的脱靶风险较小，对活化的FLT3突变（包括FLT3-ITD和各种酪氨酸激酶结构域突变）具有皮摩尔级的亲和力。在携带FLT3-ITD突变的急性髓系白血病（AML）小鼠模型中，BMF-500使小鼠的肿瘤完全消退，且不需要持续暴露即可维持疗效。BMF-500在治疗FLT3突变的复发/难治性急性白血病患者中表现出令人鼓舞的初步疗效。在可评估的11例FLT3突变患者中，9人出现骨髓原始细胞下降，5人降幅超过50%。同时，在FLT3野生型患者中也观察到疾病控制效果。所有接受治疗的FLT3突变患者（n=18）的中位总生存期（mOS）为3.8个月（无CYP3A4抑制剂）和3.5个月（有CYP3A4抑制剂）。该数据优于历史对照数据，接受过gilteritinib和venetoclax治疗失败后的复发/难治性FLT3突变AML患者的历史mOS仅为2.1个月。BMF-500在各个剂量水平上总体耐受良好，未报告剂量限制性毒性、QT间期延长或因治疗相关不良事件导致的停药。Misetionamide（GP-2250）：公布1期临床试验的中期数据Panavance Therapeutics公司公布了其小分子疗法misetionamide（GP-2250）联用吉西他滨治疗晚期不可切除或转移性胰腺导管腺癌患者1期临床试验的中期数据。Misetionamide具有独特的作用机制，可抑制两种致癌转录因子c-MYC和NFκB。此次公布的结果显示，与单独使用吉西他滨的历史结果相比，接受misetionamide联用吉西他滨治疗患者的确认的缓解率、疾病稳定率和无进展生存期更优，约42%的患者达到部分缓解或疾病稳定。此外，misetionamide联用吉西他滨的安全性良好，与单独使用吉西他滨的预期毒性相比，没有明显的新毒性或加剧的毒性。参考资料（可上下滑动查看）[1] Enliven Therapeutics Announces Updated Positive Data from Phase 1 Clinical Trial of ELVN-001 in CML at EHA 2025 Congress. Retrieved June 20, 2025, from https://www.prnewswire.com/news-releases/enliven-therapeutics-announces-updated-positive-data-from-phase-1-clinical-trial-of-elvn-001-in-cml-at-eha-2025-congress-302481050.html[2] Beam Therapeutics Announces New Data from BEACON Phase 1/2 Clinical Trial of BEAM-101 Supporting Differentiated Profile in Sickle Cell Disease (SCD) at European Hematology Association (EHA) 2025 Congress. Retrieved June 20, 2025, from https://www.globenewswire.com/news-release/2025/06/13/3098931/0/en/Beam-Therapeutics-Announces-New-Data-from-BEACON-Phase-1-2-Clinical-Trial-of-BEAM-101-Supporting-Differentiated-Profile-in-Sickle-Cell-Disease-SCD-at-European-Hematology-Associatio.html[3] U.S. Food & Drug Administration (FDA) Approves Investigational New Drug (IND) Application for Myrio's Lead Product (PHOX2B PC-CAR T) for the Treatment of Neuroblastoma. Retrieved June 20, 2025, from U.S. Food & Drug Administration (FDA) Approves Investigational New Drug (IND) Application for Myrio's Lead Product (PHOX2B PC-CAR T) for the Treatment of Neuroblastoma[4] Intellia Therapeutics Announces Positive Three-Year Data from Phase 1 Trial of Lonvoguran Ziclumeran (lonvo-z) in Patients with Hereditary Angioedema (HAE) at the European Academy of Allergy and Clinical Immunology Congress. Retrieved June 20, 2025, from https://www.globenewswire.com/news-release/2025/06/15/3099489/0/en/Intellia-Therapeutics-Announces-Positive-Three-Year-Data-from-Phase-1-Trial-of-Lonvoguran-Ziclumeran-lonvo-z-in-Patients-with-Hereditary-Angioedema-HAE-at-the-European-Academy-of-A.html[5] Vial Initiating Phase 1 Healthy Volunteer Trial of VIAL-TL1A-HLE, a Novel Subcutaneous Half-Life Extended Anti-TL1A Antibody for the Treatment of IBD and Other Inflammatory and Fibrotic Diseases. Retrieved June 20, 2025, from https://vial.com/updates/pr/vial-initiating-phase-1-healthy-volunteer-trial-of-vial-tl1a-hle/?