主要研究目的：评估空腹和餐后状态下单次口服受试制剂泊那替尼片（规格：15 mg，持证商：成都硕德药业有限公司）与参比制剂泊那替尼片（Iclusig®，规格：15 mg，持证商：大塚製薬株式会社）在健康参与者体内的药代动力学参数，评价空腹和餐后状态下口服两种制剂的生物等效性。次要研究目的：评估泊那替尼片（规格：15 mg）与参比制剂泊那替尼片（Iclusig®，规格：15 mg）在健康参与者中的安全性。

开始日期2025-03-25

申办/合作机构

成都硕德药业有限公司

CTR20250810

/ Active, not recruitingN/A

评估受试制剂泊那替尼片与参比制剂泊那替尼片（ICLUSIG®）作用于健康成年受试者的单中心、开放、随机、单剂量、交叉生物等效性研究

研究空腹状态下单次口服受试制剂泊那替尼片与参比制剂泊那替尼片（ICLUSIG®）在健康成年受试者体内的药代动力学，评价空腹状态下口服两种制剂的生物等效性和安全性。

开始日期2025-03-20

申办/合作机构

齐鲁制药有限公司

100 项与盐酸普纳替尼相关的临床结果

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100 项与盐酸普纳替尼相关的转化医学

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100 项与盐酸普纳替尼相关的专利（医药）

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2,047

项与盐酸普纳替尼相关的文献（医药）

2025-12-31·Virulence

Ponatinib and other clinically approved inhibitors of Src and Rho-A kinases abrogate dengue virus serotype 2- induced endothelial permeability

Article

作者: Awasthi, Mansi ; Modak, Ayan ; Sobha, Archana ; Sreekumar, Easwaran ; Mishra, Srishti Rajkumar

Severe dengue often presents as shock syndrome with enhanced vascular permeability and plasma leakage into tissue spaces. In vitro studies have documented the role of Src family kinases (SFKs) and RhoA-kinases (ROCK) in dengue virus serotype 2 (DENV2)-induced endothelial permeability. Here, we show that the FDA-approved SFK inhibitors Bosutinib, Vandetanib and Ponatinib, as well as the ROCK inhibitors, Netarsudil and Ripasudil significantly inhibit DENV2-induced endothelial permeability. In cultured telomerase immortalized human microvascular endothelial cells (HMEC-1), treatment with these inhibitors reduced the phosphorylation of VE-Cadherin, Src and myosin light chain 2 (MLC2) proteins that were upregulated during DENV2 infection. It also prevented the loss of VE-Cadherin from the inter-endothelial cell junctions induced by viral infection. In in-vivo studies using DENV2-infected AG129 IFN receptor-α/β/γ deficient mice, ponatinib, when administered 24 h post-infection onwards, demonstrated significant benefits in improving body weight, clinical outcomes, and survival rates. While all virus-infected, untreated mice died by day-10 post-infection, 80% of the ponatinib-treated mice survived, and approximately 60% were still alive at the end of the 15-day observation period. The treatment also significantly reduced disease severity factors such as vascular leakage, thrombocytopenia; mRNA transcript levels of proinflammatory cytokines such as IL-1β and TNF-α; and restored liver function. Comparable effects were observed even when ponatinib treatment was initiated after symptom onset. The results highlight ponatinib as an effective therapeutic option in severe dengue; and also a similar potential for other FDA- approved SFK and ROCK inhibitors.

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

Treatment of Older Patients With ALL

Review

作者: Haddad, Fadi G. ; Jabbour, Elias ; Kantarjian, Hagop

Older patients with ALL often have high-risk disease characterized by adverse-risk cytogenetic and molecular abnormalities, as well as Philadelphia chromosome (Ph)-positive and Ph-like phenotypes. They often have comorbidities resulting in poor tolerance to chemotherapy and are at risk of developing therapy-related myeloid neoplasms (t-MNs). In Ph-negative ALL, the duration and intensity of chemotherapy was reduced, and outcomes improved with the addition of inotuzumab ozogamicin (InO) and blinatumomab into the frontline setting. However, t-MNs are still being observed, prompting the development of chemotherapy-free regimens with InO and blinatumomab as well as chimeric antigen receptor (CAR) T-cell therapies in high-risk disease. In Ph-positive ALL, chemotherapy and allogeneic hematopoietic stem-cell transplantation (HSCT) were historically considered a standard of care. However, the introduction of blinatumomab and newer-generation BCR::ABL1 tyrosine kinase inhibitors (TKIs) into the frontline setting significantly improved outcomes. The combination of blinatumomab and ponatinib induced high rates of complete molecular responses and excellent survival, without reliance on HSCT. A subset of patients with elevated WBC count at diagnosis are at particular risk of CNS and systemic relapse and may require additional strategies such as incorporating one to two cycles of high-dose methotrexate/cytarabine into consolidation, and potentially CAR T cells. In T-cell ALL, adding venetoclax into the frontline setting has improved outcomes. In early T-cell precursor ALL, HSCT is still needed. To further improve outcomes in older patients, novel agents such as subcutaneous blinatumomab, CAR T cells, newer-generation TKIs, and menin inhibitors should be investigated in the frontline setting.

2025-06-01·Toxicology reports

Gossypol enhances ponatinib's cytotoxicity against human hepatocellular carcinoma cells by involving cell cycle arrest, p-AKT/LC3II/p62, and Bcl2/caspase-3 pathways

Article

作者: Elkattan, Hadeel H ; El-Lakkany, Naglaa M ; Elsisi, Alaa E

Despite significant breakthroughs in frontline cancer research and chemotherapy for hepatocellular carcinoma (HCC), many of the suggested drugs have high toxic side effects and resistance, limiting their clinical utility. Exploring potential therapeutic targets or novel combinations with fewer side effects is therefore crucial in combating this dreadful disease. The current study aims to use a novel combination of ponatinib and gossypol against the HepG2 cell line. Cell survival, FGF19/FGFR4, apoptotic and autophagic cell death, and synergistic drug interactions were assessed in response to increasing concentrations of ponatinib and/or gossypol treatment. Research revealed that ponatinib (1.25-40 μM) and gossypol (2.5-80 μM) reduced the viability of HepG2 cells in a way that was dependent on both time and dose. Ponatinib's anti-proliferation effectiveness was improved synergistically by gossypol and was associated with a rise in apoptotic cell death, cell cycle blockage during the G0/G1 phase, and suppression of the FGF19/FGFR4 axis. Furthermore, the ponatinib/gossypol combination lowered Bcl-2 and p-Akt while increasing active caspase-3, Beclin-1, p62, and LC3II. This combination, however, had no harm on normal hepatocytes. Overall, gossypol enhanced ponatinib's anticancer effects in HCC cells. Notably, this new combination appears to be potential adjuvant targeted chemotherapy, a discovery that warrants more clinical investigation, in the management of patients with HCC.

