A Randomized International Phase 3 Trial of Imatinib and Chemotherapy With or Without Blinatumomab in Patients With Newly-Diagnosed Philadelphia Chromosome-Positive or Philadelphia Chromosome-Like ABL-Class B-Cell Acute Lymphoblastic Leukemia

This phase III trial compares the effect of the combination of blinatumomab with dasatinib and standard chemotherapy versus dasatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (PH+) or Philadelphia chromosome-like (Ph-Like) ABL-class B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib in combination with standard chemotherapy may work better in treating patients with PH+ or Ph-Like ABL-class B-ALL compared to dasatinib and chemotherapy alone.

开始日期2025-02-28

申办/合作机构

National Cancer Institute

100 项与 c-Kit x Bcr-Abl 相关的临床结果

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100 项与 c-Kit x Bcr-Abl 相关的转化医学

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0 项与 c-Kit x Bcr-Abl 相关的专利（医药）

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项与 c-Kit x Bcr-Abl 相关的文献（医药）

2024-08-21·Cureus

Chronic Myeloid Leukemia Unveils Its Dark Side: A Rare Case of Megakaryocytic Blast Crisis

Article

作者: Poombal, Fnu ; Poombal, FNU ; Suhail, Maymoona ; Faisal, Alizah ; Khalid, Mehreen ; Muhammad Asad Khan, Fatima

Chronic myeloid leukemia (CML) can progress from a chronic phase (CP) to an accelerated phase (AP) or an acute leukemia-like blastic phase (BP). However, transformation into a megakaryoblastic phase is very rare, and such a progression is clinically significant due to its poor prognosis and resistance to standard tyrosine kinase inhibitors (TKIs). This report discusses a case of CML that progressed to a megakaryoblastic phase and the patient's death within a month despite receiving one cycle of daunorubicin, cytarabine, and TKI chemotherapy. A 39-year-old female with CML (CP) initially achieved hematological remission with nilotinib but later presented with B symptoms and cytopenias indicative of disease progression. A complete diagnostic workup was performed, including blood counts, bone marrow examination, flow cytometry, fluorescence in-situ hybridization (FISH), and cytogenetic testing. Peripheral blood and bone marrow evaluation confirmed blast crisis with 84% medium to large-sized blasts with basophilic cytoplasm and cytoplasmic blebs. The blasts were positive for CD41 and CD61 by immunohistochemistry (IHC). The blasts also expressed CD45 (dim), CD34, CD33, CD117, CD41, and CD61 by flow cytometry. While BCR-ABL1 positivity is typically associated with CML (90-95%), the additional findings point towards a transformation to acute megakaryoblastic leukemia (AMKL or AML-M7). The rare instance of CML's transformation to AMKL highlights the need for megakaryocytic markers in diagnostic panels to ensure accurate diagnosis and timely, tailored therapies for improved outcomes.

2024-05-01·Indian Dermatology Online Journal

Imatinib- and Nilotinib-Induced Lichenoid Eruption in Chronic Myeloid Leukemia: A Rare Case Report

Article

作者: Gupta, Aanchal ; Singh, Jayanti ; Dayal, Surabhi ; Sachdeva, Meenakshi

AbstractImatinib and nilotinib are inhibitors of tyrosine kinases (TKIs) generated from the bcr-abl fusion protein, c-Kit, and platelet-derived growth factor receptors. Cutaneous adverse effects (AEs) of TKI are the most frequent non-hematological sequelae. In our case, the common molecular target raises the possibility that cross-intolerance, in which similar AEs occur with both agents, can arise. We hereby report a rare case report on cross-intolerance of cutaneous AEs of imatinib and nilotinib in chronic myeloid leukemia.

2023-09-01·Clinical laboratory

Complex Karyotype Acute Basophilic Leukemia with Reactive Mast Cell Hyperplasia.