[6] Lyell Immunopharma Announces Positive New Clinical Data Demonstrating High Rates of Durable Complete Responses from the Phase 1/2 Trial of LYL314 for the Treatment of Aggressive Large B-cell Lymphoma. Retrieved June 20, 2025, from https://www.globenewswire.com/news-release/2025/06/17/3100483/0/en/Lyell-Immunopharma-Announces-Positive-New-Clinical-Data-Demonstrating-High-Rates-of-Durable-Complete-Responses-from-the-Phase-1-2-Trial-of-LYL314-for-the-Treatment-of-Aggressive-La.html[7] Azitra Reports Promising Safety Data from Phase 1b Trial in Netherton Syndrome. Retrieved June 20, 2025, from https://www.prnewswire.com/news-releases/azitra-reports-promising-safety-data-from-phase-1b-trial-in-netherton-syndrome-302483136.html[8] 882-P - Eloralintide, a Selective, Long-Acting Amylin Receptor Agonist for Obesity—Phase 1 Proof of Concept. Retrieved June 16, 2025 from https://eppro02.ativ.me/src/EventPilot/php/express/web/planner.php?id=ADA25[9] Positive Late-Breaking Data for Incyte’s First-in-Class mutCALR-targeted therapy INCA033989 in Essential Thrombocythemia Presented at EHA2025. Retrieved June 16, 2025 from https://investor.incyte.com/news-releases/news-release-details/positive-late-breaking-data-incytes-first-class-mutcalr-targeted[10] Oncoinvent Announces Positive Final Data from Phase 1/2a Trial of Radspherin® in Patients with Colorectal Peritoneal Metastases. Retrieved June 16, 2025 from https://www.prnewswire.com/news-releases/oncoinvent-announces-positive-final-data-from-phase-12a-trial-of-radspherin-in-patients-with-colorectal-peritoneal-metastases-302484870.html[11] Zealand Pharma announces positive topline results from 28-week Phase 1b trial with GLP-1/GLP-2 receptor dual agonist dapiglutide. Retrieved June 16, 2025 from https://www.globenewswire.com/news-release/2025/06/18/3101731/0/en/Zealand-Pharma-announces-positive-topline-results-from-28-week-Phase-1b-trial-with-GLP-1-GLP-2-receptor-dual-agonist-dapiglutide.html[12] Spyre Therapeutics Announces Positive Interim Phase 1 Results for Two Next-Generation TL1A Antibody Programs, and Provides Clinical Development Updates Expected to Deliver 9 Phase 2 Readouts. Retrieved June 20, 2025 from https://www.prnewswire.com/news-releases/spyre-therapeutics-announces-positive-interim-phase-1-results-for-two-next-generation-tl1a-antibody-programs-and-provides-clinical-development-updates-expected-to-deliver-9-phase-2-readouts-302483628.html[13] Centessa Pharmaceuticals Announces Clearance of Investigational New Drug Application (IND) for ORX142, a Novel Orexin Receptor 2 (OX2R) Agonist; Clinical Data in Acutely Sleep-Deprived Healthy Volunteers Planned for this Year. Retrieved June 20, 2025 from https://investors.centessa.com/news-releases/news-release-details/centessa-pharmaceuticals-announces-clearance-investigational-new[14] Eolo