243

项与盐酸普纳替尼相关的新闻（医药）

2025-06-12

·漫游药化

学懂通路第二期：生长因子与受体酪氨酸激酶 (RTKs）

导读上一期我们讲到RTKs的分类、结构功能，并以一个重要的家族—表皮生长因子受体（EGFR）家族RTK为例，阐述配体和受体的结合方式（学懂通路第一期）。本期我们对其他家族的RTKs进行概述。01血小板衍生生长因子 (PDGF) 受体及相关受体家族上图是血小板衍生生长因子（PDGF）受体家族配体与受体激活模式示意图。目前鉴定出能够激活PDGFR的配体主要有四种：PDGFA、PDGFB、PDGFC与PDGFD。它们通过二硫键形成具有活性的同源二聚体(AA, BB, CC、DD)以及异源二聚体（AB）。当二聚体配体与受体结合后，引起受体不同亚型（PDGFR-α, PDGFR-β）的二聚化（αα, ββ，αβ），进一步将信号传递到细胞内，引起胞内效应产生。研究发现，PDGF与肿瘤发生生长过程关系密切，尤其是能够促进肿瘤血管生成。PDGFR通路与另一种肿瘤血管生成有关的信号通路—VEGFR通路关系密切。涉及PDGFR的药物大多为双靶点或多靶点，例如Sunitinib、Axitinib、Cediranib 。此外，除了上述PDGF的受体（PDGFR-α, PDGFR-β）外，本家族还包括SCF、Flt-3LG 和M-CSF/IL-34的受体（参见上期表1）。注：SCF ：Stem Cell Factor干细胞因子，也称作：KITLG (即：KIT配体)；受体为：KIT/ SCFR；FLT3LG: FMSlike tyrosine kinase-3 ligand，FMS样酪氨酸激酶3配体；受体为 FLT3；MCSF: 巨噬细胞集落刺激因子（MCSF）和白介素- 34 (IL34) 受体均为 CSF1R；02血管内皮生长因子（VEGF）受体家族血管内表皮生长因子（VEGF）主要由VEGF-A、VEGF-B、VEGF-C、VEGF-D和胎盘生长因子PGF/PIGF 等5个成员组成（VEGF E和VEGF F是蛇毒来源，此处不作论述）。而血管内表皮生长因子受体（VEGFR）包括三种类型：VEGFR1, VEGFR2 及VEGFR3。VEGF与VEGFR的主要作用模式如上图所示。其中VEGFR-2主要表达在血管内皮细胞，是VEGF的主要受体，VEGFA/VEGFR-2是诱导血管生成的最主要通路。由于肿瘤细胞生长代谢旺盛，需要通过新生血管供应能量，因此靶向VEGF/VEGFR 通路是一种抑制肿瘤生长的思路。前面我们也提到，很多RTKs通路之间存在交叉，VEGFR也不例外。目前FDA批准的涉及VEGFR靶点的药物均为多靶点药物：分别为midostaurin（急性髓细胞性白血病、肥大细胞白血病）、lenvatinib（分化型甲状腺癌）、nintedanib（特发性肺纤维化）、axitinib（肾细胞癌）、regorafenib（结肠直肠癌、肺细胞癌、胃肠道间质瘤）、cabozantinib（肾细胞癌、肺细胞癌、髓甲状腺癌）、ponatinib（慢性粒细胞性白血病、急性淋巴细胞性白血病）、vandetanib（甲状腺癌）、pazopanib（肾细胞癌、软组织肉瘤）、sunitinib（肾细胞癌、胃肠道间质瘤、胰腺神经内分泌肿瘤）和sorafenib（甲状腺癌、肾细胞癌）。针对VEGF的单抗也已经批准上市，例如:贝伐珠单抗（Bevacizumab）能够高亲和力且特异性地结合VEGF，抑制肿瘤血管增生的作用，获批上市用于转移性结肠癌治疗。03胰岛素受体（INSR）家族胰岛素受体家族包括胰岛素受体( insulin receptor，INSR) ，胰岛素样生长因子受体( insulin-like growth factor receptor，IGFR)，胰岛素受体相关受体( insulin receptor-relatedreceptor，INSRR) 。胰岛素受体家族成员可以与各自的配体：胰岛素(Insulin，INS) 、胰岛素样生长因子( IGF-1或IGF-2)结合发挥激酶作用。配体INS、IGF1、IGF2与不同受体之间的作用模式图如上图所示。根据组织特异性，胰岛素受体（INSR）有A和B两种亚型，IGF-2和INS能够与许多上皮组织表达的INSR-A受体结合（诱导同源二聚化或与INSR-B异源二聚化)，促进细胞生长；而INSR-B是一种高度特异性的胰岛素受体，主要在INS敏感组织中表达，只有INS能够诱导INSR-B同源二聚体的产生，调节葡萄糖稳态。