A Phase 1 Open-Label Dose-Escalation Study of the Safety of Adoptively Transferred Autologous CD8+ T Lymphocytes Targeting HPV-16 E6/E7, HPV-18 E6/E7 and Survivin in Patients With Relapsed or Refractory HPV-related Oropharyngeal Cancers

This is a multicenter, open-label, Phase I, first-in-human trial to characterize the safety and clinical activity of an antigen-specific CD8+ T-cell product in patients with relapsed or refractory locally advanced or metastatic HPV-related oropharyngeal cancers. Patients must have received at least one prior standard treatment regimen consisting of systemic immunotherapy and/or chemotherapy. The investigative agent is an autologous adoptive T-cell product derived from the patient's endogenous cytolytic T cells that are directed toward HPV-16 E6/E7, HPV-18 E6/E7 antigens, and a tumor-associated antigen (Survivin) by ex vivo exposure to an artificial antigen presenting cell to which HLA-A2 antigen-peptides have been fit within the pocket of an MHC class 1 molecule. Patients must express HLA-A*0201.

开始日期2025-03-31

申办/合作机构

NexImmune, Inc.

NCT06377228 / Not yet recruiting临床1期

A Phase 1b, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of TAK-007, an Allogeneic Anti-CD19 Chimeric Antigen Receptor Natural Killer Cell (CD19 CAR-NK) Therapy, in Adult Subjects With Refractory Lupus Nephritis

The main aim of the study is to learn how well adults with refractory lupus nephritis (LN) tolerate TAK-007 and to check for side effects (adverse events).
Other aims are to learn how effective treatment with TAK-007 is in adults with refractory LN, what effects TAK-007 has on the human body, and whether participants will produce antibodies against TAK-007.

开始日期2024-11-01

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT06358430 / Not yet recruiting临床1期

Phase 1 Dose Escalation and Expansion Study of TROP2 CAR Engineered IL-15- Transduced Cord Blood-derived NK Cells in Combination With Cetuximab in Patient With Colorectal Cancer (CRC) With Minimal Residual Disease (MRD)

To find the highest and/or recommended dose of TROP2-CAR-NK cells combined with cetuximab in participants with MRD CRC.

开始日期2024-10-31

申办/合作机构

Bellicum Pharmaceuticals, Inc.

100 项与磷酸氟达拉滨相关的临床结果

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100 项与磷酸氟达拉滨相关的转化医学

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100 项与磷酸氟达拉滨相关的专利（医药）

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7,585

项与磷酸氟达拉滨相关的文献（医药）

2024-03-15·Journal of Computational Chemistry

Development of CHARMM compatible force field parameters and molecular dynamics simulations for the pesticide flupyradifurone

Article

作者: Thany, Steeve H ; Le Questel, Jean-Yves ; Bouchouireb, Zakaria

Abstract:

Flupyradifurone (FLU) is a novel butenolide insecticide with partial agonist activity for insect nicotinic acetylcholine receptors. Its safety for non‐target organisms has been questioned in the literature, despite initial claims of its harmlessness. Detailed understanding of its toxicity and related molecular mechanisms remain under discussion. Thus, in this work, an optimized set of CHARMM compatible parameters for FLU is presented. CHARMM General Force Field program was used as a starting point while the non‐bonded and bonded parameters were adjusted and optimized to reproduce MP2/6‐31G(d) accuracy level results. For the validity assessment of these parameters, infrared spectrum, water‐octanol partition coefficient, and normal modes were computed and compared to experimental values found in the literature. Several MD simulations of FLU in water and FLU in complex with an acetylcholine‐binding protein were performed to estimate the ability of the optimized parameters to correctly describe its torsional space and reproduce observed crystallographic trends respectively.

2024-03-01·Journal of Global Antimicrobial Resistance

Analysis of the relationship between drug susceptibility of Cryptococcus neoformans isolates and mortality in HIV-negative cryptococcal meningitis

Article

作者: Xu, Zirong ; Peng, Fuhua ; Yuan, Dasen ; Jiang, Ying ; Wei, Hang ; Li, Chongwen ; Su, Zhihui ; Dai, Kai ; Liu, Jia

OBJECTIVES:

The relationship between antifungal susceptibility and mortality of cryptococcal meningitis (CM) in HIV-negative patients is poorly understood.