Pharma Publishes First-in-Human Study in Nature Metabolism on Novel Obesity Drug Activating Energy-Burning Pathway. Retrieved June 20, 2025 from https://www.globenewswire.com/de/news-release/2025/06/16/3099684/0/en/Eolo-Pharma-Publishes-First-in-Human-Study-in-Nature-Metabolism-on-Novel-Obesity-Drug-Activating-Energy-Burning-Pathway.html[15] Debiopharm’s ADC Research Gains Momentum With Launch of First-in-human Trial Assessing Debio 1562M in Acute Myeloid Leukemia Patients. Retrieved June 20, 2025 from https://www.businesswire.com/news/home/20250616081884/en/Debiopharms-ADC-Research-Gains-Momentum-With-Launch-of-First-in-human-Trial-Assessing-Debio-1562M-in-Acute-Myeloid-Leukemia-Patients[16] Biomea Fusion Presents Updated Preliminary Clinical Data for Covalent FLT3 Inhibitor BMF-500 in Relapsed or Refractory Acute Leukemia at EHA 2025. Retrieved June 20, 2025 from https://investors.biomeafusion.com/news-releases/news-release-details/biomea-fusion-presents-updated-preliminary-clinical-data#:~:text=The%20presentation%20by%20Dr.%20Farhad%20Ravandi%20of%20The,inhibitor%2C%20in%20heavily%20pretreated%20patients%20with%20R%2FR%20AL.[17] Panavance Therapeutics Announces Promising Misetionamide (GP-2250) Phase 1 Clinical Trial Interim Findings in Pancreatic Cancer at BIO 2025. Retrieved June 20, 2025, from https://panavance.com/press/panavance-therapeutics-announces-promising-misetionamide-gp-2250-phase-1-clinical-trial-interim-findings-in-pancreatic-cancer-at-bio-2025/[18] Astria Therapeutics Announces Positive Initial Results from the ALPHA-SOLAR Long-Term Open-Label Trial of Navenibart in Hereditary Angioedema Patients at the European Academy of Allergy and Clinical Immunology Annual Congress. Retrieved June 20, 2025, from https://ir.astriatx.com/news-releases/news-release-details/astria-therapeutics-announces-positive-initial-results-alpha[19] Johnson & Johnson's dual-targeting CAR T-cell therapy shows encouraging first results in large B-cell lymphoma. Retrieved June 20, 2025, from https://www.prnewswire.com/news-releases/johnson--johnsons-dual-targeting-car-t-cell-therapy-shows-encouraging-first-results-in-large-b-cell-lymphoma-302480701.html[20] Galapagos Presented New Data at ICML 2025 From Cohort 3 of ATALANTA-1 in Relapsed/Refractory Indolent NHL Patients, Demonstrating High Complete Response and MRD Negativity Rates With CAR-T Candidate GLPG5101. Retrieved June 20, 2025, from https://www.globenewswire.com/news-release/2025/06/18/3101896/0/en/Galapagos-Presented-New-Data-at-ICML-2025-From-Cohort-3-of-ATALANTA-1-in-Relapsed-Refractory-Indolent-NHL-Patients-Demonstrating-High-Complete-Response-and-MRD-Negativity-Rates-Wit.html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