此外，IGF1和IGF2能够诱导IGF1R的同源二聚化，也可以诱导INSR（A或者B）与IGF1R的异源二聚化。写到这里肯定有读者要问：有没有IGF2R？其实是有的，但是IGF2R结合IGF2之后，并不能转录信号，反而引起通路抑制，因此我们这里就不提了。研究表明，INSR-A和IGF1R在肿瘤细胞高表达；PI3K途径（第四期介绍）是INS、IGF激活相应受体下游的主要通路。反之，IGF2R则表现出肿瘤抑制的功能。04成纤维细胞生长因子（FGF）及其受体成纤维细胞因子家族一共有18种细胞因子，而与之对应的是4种成纤维细胞因子受体（FGR1、FGR2、FGR3、FGR4）。FGF-FGFR的主要功能是将FGF信号转导到RAS-ERK和PI3K-AKT等途径的信号级联放大。FGR1、FGR2、FGR3都存在两种b、c亚型，在间质(结膜)组织或上皮组织表达。简易的作用模式图如上图，图中仅展示了7种FGF。FGFR的功能异常在多种肿瘤中发现，其中基因扩增、基因突变以及染色体重排是导致FGFR异常激活的主要原因。目前，单一针对FGFR的抑制剂很少，大多是多靶点抑制剂。05肝细胞生长因子(HGF)和c-MET受体肝细胞生长因子(HGF)主要通过细胞膜上的特异性受体c-MET发挥生物学作用。c-MET是原癌基因c-MET编码的具有自主磷酸化活性的跨膜受体，由50 KD的α亚基和145 KD的β亚基组成的异二聚体。HGF具有两个c-MET受体结合域，其前体经蛋白水解酶水解作用产生活性形式。成熟的HGF分子由分子量为96KD的α链和分子量为34KD的β链组成。HGF是由间质细胞分泌，但c-MET受体却主要在上皮细胞表达，故认为HGF是上皮-间质相互作用的介质。细胞癌变的一个典型标志是出现上皮-间质转化，而c-MET被认为在其中起到了关键驱动作用。研究发现，由于c-MET基因扩增、突变、染色体重排等导致c-MET在多种肿瘤中异常表达，而c-MET的不适当激活促进细胞增殖、细胞运动、侵袭性和血管生成，并与更具侵袭性的表型和较低的生存率相关。 06胶质细胞神经营养因子(GDNF)和RET受体胶质细胞神经营养因子（GDNF）家族包括 neurturin、persephin、artemin及 GDNF 四个成员。GDNF能够被胞外蛋白GFRα1/2/3/4特异性地结合,但由于GFRα1/2/3/4缺乏跨膜和胞内结构域，无法单独完成信号传导。因此，GFRα通过促进RET蛋白受体的磷酸化并使RET进入激活状态，激活下游通路。RET是由c-RET原癌基因编码的一种受体酪氨酸激酶，磷酸化的RET激活其下游的丝裂原活化蛋白激酶MAPK、P13激酶等，导致一系列胞内途径的激活，从而发挥GDNF家族神经营养因子的生理功能。RET的突变与II型多发性内分泌肿瘤相关，甲状腺髓样癌（MTC）中可观察到RET基因的突变，突变形式主要是点突变。总的来说，RET基因突变比较低频，主要的突变形式是与其他基因发生融合。07间变性淋巴瘤激酶受体（ALK）和白细胞受体酪氨酸激酶受体(LTK)ALK(间变性淋巴瘤激酶)和LTK(白细胞受体酪氨酸激酶)，最早是在淋巴瘤中被发现。在大部分正常细胞中ALK呈非活化状态，当ALK基因发生突变，常导致蛋白异常活化。ALK激活突变主要发生在神经母胶质瘤（neuroblastoma）中，在甲状腺癌、肺癌等肿瘤中也能检测到ALK激活型突变。由于没有鉴定出ALK的配体，长久以来ALK一直是一个孤儿受体（orphan receptor）（曾有研究人员鉴定出Pleiotrophin (PTN) 和Midkine (MK)可以与ALK结合，但是争议很大）。2015年1月，耶鲁大学医学院药理学系主任Joseph Schlessinger的研究团队在science发文称：herparin（肝素）是ALK真正的受体。目前已经上市的ALK 小分子抑制剂包括1代的克唑替尼（Crizotinib）；2代的塞瑞替尼（Ceritinib）、阿来替尼（Alectinib）、布加替尼（Brigatinib）；以及3代的劳拉替尼（Lorlatinib）。国产的2代药恩沙替尼（Ensartinib）也已经在去年上市。08血管生成素(ANG)和TIE受体血管生成通过人体中存在的诸多互补和复杂的信号途径调节的。其中主要的三条通路有：血管内皮生长因子 (VEGF)- 血管内皮生长因子受体 (VEGFR) 、血管生成素 (ANG)-TIE2 轴和 DLL4-Notch通路。