作者: Li, Ruimin ; Wu, Yiping ; Zhang, Xiaofang ; Guo, Hongxia ; Guo, Jia

BACKGROUNDThe goal of the study is to improve the understanding of complex karyotype acute basophilic leukemia with reactive mast cell hyperplasia.METHODSA case of clinical and laboratory characteristics of complex karyotype acute basophilic leukemia with reactive mast cell hyperplasia and review of related literature of patient with acute basophilic leukemia were retrospectively analyzed.RESULTSLaboratory tests: alanine aminotransferase 225 U/L, aspartate aminotransferase 129 U/L, total protein 3.0 g/L, albumin 25.0 g/L, globulin 17.8 g/L, total bilirubin 183.9 μmol/L, indirect bilirubin 65.6 μmol/L, D-dimer 13.02 mg/L, prothrombin time 19.30 S, white blood cell 37.30 x 109/L, red blood cells 2.06 x 1012/L, hemoglobin 71 g/L, platelets 13 x 109/L, and basophilic granulocyte cells 5.01 x 109/L. Bone marrow smear: a large number of abnormal primitive cells were scattered and distributed. The characteristics of these cells were as follows: the cell body size was different, most of them were round or quasi-round, the cytoplasm volume was medium, and the cytoplasm was stained gray blue. The cytoplasmic processes were visible, and basophilic particles were visible in part of the cytoplasm and/or on the nucleus. The nuclei were mostly round or almost round, with distortion and folding. The chromatin was detailed, the nucleoli varied in number, and some nucleoli were deeply stained. The cells showed double and multiple nuclei, scattered and occasionally small clumps. Bone marrow biopsy: acute myeloid leukemia, not excluding basophilic leukemia. Bone marrow molecular biology: All 29 myeloid leukemia genes, including RARA and BCR-ABL fusion genes, were negative. Flow cytometry results showed abnormal cell population which accounted for 21.98% of nuclear cells. The phenotypes are CD33++, CD38+, CD13+, CD123+, CD7+, CD36+, CD203c+, CD81+, part of CD34+, part of HLA-DR+, CD4 weak+, weak CD117+, the TDT-, cCD3-, cCD79a-, MPO-, CD11c-, CD25-, CD2-. In addition, mast cells accounted for 1.15% of nuclear cells, expressing CD203c, but not CD25 and CD2. Karyotype analysis results were 46, XY, -7, psudic (9; 19) (p24; p13.3), add (15) (p12), add (21) (q22), +r, +1 - 2 mar [cp20].CONCLUSIONSAcute basophilic leukemia (ABL) is a rare malignant hematologic tumor. Bone marrow smears, biopsies, flow cytometry, and cytogenetic tests play an important role in the diagnosis and differentiation of complex karyotype acute basophilic leukemia with reactive mast cell hyperplasia.

项与 c-Kit x Bcr-Abl 相关的新闻（医药）

2024-07-04

·PRNewswire

Ascentage Pharma Received US$100 Million Option Payment from Takeda

ROCKVILLE, Md. and SUZHOU, China, July 3, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing and commercializing both first-in-class and best-in-class therapies for hematological malignancies, announced today that on July 2, 2024, in relation to the Exclusive Option Agreement with Takeda for the third-generation BCR-ABL inhibitor olverembatinib (HQP1351), Ascentage Pharma has received the US$100 million option payment called for by the Exclusive Option Agreement. On June 14, 2024, Ascentage Pharma and Takeda entered into an Exclusive Option Agreement that granted Takeda an exclusive option to enter into an exclusive license agreement for olverembatinib. The Exclusive Option Agreement calls for Ascentage Pharma to receive an option payment of US$100 million and provides for Ascentage Pharma to be eligible for an option exercise fee and additional potential milestone payments of up to approximately US$1.2 billion and double-digit royalties on annual sales. About Ascentage Pharma Ascentage Pharma (6855.HK) is a fully integrated global biopharmaceutical company engaged in discovering, developing and commercializing both first-in-class and best-in-class therapies to address global unmet medical needs primarily in hematological malignancies. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. Ascentage Pharma has built a pipeline of 9 clinical-stage drug candidates, including novel, highly potent Bcl-2, and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation TKIs. Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 40 clinical trials, including 6 global registrational Phase III studies, in the US, Australia, Europe, and China. Olverembatinib, the company's first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted Orphan Drug Designations (ODDs) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer Center, National Cancer Institute and the University of Michigan. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions and expectations or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions and expectations may alter in light of future development. SOURCE Ascentage Pharma