临床结果临床2期

2025-06-18

·医脉通

2025 EHA前沿 | 江倩教授：阿思尼布破局耐药与安全困境，CML靶向治疗的突破与展望

导读慢性髓性白血病（CML）是骨髓造血干细胞克隆性增殖形成的恶性肿瘤，占成人白血病的15%1。酪氨酸激酶抑制剂（TKIs）的出现极大地改善了患者的预后，使CML成为一种可治可控的慢性疾病。然而，传统TKIs由于选择性较差，容易导致脱靶，引发多种不良反应，从而导致治疗中断，影响患者的长期生存和生活质量。阿思尼布作为特异性靶向ABL1肉豆蔻酰口袋（STAMP）的BCR-ABL1抑制剂，因其结合位点的特异性在实现疗效提升的同时，脱靶效应更少2，为CML患者带来全新的治疗选择。2025年6月12-15日，第30届欧洲血液学会（EHA）年会在意大利米兰圆满落幕，来自全球多个国家的血液专家和专业人士汇聚一堂，共同探讨血液学领域的最新进展，本次会议公布了多项阿思尼布的最新研究成果。基于此，医脉通特邀北京大学人民医院江倩教授聚焦CML前沿进展与阿思尼布的临床突破，就未来CML的发展方向发表独到见解！医脉通：CML是一种由BCR-ABL融合蛋白驱动的恶性血液病，近年来，随着靶向治疗药物的迭代升级与诊疗理念的革新，CML领域取得突破性进展。本届EHA大会公布了众多关于CML的研究。能否请您结合前沿进展，谈谈近年来CML领域取得了哪些重大突破？江倩教授近年来，随着靶向治疗药物TKIs的出现和不断迭代，CML患者的临床结局已发生重大转变。第一代TKI的出现，使慢性期CML（CML-CP）患者的生存期延长并接近正常人群水平2。然而，CML临床实践中仍存在未被满足的需求，部分患者对一代TKI产生耐药，且存在诸多不良反应。为克服一代TKI的耐药问题，第二代TKI应运而生，尽管在疗效上有所提升，但其脱靶效应导致的不良事件更多，患者常需调整剂量2。在此基础上，第三代TKI进一步解决了二代TKI的耐药难题，但仍需优化安全性。由此可见，CML的药物研发均围绕未满足的临床需求展开，推动CML治疗向更高安全性、更优耐受性的方向持续探索。当前，研究者开发了新型STAMP药物——阿思尼布，与传统的TKIs不同，阿思尼布由于结合位点的特异性在实现疗效提升的同时，减少了脱靶效应，从而改善了治疗安全性和耐受性，为CML治疗带来全新选择。医脉通：在CML靶向治疗版图中，阿思尼布作为首个靶向ABL肉豆蔻酰口袋的BCR-ABL1抑制剂，是CML领域继现有TKI后取得的又一重大进展。本届EHA大会公布了阿思尼布在CML患者中的多维度研究数据，能否请您为我们介绍一下其中的亮点内容？江倩教授本届EHA会议公布了ASC4START研究的主要终点结果3，旨在头对头比较阿思尼布和第二代TKI尼洛替尼在新诊断CML-CP患者中的耐受性。结果显示，阿思尼布组与既往报道一致，未出现新的不良事件（AE），降低55%因AE停药风险（P=0.004）。阿思尼布组因AE或死亡导致的停药（5.6%和12.1%）、≥3级AE（25.0%和31.9%）和因AE导致剂量调整/中断（24.3%和30.1%）的发生率均低于尼洛替尼组。在疗效方面，阿思尼布组第12周的分子学反应率更高，包括BCR-ABL1IS≤10%（89.8%和82.0%）、BCR-ABL1IS≤1%（69.0%和52.5%）、主要分子学反应（MMR）（22.9%和10.2%）、分子学反应4（MR4）（4.6%和1.1%）和分子学反应4.5（MR4.5）（2.5%和0.4%）。此外，EHA会议还公布了ASC4FIRST研究48周时的分析结果4，比较新诊断CML-CP患者接受阿思尼布与研究者选择的一代或二代TKIs治疗后患者报告结局（PROs）的差异。结果显示，阿思尼布组在疲劳、疼痛、健康相关生活质量（HRQoL）、认知、社会功能、症状负担、对日常生活影响、担忧/情绪、身体形象以及对护理和信息的满意度方面均较TKIs组获益更多，发生疼痛和胃肠道相关不良事件（AE）的患者更少且症状更轻，这意味着接受阿思尼布治疗可获得更好的生活质量。