ANG家族是唯一既含激动作用又含抑制作用的促血管生成因子，包含ANG1, 2 和 4三个成员，通过诱导内皮细胞上的酪氨酸激酶受体TIE-2同源二聚化，参与血管生成；同时，ANG-2也可以通过诱导TIE-1、TIE-2 异源二聚化，从而抑制血管生成。09肝配蛋白（Ephrins）及EPH受体促红细胞生成素产生肝细胞受体 (Eph)及其配体ephrins作为酪氨酸蛋白激酶受体家族最大的亚群，在细胞黏附、定位、迁移和分化过程中起关键作用。Ephrins可分为A、B两类，对应两类EPH受体，其相互作用模式目前还未完全研究清楚。EPH受体介导的分子内信号传递主要由细胞内酪氨酸激酶ABL及Rho GTP酶的鸟苷酸交换因子介导，对细胞的增值/迁徙产生激活或抑制作用。10神经营养酪氨酸激酶受体（NTRK）/ 原肌凝蛋白受体激酶(TRK )Tropomyosin receptor kinase （原肌球蛋白受体激酶，TRK ），也称作Neurotrophin receptor kinase（神经营养受体酪氨酸激酶，NTRK），是一类受体酪氨酸激酶家族，包括分别由NTRK1、NTRK 2和NTRK3基因编码的TrkA、TrkB和TrkC三种受体。在健康组织中，NTRK与神经生长因子（NGF）等配体组成的通路参与神经系统的发育和功能以及细胞存活，在健康组织中起重要的作用。在某些情况下，NTRK 基因与一个不相关的基因融合，导致 Trk 信号不受控制地激活，从而导致癌症发生。在常见的癌症如肺癌，乳腺癌，结直肠癌中，只有1%~5%的患者存在NTRK 基因融合，而一些罕见的癌症，比如婴儿纤维肉瘤和分泌型乳腺癌，存在NTRK融合的频率却高达90%~100%。针对NTRK融合突变上市的药物及在研的药物临床效果显著，因此NTRK也称为“钻石”基因。目前，全球上市的用于治疗NTRK融合基因实体瘤的药物有两个，分别是拜耳/LOXO的拉罗替尼（2018年11月被FDA批准上市）以及罗氏的恩曲替尼（2019年8月被FDA批准上市）。11TAM受体 TAM受体包括三个成员，即：TYRO3、AXL和MERTK受体。与之对应的是两个配体：GAS6和PROS1。该受体家族的基因最初从白血病细胞中克隆出来的，并被认为是原癌基因，其表达水平与实体肿瘤，尤其是胶质母细胞瘤的恶性程度有关，但未发现基因突变或重排。12盘状结构域受体（DDR受体）盘状结构域受体（discoidindomain receptors, DDRs）是一种受体型蛋白酪氨酸激酶，包括 DDR1 和 DDR2，该类蛋白的胞外结构域上含有一个类似于盘基网柄菌凝集素盘状结构域 1的结构，也称盘状结构域（DR 区）；其次，在 DR 区与跨膜区之间有很长的近膜区（JM区）。 DDRs 在人和小鼠组织中表达广泛，能与多种胶原蛋白特异性结合并被激活,参与多种疾病过程,如肿瘤、炎性反应和纤维化的发生发展。13受体酪氨酸激酶样孤儿受体（ROR）受体酪氨酸激酶样孤儿受体（ROR）家族包括ROR1、ROR2两个受体，与核受体中的ROR家族不同，ROR是一类膜受体，由于ROR蛋白最初发现时配体未知，所以被定义为孤儿受体。有研究表明：ROR1通过识别WNT蛋白介导的非经典WNT信号通路传递，在多种生理过程中发挥重要作用，包括调节细胞分裂、增殖、迁移和细胞趋化等。14ROS 受体ROS受体是由原癌基因c-ROS编码的受体酪氨酸激酶，其配体未知。ROS基因重排在胶质母细胞瘤、非小细胞肺癌等多个恶性肿瘤中发现，导致激酶持续激活，上调多种下游信号通路，导致细胞持续增殖生。此外，ROS基因还与多个基因发生融合突变。参考文献：[1] Robert, Jacques. Textbook of Cell Signalling in Cancer [M]. Springer International Publishing, 2015.[2] Wagener C , Stocking C , O. Müller. Cancer Signaling - From Molecular Biology to Targeted Therapy[M]. 2017.[3] Amanda H . Cancer cell signalling[M]. Wiley Blackwell, 2014.部分信息图片来源于网络，侵权联系后台删除。下期预告第三期：MAPK通路；第三期：PI3K通路；感谢支持，欢迎“分享”和“点赞”