METHODS:

We conducted a retrospective analysis of 1-year follow-up of 200 HIV-negative CM patients with an initial cerebrospinal fluid (CSF) culture for Cryptococcus neoformans. According to the cut-off values of minimum inhibitory concentration (MIC), two groups of five antifungal agents were classified: amphotericin B (AmB), ≤0.5 µg/mL, >0.5 µg/mL; 5-flucytosine (5-FC), ≤4 µg/mL, >4 µg/mL; fluconazole (FLU), ≤4 µg/mL, >4 µg/mL; itraconazole (ITR), ≤0.125 µg/mL, >0.125 µg/mL; and voriconazole (VOR), <0.25 µg/mL, ≥0.25 µg/mL. Comparisons were performed to analyse clinical features, laboratory, modified Rankin Scale (mRS) scores, and CSF findings under different prognosis outcomes in 1-year.

RESULTS:

All of Cryptococcus neoformans isolates were sensitive to AmB and VOR, most of them were sensitive to 5-FC and FLU (95.5% and 90.5%, respectively) while only 55.0% of them were susceptible to ITR. Minimum inhibitory concentrations of ITR and VOR were significantly related to baseline mRS scores. All-cause mortality was not significantly related to MICs in Cryptococcus neoformans strains. The combination of actual antifungal agents and two groups of the MICs values for antifungal agents had no significant effects on all-cause mortality.

CONCLUSION:

Most Cryptococcus neoformans isolates were sensitive to AmB, VOR, 5-FC, and FLU. Because of the small number of deaths, we are not able to comment on whether MIC is associated with mortality of CM in HIV-negative patients.

2024-03-01·Aquatic Toxicology

Combined toxicity of trifloxystrobin and fluopyram to zebrafish embryos and the effect on bone development

Article

作者: Yuan, Jie ; Guo, Yuzhao ; Zhang, Jie ; Miao, Weiguo ; Li, Qing X ; Fan, Yongmei ; Zhang, Taiyu ; Wang, Xinyu ; Xie, Jia

Trifloxystrobin (TRI) is a methacrylate fungicide, and fluopyram (FLU) is a new pyridylethylbenzamide fungicide and nematicide. Both are often detected in water bodies and may be highly toxic to many aquatic organisms. Unfortunately, the aquatic biological risks of single FLU or a mixture of trifloxystrobin and fluopyram have not been reported. In this study, zebrafish was selected as the test organism to investigate the combined toxicity of trifloxystrobin and fluopyram to zebrafish. After zebrafish embryos exposed to three pesticide solutions, Alcian-blue staining, Alizarin-red staining and quantitative PCR (qPCR) were performed. The results indicated that 96h-LC₅₀ of TRI was 0.159 mg·L^-1 to zebrafish embryo, which was highly toxic. The 96h-LC₅₀ of FLU to zebrafish embryos was 4.375 mg·L^-1, being moderately toxic. The joint toxicity to zebrafish embryos(FLU at 96h-LC₅₀ and TRI at 96h-LC₅₀ in a 1:1 weight ratio to form a series of concentration treatment groups) was antagonistic. Both trifloxystrobin and fluopyram also inhibited the skeletal development of zebrafish and showed to be antagonistic. The results of qPCR indicated upregulations of different genes upon three different treatments. TRI mainly induced Smads up-expression, which may affect the BMP-smads pathway. FLU mainly induced an up-expression of extracellular BMP ligands and type I receptor (Bmpr-1a), which may affect the BMP ligand receptor pathway. The 1:1 mixture (weight ratio) of trifloxystrobin and fluopyram induced a reduction of the genes of extracellular BMP ligand (Smads) and type I receptor (Bmpr1ba), which may down-regulate BMP signaling and thus attenuating cartilage hyperproliferation, hypertrophy and mineralization. The results warren an interest in further studying the effect of the two fungicides in a mixture on zebrafish.