综上，阿思尼布的耐受性及分子学反应更佳，在长期管理中，对患者的生活质量及症状改善更优，为新诊断CML-CP患者提供了兼具安全性与有效性的治疗选择。医脉通：基于坚实的循证医学证据，近期阿思尼布在我国正式获批CML一线治疗，这无疑是CML治疗领域的重大里程碑。您认为这一获批对于CML的整体治疗格局有着怎样深远的意义？江倩教授作为一种需长期用药的慢性病，CML的治疗亟需兼顾疗效与安全性的药物。尽管现有TKIs极大地改善了患者的预后，但从“活下来”到“活得好”的跨越，仍是当前临床治疗的核心诉求。近期，阿思尼布获得中国国家药品监督管理局（NMPA）批准，用于治疗新诊断的费城染色体阳性的慢性髓细胞白血病（Ph+CML）慢性期（CP）成人患者。阿思尼布的获批，不仅为CML患者提供了兼具疗效与安全性的一线治疗方案，并且打破了传统TKIs“疗效与毒性权衡”的困境，为追求高质量生活与长期治疗安全的患者提供了新选择，推动CML治疗理念从“生存延长”向“品质生存”升级，填补了临床未满足的需求。医脉通：作为该领域的权威专家，能否请您谈谈未来CML领域会朝着哪些方向进一步发展，以更好地满足患者的需求，提高患者的生活质量和长期生存率？江倩教授在新药研发方面，未来CML的药物研发需兼顾疗效和安全性，避免高毒性影响长期治疗，同时还需探索新型药物靶点或联合用药方案，为耐药的CML患者提供新的治疗选择。在个体化治疗方面，对于疗效良好但无法停药的CML患者，未来剂量优化将成为研究重点，临床需进一步探索合适的药物剂量，确保在维持疗效的同时减轻药物不良反应，为患者制定个体化给药方案。在精准医疗方面，精准检测技术将成为重要驱动力。例如，临床可通过应用数字PCR监测CML患者的深层分子学反应，为CML患者的治疗和停药决策提供更科学的依据。针对难治性耐药患者，临床可整合基因组、转录组等多组学数据，识别预后不良的分子特征，指导初始治疗方案选择与动态剂量调整。在以患者为中心的全生命周期管理方面，未来还需强化“以患者为中心”的医患沟通，中国CML患者更为年轻，对生活质量（如升学、就业、生育需求）改善和追求无治疗缓解（TFR）的愿望更强烈，临床医生需主动与患者进行充分沟通，深入了解患者的核心诉求与顾虑，共同决策治疗目标，并提供全程心理社会支持。此外，对于老年CML患者，临床则应关注合并症处理，实现CML治疗与基础疾病管理的协同优化。江倩教授医学博士，主任医师，二级教授，博士生导师北京大学人民医院血液科副主任北京大学人民医院青岛医院副院长国际CML基金会国家代表委员会成员国际白血病及相关疾病比较研究协会委员中华医学会血液学分会委员，白血病-淋巴瘤学组副组长北京医学会血液学分会主任委员中国抗癌协会中西整合白血病专业委员会主任委员中国医药教育协会白血病分会主任委员「参考文献」1.中华医学会血液学分会. 中华血液学杂志, 2020, 41（5） : 353-364.2.Hochhaus A, et al. N Engl J Med. 2024 Sep 12;391（10）:885-898.3.Andreas Hochhaus, et al. 2025 EHA. Abstract S166.4.Andreas Hochhaus, et al. 2025 EHA. Abstract PS1588.审批码ASC0048768-103321，有效期为2025-06-18至2026-06-17，资料过期，视同作废小调研撰写：Julia审校：Vera排版：Atai执行：Atai本平台旨在为医疗卫生专业人士传递更多医学信息。本平台发布的内容，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。如该等信息被用于了解医学信息以外的目的，本平台不承担相关责任。本平台对发布的内容，并不代表同意其描述和观点。若涉及版权问题，烦请权利人与我们联系，我们将尽快处理。