临床2期临床终止

2025-05-18

·药明康德

有望2-3个月给药一次的哮喘疗法；疾病控制率超90%的ADC…… | 一周盘点

本期看点1. 抗体偶联药物（ADC）CX-2051在晚期结直肠癌（CRC）中取得了积极的1期临床试验结果，总缓解率（ORR）为28%，疾病控制率（DCR）达94%。2. IL-4Rα靶向单抗APG808在治疗哮喘的1b期临床试验中表现亮眼，该疗法在12周内对一种与哮喘恶化相关的2型炎症生物标志物具有强效且持续的抑制作用，有望支持其实现每两个月或更长时间一次的给药方案。3. FDA批准了Lantern Pharma公司的新型“合成致死”小分子药物LP-184的IND申请。CX-2051：公布1期临床试验的中期数据CytomX Therapeutics公布了其ADC疗法CX-2051在晚期结直肠癌（CRC）中的积极1期中期数据。CX-2051是一种条件激活型ADC，其使用的细胞毒性有效载荷是喜树碱的衍生物。喜树碱是一种拓扑异构酶-1抑制剂，这类药物已在ADC领域针对多个靶点显示出强大的临床抗癌活性。CX-2051已在包括结直肠癌在内的多个临床前模型中显示出强大的临床前活性和耐受性。截至2025年4月7日的数据，ORR为28%（5/18），其中10 mg/kg剂量组的ORR达到43%（3/7），显著高于目前三线及三线以上结直肠癌治疗药物的缓解率（通常仅有个位数的百分比）。DCR为94%（17/18），中位无进展生存期为5.8个月。截至数据截止时，18名患者中有10名仍在接受治疗。安全性方面，CX-2051的耐受性良好，未出现剂量限制性毒性（DLT），大多数治疗相关不良事件为1级或2级。APG808：公布1b期临床试验的中期数据Apogee Therapeutics公司公布了其候选单抗APG808用于治疗轻度至中度哮喘患者的1b期临床试验的积极中期数据。APG808是一种新型、皮下注射、半衰期延长的IL-4Rα靶向单抗，具有用于治疗哮喘、慢性阻塞性肺病（COPD）及其他炎症与免疫学适应症的潜力。IL-4Rα是一个已在八种2型过敏性疾病中得到临床验证的靶点。在1期临床试验中，APG808的药代动力学（PK）特征有望支持每2-3个月一次的维持治疗给药方案。此次公布的结果显示，多剂量给药APG808可使FeNO（一种与哮喘恶化相关的2型炎症生物标志物）较基线大幅下降53%，并在12周时仍维持约50%的抑制水平，显示出对哮喘的持续控制能力。APG808的优化配方和潜在“best-in-class”的PK特征，结合在12周内对FeNO的强效且持续的抑制作用，有望支持其实现每两个月或更长时间一次的给药方案，相较于目前每两周一次的标准治疗具有优势。此外，APG808整体耐受性良好，安全性特征与已有的抗IL-4Rα疗法一致。Soquelitinib：公布1期临床试验中队列1-3的数据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，所有3个队列中，soquelitinib治疗组在具有临床意义的终点湿疹面积和严重度指数较基线减少75%（EASI 75）和研究者总体评估（IGA）评分为0/1（皮肤症状清除或几乎清除）上，均显示出相较于安慰剂的显著疗效。与队列1和队列2（100 mg每天两次和200 mg每天一次，每日总剂量200 mg）相比，队列3（200 mg每天两次，每日总剂量400 mg）的缓解更早且更深。安全性方面，soquelitinib的耐受性良好，在所有队列中均未观察到DLT，也未出现具有临床意义的实验室指标异常。此外，所有队列中均未发生中断给药的情况。▲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[1]）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1月21日的数据，在36例可评估的患者中，44%（16/36）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40%（10/25）达到了MMR，曾接受asciminib或ponatinib治疗的患者中也有36%（9/25）达到MMR，包括1例携带已知asciminib耐药突变的患者。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在所有剂量组中仍表现出良好的耐受性，与其选择性激酶谱一致。LP-184：IND申请获得FDA许可Lantern Pharma公司宣布，FDA已批准其抗癌新药LP-184的IND申请。LP-184将与免疫检查点抑制剂联用，针对携带KEAP1和/或STK11突变和PD-L1低表达的非小细胞肺癌（NSCLC）患者开展1b/2期临床试验。LP-184是一种新型“合成致死”小分子药物，其作用机制是在前列腺素还原酶1（PTGR1）的激活下诱导DNA双链断裂。PTGR1在KEAP1突变型肿瘤中显著过表达。临床前研究表明，LP-184对NSCLC细胞系的杀伤力与PTGR1的表达水平呈正相关。该公司专有的RADR平台驱动的计算机分析和临床前研究表明，LP-184对DNA损伤修复（DDR）缺陷型癌症特别有效，包括携带KEAP1和STK11突变的NSCLC。此外，PTGR1会在肿瘤细胞内将LP-184由前药转化为具有生物活性的细胞毒性物质，而正常组织由于PTGR1表达水平低，基本不受影响。这使得LP-184有望在具有强效抗肿瘤活性的同时降低全身毒性。值得注意的是，LP-184的作用机制不受TP53突变状态影响。该突变是导致当前多种疗法产生耐药性的常见共突变因素。参考资料（可上下滑动查看）[1] Corvus Pharmaceuticals Announces Data from Cohorts 1-3 of Placebo-Controlled Phase 1 Clinical Trial of Soquelitinib for Atopic Dermatitis. Retrieved May 16, 2025, from https://investor.corvuspharma.com/news-releases/news-release-details/corvus-pharmaceuticals-announces-data-cohorts-1-3-placebo[2] MaaT Pharma Announces Promising Final Data Readout for Phase 1b Evaluating MaaT033 in Amyotrophic Lateral Sclerosis (ALS). Retrieved May 16, 2025, from https://www.businesswire.com/news/home/20250511855391/en/MaaT-Pharma-Announces-Promising-Final-Data-Readout-for-Phase-1b-Evaluating-MaaT033-in-Amyotrophic-Lateral-Sclerosis-ALS[3] Cantargia announces successful Phase 1 results: PK/PD data of subcutaneously administered CAN10 confirms every 4-week dosing choice in Phase 2. Retrieved May 16, 2025, from https://cantargia.com/en/press-releases/cantargia-announces-successful-phase-1-results-pk-pd-data-of-subcutaneously-administered-can10-confirms-every-4-week-dosing-choice-in-phase-2[4] Apogee Therapeutics Announces Positive Interim Results from the Phase 1b Trial of APG808, its Novel Half-life Extended IL-4Rα Antibody, in Patients with Mild-to-Moderate Asthma. Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/12/3078912/0/en/Apogee-Therapeutics-Announces-Positive-Interim-Results-from-the-Phase-1b-Trial-of-APG808-its-Novel-Half-life-Extended-IL-4R%CE%B1-Antibody-in-Patients-with-Mild-to-Moderate-Asthma.html[5] CytomX Announces Positive Interim Data From Phase 1 Dose Escalation Study of EpCAM Antibody Drug Conjugate (CX-2051) Candidate in Patients with Advanced Colorectal Cancer (CRC). Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/12/3078935/37704/en/CytomX-Announces-Positive-Interim-Data-From-Phase-1-Dose-Escalation-Study-of-EpCAM-Antibody-Drug-Conjugate-CX-2051-Candidate-in-Patients-with-Advanced-Colorectal-Cancer-CRC.html[6] MavriX Bio Announces FDA Clearance of IND Application to Initiate First-in-Human Study of Gene Therapy for Angelman Syndrome. Retrieved May 16, 2025, from https://www.prnewswire.com/news-releases/mavrix-bio-announces-fda-clearance-of-ind-application-to-initiate-first-in-human-study-of-gene-therapy-for-angelman-syndrome-302451763.html[7] Ensoma Announces FDA Clearance of IND Application for First In Vivo HSC-Directed Gene Insertion Therapy. Retrieved May 16, 2025, from https://ensoma.com/press-release/ensoma-announces-fda-clearance-of-ind-application-for-first-in-vivo-hsc-directed-gene-insertion-therapy/[8] Faron Pharmaceuticals presents promising Phase 1/2 data from BEXMAB Study at MDS 