301

项与磷酸氟达拉滨相关的新闻（医药）

2024-04-25

·今日头条

Nature：脐血来源CAR-NK细胞立大功，暴击B细胞恶性肿瘤

近年来，脐带血（CB/UCB）衍生细胞疗法在肿瘤学治疗领域取得了多项突破性进展，可作为提取NK细胞、T细胞、树突状细胞等的资源平台。与成人外周血相比，脐带血中造血干细胞（HSC）和祖细胞比例较高，免疫耐受性较强，增殖能力较强，而且NK细胞百分比较高，CB衍生的NK细胞已被证明是同种异体NK细胞输注、CAR-NK细胞等的重要来源。世界权威期刊《nature medicine（自然医学）》近期报道了MD安德森癌症中心（MDACC）进行的一项“ 脐带血来源的CAR-NK细胞，治疗复发或难治性B细胞恶性肿瘤 ”Ⅰ/Ⅱ期临床试验（NCT03056339）振奋人心的结果。 ▲截图源自“nature medicine” B细胞恶性肿瘤“克星”：脐血来源CAR-NK细胞，总生存率达68% ▲图源“frontiers”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除注：脐带血（CB）衍生细胞疗法概述安德森癌症中心进行的这项Ⅰ/Ⅱ期临床研究（NCT03056339），共入组37例患复发或难治性B细胞恶性肿瘤 [包括低度非霍奇金淋巴瘤（NHL）、未转化的慢性淋巴细胞白血病（CLL）、弥漫性大B细胞淋巴瘤（DLBCL） ]的患者，年龄为7-80岁。结果显示； 1、客观缓解率（OR）：37名患者治疗第100天的OR达48.6% 。值得注意的是，不同类型的癌种治疗30天后，客观缓解率有所差异。其中，低度NHL的OR率为100% ，未转化的CLL的OR率为67% ， DLBCL的OR率为41% 。 2、完全缓解（CR）率：37名患者治疗第30天、100天、1年的CR率分别为27%、29.7%、37.8% 。此外，研究人员还观察到 CAR-NK细胞治疗的持久反应。治疗1年后， 83%的低度NHL患者、50%的CLL患者、29%的DLBCL患者出现完全缓解。 3、生存率：治疗1年后，37例患者的总生存（OS）率为68% ，无进展生存率（PFS）为32% （详见下图）。 ▲图源“nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除如何寻求CAR-NK疗法帮助？目前正有多款研发的CAR-NK疗法，正在招募急性髓系白血病、复发或难治性多发性骨髓瘤、非小细胞肺癌、肾细胞癌等患者，想要参加的癌友可将近期病理报告、治疗经历等资料，提交至全球肿瘤医生网医学部进行初步评估，或了解详细的入排标准。杀伤力倍增的CAR-NK细胞，剑指多款血液肿瘤自然杀伤（NK）细胞是公认的人体第一道抗癌防线，不仅能识别癌细胞，而且无需提前激活，就可发挥杀伤肿瘤的能力。近年来，研究人员对NK细胞进行改造，相当于给NK细胞安装上一个“CAR导航头” ，使其拥有独特的靶细胞识别机制，以便精准锁定特定的抗原蛋白，让狡猾的癌细胞“无处隐藏”；同时又能保留NK细胞原有的肿瘤杀伤能力。 CAR-NK细胞设计之初主要用于对抗淋巴瘤、骨髓瘤、白血病等多种血液恶性肿瘤。与同样具有“血液肿瘤克星”的CAR-T细胞疗法相比，CAR-NK细胞无需与患者进行匹配，也就是说它的制备省去了从患者身上抽取T细胞，再进行体外扩增的这一复杂且费钱的过程，具有治疗时间更短、价格更低廉等优势，患者接受度更高。除了上文提到的脐血来源的CAR-NK细胞外，还有多项关于CAR-NK细胞在治疗血液肿瘤方面表现出卓越优势的临床研究，下面全球肿瘤医生网小编帮大家简单盘点一下，以供参考。 NKX101直击复发或难治性急性髓系白血病，CR率达50% 复发性或难治性（r/r）急性髓系白血病（AML）的既往治疗选择有限，靶向治疗往往只能使一小部分人群受益。近期，世界知名血液科杂志《Blood》报道了“ NKX101联合氟达拉滨（Fludarabine）和阿糖胞苷（Ara-C），治疗急性髓系白血病 ”令人惊艳的1期研究结果。 NKX101是一种源自健康供体的NK细胞疗法，经过改造可表达NKG2D配体导向的嵌合抗原受体（CAR），以增强对恶性肿瘤细胞的杀伤作用。本次入组的6例复发性或难治性急性髓系白血病（r/r AML）患者，既往接受过至少一种治疗，入组接受淋巴细胞清除（LD）+NKX101治疗后，结果显示： 1、完全缓解（CR）：6例患者中有3例达到CR（完全缓解率达50% ）。其中，1例患者在接受巩固性造血细胞移植（HCT）后，目前仍处于完全缓解（CR）状态；另1例患者在接受巩固治疗周期后，保持CR状态。 2、 CR/CRi ：4例达到“完全缓解”或“完全缓解但计数不完全恢复”（CR/CRi）。第3名患者接受了三个周期的治疗，疾病负担连续下降，并仍处于CRi状态。 