临床研究ASCO会议临床结果

2025-06-15

·ioncology

EHA速递：“2025 ELN 慢性髓系白血病管理推荐”首次公布更新要点

2025年6月12日，在第30届欧洲血液学会年会(EHA 2025)首日，Jane F Apperley教授发布了2025年版欧洲白血病网(European LeukemiaNet，ELN)慢性髓系白血病(CML)管理推荐的更新要点，针对CML的诊断、分期、预后、监测、耐药和BCR::ABL 突变、治疗、停药、妊娠、不良反应等问题进行了更新或强调。来自欧洲、北美、亚洲和澳大利亚的38名专家参与修订，基于2020年的版本，回顾了2020年之后发表的重要研究证据，超过75%的专家认可即达成一致，否则，在文中讨论或描述，形成了2025 ELN CML管理推荐。江倩教授特此整理，分享给大家。01疾病分期2022版WHO标准去除了加速期，而以往ELN标准中存在加速期。关于CML疾病分期中加速期的去留，引起了专家们的很大争议，未达到75%的推荐标准。因此，仅在2025 ELN CML推荐中进行了描述。以下是关于加速期的争议支持方遗传学研究显示CML是两种疾病状态；大多数加速期患者接受TKI单药治疗，反应和结局同慢性期；原始细胞20-30%的患者与急变期患者结局相似。反对方不应摒弃一个长期存在且被接受的疾病分期定义；该类型患者可能从强效TKI一线治疗中获益；影响未来对加速期的研究；影响新的研究结果与既往结果的对比分析。02疾病进展的高危因素▌诊断时高危ELTS评分、骨髓或外周血中原始细胞10-19%、外周血嗜碱性粒细胞＞20%、Ph阳性细胞中附加染色体异常(ACA，包括3q26.2、7/7q 、i(17q)、复杂核型等)。▌治疗中首次TKI治疗未达CHR、连续两种TKI耐药、出现新的染色体异常、BCR::ABL基因复杂突变。03疾病预后诊断时：1、高危ELTS评分(而非Sokal和Hasford/Euro评分)提示预后不良；2、ACA(3q26.2、7/7q 、+8，11q23，i(17q)，+17，+19，+21，+Ph，复杂核型)提示预后不良；3、BCR::ABL转录本类型的预后意义不明；4、BCR::ABL以外的体细胞突变的预后意义处于研究阶段，可能影响反应深度和无事件生存期，但不影响总生存期，尚缺乏明确的治疗指导意义。04监测强调治疗监测的目的1、防止或延缓疾病进展以改善生存期，识别可能预后不良的患者；2、识别适合追求停药缓解(TFR)的人群，他们不一定都是早期获得反应的患者。TKI治疗反应的里程碑中，原来的“Optimal”和”Failure”分别被“Favorable”和“Unfavorable”取代，保留了“Warning”。“Favorable”，即无须改变治疗；“Warning”，即治疗可能需要改变；“Unfavorable”，倾向于改变治疗。各时间点里程碑的定义保持未变，但强调：是否换药，不应仅凭单次的检测结果定义里程碑事件，而应该看趋势；某些被定义为“失败”的患者其实是慢反应型；老人或伴有共存疾病的患者要评估换药的获益和风险，换药可能对他们更为不利，更强效的TKI可能会增加不良反应风险;要明确为何换药，如是为了TFR或其他原因？05一线治疗1. 目前有多种药物选择。2. 多项研究表明，二代TKI在细胞遗传学和分子学反应以及防止进展入加速期/急变期等方面均有优势，但并没有改善患者的总生存期。3. 达沙替尼和尼洛替尼之间，未发现治疗反应、疾病进展和生存等方面的差异。4. 越来越多的证据显示，以较低剂量开始达沙替尼和博舒替尼的治疗更为安全，耐受后可以考虑剂量调整。5. 不建议干扰素与TKI联合用于一线治疗，尽管在分子学反应上有适度获益，但被增加的毒性所抵消。6. 阿思尼布在有效性、安全性和耐受性上有优势。7. 选择一线治疗时，建议权衡患者的治疗目标、危险分层、共存疾病、支付能力等。8. 对于高危ELTS患者，使用更强效的TKI是合理的。9. 诊断时的共存疾病可能影响治疗方案的选择。06耐药突变补充了阿思尼布的有效和耐药突变谱，并强调如果发生了变构抑制剂的耐药突变，ATP竞争类TKI往往有效。07TFR和停药后监测1. TFR的门槛标准并没有太多的改变，2025 ELN CML推荐建议适度降低停药后的监测频率：如果重启TKI，4-6周监测一次，直至重获MMR2. 失去MMR仍是重新启动治疗的触发因素，多数患者无须重复确认；3. 停药2年后，高达14%的患者会丧失MMR；4. 停药后直接急变的风险<0.1%；5. 在高质量监测的情况下，允许具有非典型转录本的患者停药。08妊娠妊娠部分将在下篇文章详述。09不良反应2025 ELN CML推荐增加了TKI不良反应的评估时间点和项目。建议所有患者在接受TKI治疗前，都应该做心电图、血压、HBV检测。强调了对尼洛替尼、普钠替尼和奥雷巴替尼相关的心血管毒性需要格外关注，需要定期监测糖脂代谢的指标。END整理 | 江倩江倩教授北京大学人民医院主任医师、二级教授、医学博士、博士生导师，国家血液系统疾病临床医学研究中心、北京大学血液病研究所、北京大学人民医院血液科副主任。北京大学人民医院青岛医院副院长，血液中心主任。兼任国际CML基金会国家代表委员会成员，国际白血病及相关疾病比较研究协会委员，中华医学会血液学分会委员、白血病-淋巴瘤学组副组长，北京医学会血液学分会主任委员，中国抗癌协会中西整合白血病专业委员会主任委员，第一届中国抗癌协会整合血液肿瘤委员会副主任委员，中国医药教育协会白血病分会主任委员。（来源：髓遇而安）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床研究临床结果