2025 plenary session. Retrieved May 16, 2025, from https://faron.com/releases-and-publications/faron-pharmaceuticals-presents-promising-phase-1-2-data-from-bexmab-study-at-mds-2025-plenary-session/[9] Lantern Pharma Secures FDA Clearance for Planned Phase 1b/2 Trial of LP-184 in Biomarker-Defined, Treatment-Resistant NSCLC Patients with High Unmet Clinical Need. Retrieved May 16, 2025, from https://ir.lanternpharma.com/news-events/press-releases/detail/179/lantern-pharma-secures-fda-clearance-for-planned-phase-1b2[10] Innovo Therapeutics Announces Positive Phase 1 Results for INV-101, a Novel Immuno-Metabolic Modulator for Autoimmune Diseases. Retrieved May 16, 2025, from https://www.businesswire.com/news/home/20250512131551/en/Innovo-Therapeutics-Announces-Positive-Phase-1-Results-for-INV-101-a-Novel-Immuno-Metabolic-Modulator-for-Autoimmune-Diseases[11] Capsida Receives FDA IND Clearance for Its First-in-Class, IV-administered Gene Therapy for STXBP1 Developmental and Epileptic Encephalopathy. Retrieved May 16, 2025, from https://capsida.com/capsida-receives-fda-ind-clearance-for-its-first-in-class-iv-administered-gene-therapy-for-stxbp1-developmental-and-epileptic-encephalopathy/[12] AAVantgarde presents positive clinical data from its AAVB-081 program for Usher 1B and preclinical data from its AAVB-039 program for Stargardt at the ARVO 2025 annual meeting. Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/12/3078987/0/en/AAVantgarde-presents-positive-clinical-data-from-its-AAVB-081-program-for-Usher-1B-and-preclinical-data-from-its-AAVB-039-program-for-Stargardt-at-the-ARVO-2025-annual-meeting.html[13] Artiva Biotherapeutics Announces Longer-term Phase 1/2 Data Demonstrating Prolonged Durability for AlloNK® in Combination with Rituximab in Patients with B-cell-Non-Hodgkin Lymphoma at the ASGCT 28th Annual Meeting. Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/13/3080625/0/en/Artiva-Biotherapeutics-Announces-Longer-term-Phase-1-2-Data-Demonstrating-Prolonged-Durability-for-AlloNK-in-Combination-with-Rituximab-in-Patients-with-B-cell-Non-Hodgkin-Lymphoma.html[14] Sernova Biotherapeutics Provides Positive Interim Data from Ongoing Phase 1/2 Clinical Trial of Cell Pouch Bio-hybrid Organ in Patients Living with Type 1 Diabetes. Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/14/3080975/0/en/Sernova-Biotherapeutics-Provides-Positive-Interim-Data-from-Ongoing-Phase-1-2-Clinical-Trial-of-Cell-Pouch-Bio-hybrid-Organ-in-Patients-Living-with-Type-1-Diabetes.html[15] Enliven Therapeutics Announces Updated Positive Data from Phase 1 Clinical Trial of ELVN-001 in CML and Oral Presentation at the EHA 2025 Congress. Retrieved May 16, 2025, from https://www.prnewswire.com/news-releases/enliven-therapeutics-announces-updated-positive-data-from-phase-1-clinical-trial-of-elvn-001-in-cml-and-oral-presentation-at-the-eha-2025-congress-302455412.html[16] AbCellera Receives Authorization from Health Canada to Initiate the Phase 1 Clinical Trial of ABCL635 for Vasomotor Symptoms Due to Menopause. Retrieved May 16, 2025, from https://investors.abcellera.com/news/news-releases/2025/AbCellera-Receives-Authorization-from-Health-Canada-to-Initiate-the-Phase-1-Clinical-Trial-of-ABCL635-for-Vasomotor-Symptoms-Due-to-Menopause/default.aspx[17] Biomea Fusion’s BMF-500 Selected for Poster Presentation at EHA 2025 Highlighting Phase I Data in Relapsed/Refractory Acute Leukemia. Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/14/3081603/0/en/Biomea-Fusion-s-BMF-500-Selected-for-Poster-Presentation-at-EHA-2025-Highlighting-Phase-I-Data-in-Relapsed-Refractory-Acute-Leukemia.html[18] Athira Pharma to Present Data from First-in-Human Phase 1 Clinical Trial of ATH-1105 at the 4th Annual ALS Drug Development Summit. Retrieved May 16, 2025, from https://investors.athira.com/news-releases/news-release-details/athira-pharma-present-data-first-human-phase-1-clinical-trial[19] Rocket Pharmaceuticals Presents Preliminary Data from Phase 1 Clinical Trial of RP-A601 for PKP2 Arrhythmogenic Cardiomyopathy at 28th Annual Meeting of the American Society of Gene and Cell Therapy. Retrieved May 16, 2025, from https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-presents-preliminary-data-phase-1[20] START Doses First U.S. Patient in Moderna's Phase 1 Clinical Trial of mRNA-4106, a Pan-Tumor Antigen Therapy Candidate, in Solid Tumors. Retrieved May 16, 2025, from https://www.prnewswire.com/news-releases/start-doses-first-us-patient-in-modernas-phase-1-clinical-trial-of-mrna-4106-a-pan-tumor-antigen-therapy-candidate-in-solid-tumors-302455728.html[21] Pasithea Therapeutics Announces Initiation of Phase 1/1B Study of PAS-004 in Adult NF1 Patients and Activation of First Clinical Trial Site. Retrieved May 16, 2025, from https://ir.pasithea.com/news-events/press-releases/detail/120/pasithea-therapeutics-announces-initiation-of-phase-11b免责声明：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1期临床结果抗体药物偶联物临床2期临床申请