3、 MRD ：3例患者通过血流检测，未检测到微小残留病灶（MRD）。 ▲图源“ASH”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除注：PK分析显示，NKX101与输注天数相关。 NKX019：重击B细胞恶性肿瘤，完全缓解率高达70%！ NKX019是一款冷冻保存的同种异体CAR-NK细胞疗法，可增强CD19靶向的人源化CAR的内在抗肿瘤活性，从而用于B细胞恶性肿瘤的治疗。 NKX019的1期临床试验数据（NCT05020678），在2023年血液学协会（EHA）大会上公布。本次研究共入组19例复发或难治性（r/r）B细胞恶性肿瘤患者，包括 5例白血病患者 [ 急性淋巴细胞白血病（ALL）、慢性淋巴细胞白血病（CLL） ]、 14例非霍奇金淋巴瘤患者 [ 滤泡性淋巴瘤(FL)、大B细胞淋巴瘤(LBCL)、边缘区淋巴瘤(MZL)/套细胞淋巴瘤(MCL) ]。这些患者ECOG体能状态为0或1，既往都接受过≥2种治疗。入组后，先后接受淋巴细胞清除（环磷酰胺+氟达拉滨）治疗、NKX019治疗。结果显示，在10例可评估疗效的患者中，总体缓解率达80% ，其中完全缓解（CR）率为70% （详见下图）。值得一提的是，大B细胞淋巴瘤（LBCL）患者的 CR率达到50% 。 ▲图源“WILEYOnline Library”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除这项突破性研究表明， NKX019在多种NHL组织学中均具有活性，而且安全性可控！ · CAR-NK治疗血液肿瘤的其他临床研究 · 全球肿瘤医生网小编汇总了，目前在研的治疗血液肿瘤的几款CAR-NK细胞疗法，详情参考下表。 ▲数据源自“中国生物制药有限公司”，全球肿瘤医讯编辑整理小编寄语抗击血液肿瘤的明星产品——CAR-T细胞疗法我们并不陌生，随着细胞免疫疗法的不断发展，科学家尝试将NK细胞与CAR工程融合，并期待二者能碰撞出神奇的“火花”。改造后的CAR-NK细胞具有先天抗肿瘤能力、同种异体来源、降低GVHD（移植物抗宿主反应）风险等独特优势，使其成为抗击癌症的多功能工具。随着越来越多的免疫细胞疗法从实验室走入临床，癌症治疗将逐渐进入“精准治疗时代”，小编也期望未来能有更多的技术与CAR工程完美结合，以突破癌症治疗瓶颈，让更多深受癌症折磨的病友获益！参考资料 [1]Marin D,et al.Safety,efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors:a phase 1/2 trial[J].Nature Medicine,2024: 1-13. https://www.nature.com/articles/s41591-023-02785-8 [2]Wang J,et al.Umbilical cord blood derived cellular therapy: advances in clinical development[J]. Frontiers in Oncology,2023,13:1167266. https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1167266/full [3]Sauter C S,et al.A Phase 1 Study of NKX101, a Chimeric Antigen Receptor Natural Killer (CAR-NK) Cell Therapy, with Fludarabine and Cytarabine in Patients with Acute Myeloid Leukemia[J].Blood,2023,142:2097. https://ash.confex.com/ash/2023/webprogram/Paper173582.html [4]Dickinson M,et al.First in human data of NKX019, an allogeneic CAR NK for the treatment of relapsed/refractory (R/R) B-cell malignancies[J].Hematol Oncol,2023,41(S2):526-527. https://onlinelibrary.wiley.com/doi/full/10.1002/hon.3164_389 [5]https://www.news-medical.net/whitepaper/20231113/CAR-NK-The-Next-Generation-in-Hematological-Malignancy-Treatment.aspx