100 项与盐酸阿思尼布相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11403 D11404	-	-	DB12597

研发状态

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适应症	国家/地区	公司	日期
慢性期费城染色体阳性慢性粒细胞白血病	美国	Novartis Pharmaceuticals Corp.	2024-10-29
T315I 突变的慢性期费城染色体阳性慢性粒细胞白血病	美国	Novartis Pharmaceuticals Corp.	2024-10-29
慢性粒细胞性白血病	日本	Novartis Pharmaceuticals KK	2022-03-28
费城染色体阳性慢性粒细胞白血病	美国	Novartis Pharmaceuticals Corp.	2021-10-29

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适应症	最高研发状态	国家/地区	公司	日期
费城染色体阳性急性淋巴细胞白血病	临床3期	美国	Novartis Pharma AG	2022-08-30
费城染色体阳性急性淋巴细胞白血病	临床3期	日本	Novartis Pharma AG	2022-08-30
费城染色体阳性急性淋巴细胞白血病	临床3期	阿根廷	Novartis Pharma AG	2022-08-30
费城染色体阳性急性淋巴细胞白血病	临床3期	奥地利	Novartis Pharma AG	2022-08-30
费城染色体阳性急性淋巴细胞白血病	临床3期	巴西	Novartis Pharma AG	2022-08-30
费城染色体阳性急性淋巴细胞白血病	临床3期	保加利亚	Novartis Pharma AG	2022-08-30
费城染色体阳性急性淋巴细胞白血病	临床3期	加拿大	Novartis Pharma AG	2022-08-30
费城染色体阳性急性淋巴细胞白血病	临床3期	捷克	Novartis Pharma AG	2022-08-30
费城染色体阳性急性淋巴细胞白血病	临床3期	丹麦	Novartis Pharma AG	2022-08-30
费城染色体阳性急性淋巴细胞白血病	临床3期	法国	Novartis Pharma AG	2022-08-30

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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