快速通道临床3期孤儿药引进/卖出突破性疗法

2024-06-12

·医药观澜

亚盛医药「奥雷巴替尼」新适应症获批注册性3期临床

6月11日，亚盛医药宣布奥雷巴替尼的新适应症临床试验申请获得中国国家药监局药品审评中心（CDE）批准，该公司将开展一项全球注册3期临床研究，评估奥雷巴替尼治疗系统性全身治疗失败的琥珀酸脱氢酶（SDH）缺陷型胃肠间质瘤（GIST）患者的效果。奥雷巴替尼是亚盛医药开发的一款口服第三代BCR-ABL抑制剂，目前已有两项适应症获批上市，分别为：1）治疗任何TKI耐药、并伴有T315I突变的慢性髓细胞白血病（CML）慢性期（-CP）和加速期（-AP）的成年患者；2）治疗对一代和二代TKI耐药和/或不耐受的CML-CP成年患者。奥雷巴替尼在中国的商业化推广由亚盛医药和信达生物共同负责。本次获得CDE批准的是一项全球多中心、单臂、开放性关键注册3期临床试验，旨在评估奥雷巴替尼在SDH缺陷型GIST患者中的有效性和安全性。根据亚盛医药新闻稿，CDE已同意该项临床试验的研究结果用于支持未来SDH缺陷型GIST适应症的上市申请。 GIST是消化道最常见的软组织肉瘤。KIT和PDGFRA是GIST主要的致癌驱动基因，其中85%～90%的GIST患者有KIT或PDGFRA突变。酪氨酸激酶抑制剂（TKI）的出现改善了这类GIST患者的预后。尽管如此，仍有约85%的儿童GIST和10%~15%的成人GIST患者并不携带KIT或PDGFRA突变，称为野生型GIST。根据SDH表达是否缺失，野生型GIST可分为SDH缺陷型GIST和非SDH缺陷型GIST。SDH缺陷型GIST患者发病年轻，严重影响生存质量，且生存期明显缩短，患者亟需新的治疗手段。针对SDH缺陷型GIST患者，此前奥雷巴替尼已被CDE纳入突破性治疗品种。在今年的美国临床肿瘤学会（ASCO）年会上，研究人员还以口头报告形式展示了奥雷巴替尼在TKI耐药的SDH缺陷型GIST患者中的最新数据。这是一项1期临床研究，共计入组了26例SDH缺陷型GIST患者。数据显示，6例患者获部分缓解（PR），另有18例患者疾病稳定（SD）且持续时间超过4个周期，患者的临床获益率（CBR）达92.3%（24/26），中位无进展生存期（PFS）为25.7个月。安全性方面，患者的不良反应情况与之前报道的相同，治疗期间未发现新的安全性问题。参考资料： [1]中国国家药监局药品审评中心（CDE）官网. Retrieved June 11, 2024, from https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d [2] 【直击ASCO 2024】奥雷巴替尼在SDH缺陷型GIST患者中临床获益率达92.3%，口头报告最新进展. Retrieved June 05 , 2024, from https://mp.weixin.qq.com/s/Mwt58HxD083fltosZgs_RQ 内容来源于网络，如有侵权，请联系删除。