细胞疗法免疫疗法临床结果

2024-04-22

·药时代

百亿大关已破！13款FDA批准的ADC，依次交上成绩单

2022年，全球ADC药物销售额突破了70亿美元。2023年，这一数字突破百亿大关，高达102亿美元！据文献预测: 2026 年，ADC 药物的销售额将超 164 亿美元！与化疗药物相比，ADC具有耐受性好、靶标识别准确、对非癌细胞的副作用小等优点，在治疗领域中占据着越来越重要的地位。目前，有13种ADC已被美国食品和药物管理局（FDA）批准，还有超过100种ADC处于不同的临床试验阶段。下面我们就来看看这13款ADC各有什么故事1Gemtuzumab ozogamicin（GO）公司：辉瑞意义：第一个获得全球市场批准的ADC适应症：AML（急性髓性白血病）结构：靶向CD33的人源化单抗+一种细胞毒性N-乙酰-γ-calicheamicin，通过可切割的肼键来连接。作用机制：GO与CD33抗原结合，形成GO-CD33复合物，然后被内吞到AML细胞中。在三个早期临床试验都产生积极结果之后，FDA在2000年批准了GO，特别是用于60岁以上的cd33阳性AML患者的治疗（图二）。图一：GO治疗的细胞作用机理2然而，GO在西南癌症研究集团（SWOG）S0106研究中爆出了安全性问题。该研究旨在评估GO在60岁以下AML成年患者中的疗效。该研究显示，与对照组相比，GO组的细胞致死性诱导率更高（5.5% vs. 1.4%）。与GO治疗相关的作用还包括骨髓抑制、输注反应、感染、出血和肝毒性等等。因此，辉瑞在2010年6月从市场上撤回了该产品。然而，数据表明，与对照组相比，GO对不适合强化化疗的老年AML患者的预后有良好的改善。毒性是可控的。基于这些研究，FDA在2017年又重新批准了GO。后续的研究显示，当GO联合fludarabine、cytarabine、粒细胞集落刺激因子和idarubicin使用时，和单独使用的效果一样，都能减缓疾病进展，尤其在cd33阳性AML患者的初诊中，GO是安全、有效和可行的。2Brentuximab vedotin (BV)公司：Seagen公司，后来与武田公司共同开发，意义：是第二种已获批准的ADC药物。适应症：霍奇金淋巴瘤（HL）和间变性大细胞淋巴瘤（ALCL）结构：布伦妥昔单抗（一种靶向CD30的IgG1嵌合单抗）、马来酰亚胺连接部分（一种可切割的二肽连接，mc-VC-PABC）和单甲基auristatin E（MMAE）。作用机理：BV特异性靶向在中表达的CD30抗原。成绩：2019年，BV在美国和加拿大市场销售额达到6.28亿美元，其他市场销售额达527亿日元，2022年销售额达到14.69亿美元，2023年销售额进一步增加至16.5亿美元。预计2026年BV的全球销售额将达到18亿美元在一项评估BV治疗HL和ALCL的有效性和安全性的I期研究中，大多数副作用事件均为1级和II级，常见的副作用包括疲劳、发烧、腹泻、恶心、中性粒细胞减少等。在一项II期临床试验中，BV分别在75%和87%的HL患者（102例患者）和ALCL患者（30例患者）中显示了有效性。此外，BV还可以缓解淋巴瘤引起的瘙痒和疼痛，而对患者的生活质量没有负面影响。2018年，FDA批准了BV联合CHP（即环磷酰胺、阿霉素和泼尼松）治疗初次用药的系统性ALCL患者或其他表达cd30抗原的成年患者。