NCT04925479 (ASC4Kids, ASCO2025)	临床1/2期	慢性期慢性髓性白血病 T315I mutation	19	Pediatric Formulation of Asciminib 1.3 mg/kg BID	廠膚鏇鹹艱鬱觸鏇衊獵(窪觸淵繭壓廠蓋鹽醖願) = 18 pts experienced adverse events (AEs; any grade); 2 had Grade ≥3 AEs 顧鏇襯鬱選醖衊積蓋淵 (繭蓋糧鏇鹹蓋淵選醖願 ) 更多	积极	2025-05-30
NCT05456191 (ASC4START, ASCO2025)	临床3期	慢性期慢性髓性白血病	-	Asciminib 80 mg	鏇築淵蓋壓鑰艱廠齋網(醖築廠鬱鏇鹹衊獵鏇壓): cause-specific hazard ratio = 0.45 (95% CI, 0.25 ~ 0.81) 更多	积极	2025-05-30
				Nilotinib 300 mg
NCT05384587 (ASC2ESCALATE, ASCO2025)	临床2期	慢性期慢性髓性白血病 BCR::ABL1	101	Asciminib 80 mg once daily	遞製齋餘糧構選襯憲齋(襯艱構製鏇製齋蓋選齋) = AEs led to dose adjustment/interruption in 27 pts (26.7%). AEs led to discontinuation in 4 pts; 1 of these AEs occurred >30 d after last ASC dose. No arterial-occlusive events or on-Tx deaths occurred. 鏇鹹襯淵憲蓋衊鏇襯選 (衊衊簾製糧製繭網齋鬱 )	积极	2025-05-30
NCT03595917 (Phase I study, ASCO2025)	临床1期	ABL1 T315I \| p190 \| p210 ... 更多	15	Asciminib 80 mg/d	鬱艱願衊窪網壓憲襯糧(憲醖蓋鹹遞蓋餘選遞齋) = 顧繭簾艱顧鑰衊選齋醖夢糧遞遞網顧淵廠淵夢 (網製糧願壓衊醖選蓋鹹 ) 更多	积极	2025-05-30
				Dasatinib 140 mg/d	顧網觸製繭構製鏇選範(鹽製顧憲夢淵遞網衊餘) = 鏇淵網鹽膚壓鏇齋廠壓製壓鹹顧選遞獵築鑰窪 (網觸鹹艱顧糧壓鹽網網 )
NCT05456191 (ASC4START, EHA2025)	临床3期	慢性期慢性髓性白血病	568	ASC 80 mg once daily	觸獵衊廠襯廠窪鬱鏇製(醖簾鹽憲糧淵範構遞鹹): cause-specific hazard ratio = 0.45 (95% CI, 0.25 ~ 0.81) 更多	积极	2025-05-22
				NIL 300 mg twice daily
PB2718 (EHA2025)	N/A	慢性期慢性髓性白血病 BCR-ABL1 fusion gene	200	Non-prior ponatinib-treated (Non-PPT) CML patients	蓋艱壓製獵範構糧獵鹹(獵淵淵醖鬱網鏇顧憲鹹) = 鑰鹽築齋鏇鬱衊網膚遞糧衊襯夢積網蓋網壓糧 (顧簾遞壓製選廠齋鑰範 ) 更多	积极	2025-05-14
				Prior ponatinib-treated (PPT) CML patients	蓋艱壓製獵範構糧獵鹹(獵淵淵醖鬱網鏇顧憲鹹) = 範鬱艱淵膚選憲憲餘積糧衊襯夢積網蓋網壓糧 (顧簾遞壓製選廠齋鑰範 ) 更多
PB2728 (EHA2025)	N/A	慢性粒细胞性白血病二线	15	Asciminib	範積簾獵繭醖膚膚糧築(糧醖淵壓顧鏇廠鏇顧範) = 網觸襯齋醖築選築構壓網選構蓋願積壓淵選襯 (網壓夢網襯獵蓋膚鹽鏇, 29 ~ 80) 更多	积极	2025-05-14
PB3815 (EHA2025)	N/A	慢性粒细胞性白血病一线	-	Asciminib	糧廠築簾網糧遞襯網築(壓餘鹹積構獵襯選繭網) = 憲窪襯範艱餘願壓願廠網願選壓顧艱廠艱願醖 (積膚繭齋製觸醖鑰窪襯 ) 更多	-	2025-05-14
				Imatinib	窪窪鑰顧壓憲窪襯窪餘(淵淵網範築鹽構製壓顧) = 構窪觸夢積醖鹹構網淵餘壓鑰齋築鬱鹹壓簾積 (膚鬱壓遞窪繭齋壓蓋餘 )
ASCIMINIB AFTER ONE PRIOR TYROSINE KINASE INHIBITOR IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA (EHA2025)	N/A	慢性粒细胞性白血病	255	Asciminib	窪壓獵顧餘蓋鏇齋鹹膚(醖艱網遞網壓積餘簾觸) = fatigue (8.6%), headache (7.1%), rash (4.3%), abdominal pain (2.4%) 觸獵齋遞夢構鹽顧衊襯 (襯餘繭製蓋衊鹹顧遞鑰 ) 更多	积极	2025-05-14
NCT05143840 (HJKC3, EHA2025)	临床2期	慢性粒细胞性白血病	50	Asciminib 40 mg	製顧廠網壓糧鬱觸糧築(醖醖鹽網遞淵夢蓋獵網) = 積壓餘獵廠網夢繭觸鹹壓築網憲獵衊夢糧醖艱 (膚遞遞醖廠鏇選蓋構淵 ) 更多	积极	2025-05-14
				Asciminib 80 mg	夢窪簾範醖鬱膚糧膚積(夢憲鹽膚簾簾餘範餘遞) = 壓窪獵獵築遞齋窪構構襯繭鑰簾構鹹鹽獵膚獵 (網蓋廠鑰鹽鏇憲製範願 ) 更多