2025-05-14

·Business Wire

Kesmalea Therapeutics Appoints Industry Veteran Tim Clackson to Board of Directors

LONDON--(BUSINESS WIRE)--Kesmalea Therapeutics, a biopharmaceutical company developing a pipeline of novel therapeutics founded on the ability to transform large heterobifunctional protein degraders into small molecules, today announced the appointment of senior life sciences executive Dr. Tim Clackson to its Board of Directors. Dr. Clackson brings to Kesmalea more than three decades of experience building oncology companies, including leading the R&D behind three approved drugs. He most recently served as Chief Executive Officer of Boston-based IDRx, Inc., a precision oncology therapy developer which was acquired by GSK in 2025 for up to $1.15 billion. “Kesmalea’s science represents a highly innovative, modular and scalable solution to unlock the full potential of targeted protein degradation,” said Dr. Clackson. “Kesmalea’s science represents a highly innovative, modular and scalable solution to unlock the full potential of targeted protein degradation,” said Dr. Clackson. “I look forward to working with their impressive team and the Board to help bring SELFTAC technology to the clinic and maximize its value.” “Targeted protein degradation holds enormous promise for medicine, but its most prominent drug class, PROTACs, faces innate issues caused by molecular size and structure. As we work to solve these challenges with our unique approach, we're assembling a world-class team to bring our mission to life," said Clive Dix, Chairman of the Kesmalea Board. "We're delighted to welcome Tim to the Board - his impressive track record of discovering and developing high impact targeted therapies for a range of cancer types will be invaluable as we translate our drug discovery research into revolutionary new medicines.” As IDRx CEO, Dr. Clackson led a team developing a best-in-class targeted therapy for gastrointestinal stroma tumor (GIST), through clinical proof-of-concept, a Series B financing and the acquisition by GSK. Prior to IDRx, Dr. Clackson was President and CEO of Theseus Pharmaceuticals, a clinical stage biotechnology company focused on development of targeted oncology therapies, where he led the Company through its initial public offering and early clinical development for its lead product candidate for GIST and other targeted therapies in its pipeline. Prior to Theseus, he served as President at Xilio Therapeutics, a privately held oncology company developing tumor-selective immunotherapies, where he led the development of the company’s technology and product strategy. From 1994 to 2018, Dr. Clackson was with ARIAD Pharmaceuticals, serving as President of R&D and Chief Scientific Officer from 2010. He played a key role in the company’s evolution from early research to a global commercial oncology company, and its subsequent acquisition by Takeda for $5.2 billion. Dr. Clackson led the multi-disciplinary R&D team that internally discovered and developed five clinical-stage product candidates, including ICLUSIG® (ponatinib), approved for patients with treatment-resistant Ph+ leukemias; ALUNBRIG® (brigatinib), approved for ALK+ non-small cell lung cancer (NSCLC); and EXKIVITY™, approved for Exon20 insertion+ NSCLC. Dr. Clackson received his B.A. in Biochemistry from the University of Oxford, his Ph.D. in Biology from the University of Cambridge, and completed a postdoctoral fellowship at Genentech. He serves as a Director on the Board of Elevation Oncology and previously served as a Director on the Boards of Forma Therapeutics (acquired by Novo Nordisk), Spring Bank Pharmaceuticals, and the Massachusetts Biotechnology Council (MassBio). About Kesmalea Therapeutics Kesmalea is developing a pipeline of novel therapeutics founded on the ability to transform large protein degraders into small molecules. This is achieved through SELFTAC®, a platform designed to combine the power of protein degradation with small molecule advantages such as oral bioavailability and central nervous system (CNS) penetration, among others. Kesmalea’s current research spans targets in oncology and diseases of the CNS, with broader applicability. The company is built on foundational scientific work by founder & CSO Harry Finch, Ph.D., a noted medicinal chemist and entrepreneur. Kesmalea has offices and labs in London, UK. Kesmalea's £25m Series A was led by Syncona Ltd alongside Oxford Science Enterprises. For more information, please visit: www.kesmalea.com.

高管变更上市批准并购免疫疗法

100 项与盐酸普纳替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09951	盐酸普纳替尼	L01XE24	DB08901

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
慢性粒细胞性白血病	澳大利亚	Takeda Pharmaceuticals Australia Pty Ltd.	2014-11-26
加速期慢性骨髄性白血病	欧盟	Incyte Biosciences Distribution BV	2013-07-01
加速期慢性骨髄性白血病	冰岛	Incyte Biosciences Distribution BV	2013-07-01
加速期慢性骨髄性白血病	列支敦士登	Incyte Biosciences Distribution BV	2013-07-01
加速期慢性骨髄性白血病	挪威	Incyte Biosciences Distribution BV	2013-07-01
急性转化期慢性粒细胞性白血病	欧盟	Incyte Biosciences Distribution BV	2013-07-01
急性转化期慢性粒细胞性白血病	冰岛	Incyte Biosciences Distribution BV	2013-07-01
急性转化期慢性粒细胞性白血病	列支敦士登	Incyte Biosciences Distribution BV	2013-07-01
急性转化期慢性粒细胞性白血病	挪威	Incyte Biosciences Distribution BV	2013-07-01
慢性期慢性髓性白血病	欧盟	Incyte Biosciences Distribution BV	2013-07-01
慢性期慢性髓性白血病	冰岛	Incyte Biosciences Distribution BV	2013-07-01
慢性期慢性髓性白血病	列支敦士登	Incyte Biosciences Distribution BV	2013-07-01
慢性期慢性髓性白血病	挪威	Incyte Biosciences Distribution BV	2013-07-01
费城染色体阳性急性淋巴细胞白血病	欧盟	Incyte Biosciences Distribution BV	2013-07-01
费城染色体阳性急性淋巴细胞白血病	冰岛	Incyte Biosciences Distribution BV	2013-07-01
费城染色体阳性急性淋巴细胞白血病	列支敦士登	Incyte Biosciences Distribution BV	2013-07-01
费城染色体阳性急性淋巴细胞白血病	挪威	Incyte Biosciences Distribution BV	2013-07-01
急性淋巴细胞白血病	美国	Takeda Pharmaceuticals U.S.A., Inc.	2012-12-14
费城染色体阳性慢性粒细胞白血病	美国	Takeda Pharmaceuticals U.S.A., Inc.	2012-12-14

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适应症	最高研发状态	国家/地区	公司	日期
费城染色体阳性成人前体急性淋巴细胞白血病	临床2期	美国	Takeda Pharmaceutical Co., Ltd.	2024-01-01
费城染色体阳性白血病	临床2期	美国	Takeda Pharmaceutical Co., Ltd.	2021-02-24
费城染色体阳性白血病	临床2期	中国	Takeda Pharmaceutical Co., Ltd.	2021-02-24
费城染色体阳性白血病	临床2期	阿根廷	Takeda Pharmaceutical Co., Ltd.	2021-02-24
费城染色体阳性白血病	临床2期	澳大利亚	Takeda Pharmaceutical Co., Ltd.	2021-02-24
费城染色体阳性白血病	临床2期	巴西	Takeda Pharmaceutical Co., Ltd.	2021-02-24
费城染色体阳性白血病	临床2期	捷克	Takeda Pharmaceutical Co., Ltd.	2021-02-24
费城染色体阳性白血病	临床2期	法国	Takeda Pharmaceutical Co., Ltd.	2021-02-24
费城染色体阳性白血病	临床2期	意大利	Takeda Pharmaceutical Co., Ltd.	2021-02-24
费城染色体阳性白血病	临床2期	墨西哥	Takeda Pharmaceutical Co., Ltd.	2021-02-24