3Trastuzumab emtansine (T-DM1)公司：Genentech and ImmunoGen结构：通过硫醚连接剂将药物trastuzumab与emtansine（也称为DM1）连接而形成。适应症：HER2阳性癌症患者作用机理：trastuzumab选择性地将高活性的细胞毒性小分子药物DM1转运到HER2过表达的肿瘤细胞中，并通过内吞作用释放药物。这种药用机制不仅显著减少了毒副作用，还增强了靶向作用。成绩：2022年全球销售额为达到21.36亿美元，2023年销售额同比增长4%至22.22亿美元。由于T-DM1仅限于HER2+乳腺癌和仿制药的竞争，销售额2026年将为23亿美元。由Verma等人组织的EMILIA项目证实了T-DM1在HER2阳性晚期乳腺癌患者中的临床作用。在使用T-DM1和紫杉醇治疗的her2阳性晚期或转移的乳腺癌患者中，T-DM1显示出增强的治疗疗效、更高的安全性和更少的不良反应（图三）。轻微的不良反应包括疲劳（49.3%）、恶心（49.3%）、血清天冬氨酸转氨酶升高（43.5%）、发热（40.6%）和头痛（40.6%）。图二：早期公布的研究结果揭示T-DM1组的生存率要优于拉帕替尼联合卡培他滨（9.6比6.4个月）34Inotuzumab ozogamicin (InO)公司：Wyeth Pharmaceuticals Inc结构：通过酸介导不稳定剪接，将靶向CD22的人IgG4单抗与细胞毒性化疗药物calicheamicin偶联而成。适应症：急性淋巴母细胞白血病（ALL）作用机理：InO与表达cd22的肿瘤细胞的结合启动了InO-CD22复合物的内吞作用，导致复合物亚基间连接的水解。随后细胞毒性药物的激活诱导双链DNA断裂，导致细胞周期阻滞和细胞死亡。（CD22抗原是一种135-kDaI的跨膜唾液酸糖蛋白，几乎存在于所有B细胞的细胞质中，并在B细胞上特异性表达。CD22抗原主要表达于同时带有IgM 和IgD的B细胞中。）InO是挽救晚期ALL患者的一种有效措施，它使更多的患者有机会接受干细胞移植，实现长期生存。它最常见的不良反应包括中性粒细胞减少（28%）、AST增加（26%）、恶心（21%）、呕吐（17%）、疲劳（15%）和发热性中性粒细胞减少（15%）。5Moxetumomab pasudotox (MP)公司：阿斯利康意义：20多年来第一个批准用于HCL治疗的药物。结构：靶向CD22的莫西美单抗、假单胞菌外毒素a的38 kDa片段和连接物mc-VC-PABC。适应症：复发/难治性毛细胞白血病（HCL）的成年患者，这些患者对至少两种系统性治疗（包括嘌呤核苷类似物）没有反应。图三：MP开发的重要时间节点4MP最常见的副作用 (3-4级）包括淋巴细胞计数下降（20%）、无症状低磷血症（10%）和贫血（10%）。更新的数据证实，MP在经过大量预处理的HCL患者中表现出较高的持久反应率和最小的疾病残留率。因此它被认为是安全的、可控的治疗方案。6Polatuzumab vedotin (PV)公司：Genetech结构：抗体CD79b通过一个可切割的二肽连接（mc-VC-PABC）与MMAE连接组成适应症：复发/难治的弥漫性大B细胞淋巴瘤（DLBCL）的成人患者作用机理：通过泛素/蛋白酶体系统诱导BCL-2蛋白家族成员MCL-1的降解。成绩：2023年Polivy销售额同比增长108%，至9.46亿美元。预计2026年，PV的全球销售额为8.5亿美元当PV与venetoclax和抗cd20抗体obinutuzumab或利rituximab联合使用时，MCL-1拮抗作用导致非霍奇金淋巴瘤（NHL）消退。