ASCO会议临床结果申请上市

2024-06-11

·BioBAY

重大里程碑！亚盛医药耐立克®这项三期研究获CDE临床许可！

BioBAY园内企业亚盛医药今日宣布，公司原创1类新药奥雷巴替尼（获国家药品监督管理局（NMPA）药物审评中心（CDE）临床试验许可，将开展其针对系统性全身治疗失败的琥珀酸脱氢酶（succinate dehydrogenase, SDH）缺陷型胃肠间质瘤（gastrointestinal stromal tumor, GIST）患者的全球注册III期临床研究。这是亚盛医药在实体瘤领域临床开发的重大里程碑。该研究是一项全球多中心、单臂、开放性关键注册III期临床试验，旨在评估耐立克®在SDH缺陷型GIST患者中的有效性和安全性。CDE已同意该项临床试验的研究结果将支持未来SDH缺陷型GIST适应症的上市申请。 GIST是消化道最常见的软组织肉瘤，全球发病率约每年1/10万-1.5/10万 1。KIT及PDGFRA是GIST主要的致癌驱动基因，其中85%～90%的GIST患者有KIT或PDGFRA突变。酪氨酸激酶抑制剂（TKI）的出现，改善了这类GIST患者的预后。尽管如此，仍有约85%的儿童GIST和10%-15的成人GIST患者并不携带KIT或PDGFRA突变，称为野生型GIST。根据SDH表达是否缺失，野生型GIST可分为SDH缺陷型GIST和非SDH缺陷型GIST 2-3。 SDH缺陷型GIST具有独特的临床病理特征。文献报告中位诊断年龄为21岁，女性多见，好发部位为胃部，容易转移，免疫组化表现为SDHB蛋白表达缺失。早期局限型患者可通过手术治疗，但大部分患者仍会复发。复发和晚期的SDH缺陷型GIST患者目前无标准治疗方案，一般认为伊马替尼治疗无效，其他TKI的疗效也难以令人满意2-5，5年无事件生存（EFS）率仅为24% 4。SDH缺陷型GIST患者发病年轻，严重影响生存质量，且明显缩短生存期，这一存在紧迫未满足临床需求的领域亟需新的治疗手段。耐立克®是亚盛医药原创1类新药，为口服第三代TKI。此前，该品种已获CDE纳入突破性治疗品种，治疗既往经过一线治疗的SDH缺陷型GIST患者。作为多靶点TKI，耐立克®在SDH缺陷型GIST患者中展现出了显著的疗效和良好的安全性。其治疗SDH缺陷型GIST患者的临床研究自2022年起，已连续三年入选美国临床肿瘤学会（ASCO）年会，并在本月举办的第60届ASCO年会上口头报告了最新进展。数据表明，该品种在SDH缺陷型GIST患者中的临床获益率（CBR）高达92.3%。耐立克®是中国首个上市的第三代BCR-ABL抑制剂，目前已有两项适应症获批，分别为治疗任何TKI耐药、并伴有T315I突变的慢性髓细胞白血病（CML）慢性期（-CP）和加速期（-AP）的成年患者；和治疗对一代和二代TKI耐药和/或不耐受的CML-CP成年患者。耐立克®在中国的商业化推广由亚盛医药和信达生物共同负责。亚盛医药首席医学官翟一帆博士表示：“在前期研究中，耐立克®已经在SDH缺陷型GIST患者的治疗中展现出令人振奋的有效性和安全性。此次全球注册III期临床的获批让我们深受鼓舞！这不仅意味着耐立克®有望为又一个无药可医的适应症带来治疗突破，更是亚盛医药在实体瘤领域临床开发的重大里程碑。未来，我们将秉承‘解决中国乃至全球患者尚未满足的临床需求'这一使命，积极推进相关临床试验的开展，以造福更多患者。” ▌文章来源：亚盛医药责编：赵家帅审核：任旭推荐阅读上市企业丨康宁杰瑞：超6亿美元！与ArriVent就ADC产品研发和商业化达成合作上市企业丨基石药业：国产PD-L1出海重大里程碑！欧盟人用药品委员会推荐批准「舒格利单抗」用于一线治疗非小细胞肺癌上市企业丨创胜集团于ASCO首次公布Osemitamab (TST001)三联疗法一线治疗胃或胃食管结合部腺癌的II期临床数据

ASCO会议临床3期申请上市临床结果