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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


ASCO2025	N/A	费城染色体阳性急性淋巴细胞白血病	338	Ponatinib and Blinatumomab Combination Therapy	築顧願餘醖淵鏇蓋廠鬱(夢醖糧廠鏇夢鬱艱糧顧) = 獵鹽醖襯顧壓醖齋獵壓廠廠選遞餘齋餘遞鏇餘 (遞範鏇鏇衊鑰繭築廠蓋, 0.751 ~ 0.930)	积极	2025-05-30
ASCO2025	N/A	急性淋巴细胞白血病	583	Ponatinib	遞蓋鏇選網鹽簾淵壓膚(艱鹹觸鑰網繭鹹顧醖齋) = 窪構願鑰鹽鹽齋齋鹽糧願衊蓋簾廠構繭醖齋簾 (遞糧艱壓齋窪憲願糧壓 ) 更多	积极	2025-05-30
				Imatinib	鬱餘艱願鏇鬱簾艱鏇構(鹽簾鬱簾積範衊築範鏇) = 積範蓋鏇繭膚獵壓齋顧顧選糧襯鏇襯齋積夢憲 (壓簾艱簾壓憲鹽積觸積 )
NCT03263572 (Pubmed \| J Hematol Oncol)	临床2期	费城染色体阳性急性淋巴细胞白血病 \| 难治性成人急性淋巴细胞白血病 \| 加速期慢性骨髄性白血病 ... CD19 expression \| VPREB1 deletion 更多	76	Blinatumomab and Ponatinib	鏇獵餘襯鑰鬱鏇艱餘醖(夢構遞積遞鹹鑰窪築製) = 膚構遞選繭遞夢膚醖鹹夢襯糧窪構遞艱餘襯構 (繭蓋窪鏇簾夢獵繭製餘 ) 更多	积极	2025-05-14
NCT03589326 (ponatinib‐3001, Pubmed \| Cancer Med)	临床3期	费城染色体阳性急性淋巴细胞白血病	-	Ponatinib	顧構醖艱鏇廠鬱淵齋鑰(壓構鑰夢窪廠衊餘鏇憲) = 憲艱鏇範衊觸築憲簾鏇鏇選範繭蓋獵醖顧願觸 (齋遞選憲遞顧範觸艱餘 ) 更多	积极	2025-04-01
NCT02272998 (CTgov)	临床2期	晚期恶性实体瘤 \| 晚期癌症	22	laboratory biomarker analysis+ponatinib hydrochloride	製簾顧憲窪窪築艱範襯 = 鏇醖襯簾衊鏇積積襯窪淵壓糧遞顧鹹艱選簾淵 (顧遞壓鏇鹽衊願鏇夢鹹, 齋顧夢壓淵鏇廠製遞構 ~ 醖鬱簾襯餘齋蓋壓窪積) 更多	-	2025-03-24
ASH2024	N/A	费城染色体阳性慢性粒细胞白血病	-	Ponatinib-based therapy	糧鬱願憲廠艱遞網顧範(膚糧餘糧願鹽鬱積餘願) = 醖廠遞醖窪鬱繭顧憲範糧蓋淵範範鏇願鏇壓窪 (淵膚醖鏇廠膚觸艱鏇網 ) 更多	-	2024-12-08
				Intensive chemotherapy (IC)	艱顧鏇構築鏇構糧壓齋(廠醖鬱餘範蓋醖觸顧廠) = 齋鬱壓網鑰範顧齋夢夢製鹹範淵遞廠選淵獵壓 (鏇壓艱糧鏇餘願願壓廠 )
ASH2024	N/A	费城染色体阳性急性淋巴细胞白血病	-	Ponatinib	醖襯衊鏇窪簾顧鏇獵膚(鑰鏇壓齋糧夢艱顧簾衊) = Vascular occlusive events (peripheral arterial occlusive disease and venous thrombosis; both grade 2) occurred in 2/34 pts receiving ponatinib monotherapy; both events resolved following dose reduction or interruption. 餘構築網夢範積鹽鏇醖 (齋願積鬱艱遞顧遞廠糧 )	-	2024-12-08
				Imatinib
ASH2024	N/A	费城染色体阳性急性淋巴细胞白血病	-	Ponatinib	憲鹹獵繭餘築壓齋廠壓(鹽鏇蓋觸淵夢齋艱廠網) = 餘夢構構製鏇夢餘構鏇膚簾鑰鬱糧繭醖廠遞醖 (襯憲淵憲糧鹹築淵艱構 ) 更多	-	2024-12-08
				Imatinib	憲鹹獵繭餘築壓齋廠壓(鹽鏇蓋觸淵夢齋艱廠網) = 齋觸獵壓簾糧築憲淵鏇膚簾鑰鬱糧繭醖廠遞醖 (襯憲淵憲糧鹹築淵艱構 )
NCT04070443 (TIPI, ASH2024)	临床2期	费城染色体阳性慢性粒细胞白血病	-	Ponatinib 30 mg QD	顧選鏇壓齋糧蓋範獵願(餘齋膚齋顧遞範網積顧) = 2 hematologic (grade 4 neutropenia at M6) 餘鏇鏇膚顧襯夢鹽鹽範 (壓築範衊選觸遞鹹選衊 )	积极	2024-12-08
				Imatinib 400 mg QD
ASH2024	N/A	费城染色体阳性慢性粒细胞白血病	-	Ponatinib 45 mg	鹹鏇夢艱衊鏇選繭選鹽(餘齋齋願蓋膚鏇獵蓋憲) = Thirty-one pts had ≥1 PON-related AE, most commonly hypertension (n=4), increased lipase, increased alanine aminotransferase, and increased aspartate aminotransferase (n=2 each). Six pts had CV events, including 1 arterial occlusion event. 憲製觸齋願選鹹網窪齋 (鹽鏇網顧製糧鏇積範積 )	-	2024-12-07
				Ponatinib 30 mg