重要的是，消退即使在停止治疗后仍然持续，相当比例的患者对治疗反应积极。然而，另一项研究显示，PV联合rituximab和lenalidomide治疗复发/难治性DLBCL患者没有达到预定的治疗效果阈值。最常见的3-4级副反应为中性粒细胞减少症和血小板减少症。7Enfortumab vedotin (EV)公司：安斯泰来和辉瑞结构：通过可切割连接将抗Nectin-4的抗体与细胞毒性药物MMAE结合。适应症：局部晚期或转移性尿路上皮癌（la/ mUC）全局治疗作用机理：EV与Nectin-4结合后，形成一个复合物，会在表达Nectin-4的细胞中被内吞。随后释放的MMAE与细胞微管蛋白结合，破坏微管网络，导致细胞周期阻滞和细胞凋亡。成绩：2022年全球销售额已达7.54亿美元，2023年销售额达到10.3亿美元。预计2026年的全球销售额将达35亿美元I期剂量递增研究EV-101涉及112例接受单药EV治疗的mUC患者。结果显示，研究者评估的有效药物反应率为43%，平均药物反应持续7.4个月。存活率中位数为12.3个月，1年存活率为51.8%。最常见的治疗相关不良事件（TRAEs）的发生率为30%，包括疲劳、脱发、食欲下降、味觉障碍、恶心、周围感觉神经病变、瘙痒和腹泻。FDA批准了EV与pembrolizumab联合治疗（EV+P）为突破治疗（breakthrough therapy）方案，并批准其作为不适合顺铂疗法的la/ mUC患者的一线治疗。8Trastuzumab deruxtecan (T-DXd)公司：Daiichi Sankyo Company, Ltd 结构：Trastuzumab （一种靶向HER2的人源化单抗）与依沙替康（exatecan）衍生物（拓扑异构酶I抑制剂）结合适应症：不可切除或转移性her2阳性乳腺癌患者作用机理：与T-DM1相比，T-DXd可以运载更多的细胞毒性药物。它优越的膜通透性使它能够通过“旁观者效应”杀死更多的肿瘤细胞。成绩：由于T-DXd可用于多种乳腺癌亚群（HER2+、HR+/HER2-和三重阴性）且治疗时间长，预计2026年将以62亿美元成为销量最高的ADC。在一项开放标签、剂量递增和剂量扩大的I期试验中，研究人员评估了T-DXd在表达HER2的晚期实体肿瘤中的安全性、耐受性和药物活性。结果显示，111例患者中有66例证产生了药理反应，111例患者中有104例病情得到控制。所有患者都经历过至少一次不良反应。常见的3级或以上严重的不良反应包括贫血（17%）、中性粒细胞减少（14%）、白细胞减少（9%）和血小板减少（8%）。此外，19%的患者经历了至少一次严重的不良反应，20例患者发生了间质性肺病、组织性肺炎或肺炎。表一：T-DXd各次临床试验的关键数据59Sacituzumab govitecan (SG)公司：Immunomedics意义：全球唯一获批的靶向 Trop-2 ADC 药物结构：包括一个抗trop-2抗体、一个SN-38药物载荷（伊立替康irinotecan的一种活性代谢物）和一个CL2A化学连接适应症：转移性三阴性乳腺癌（TNBC）成人患者作用机理：滋养层细胞表面抗原2（Trop-2）是一种40-kDa的糖蛋白，也被称为肿瘤相关钙信号转换器-2。它在各种实体肿瘤的发展和转移中起着至关重要的作用。SG引人注目的特点包括它对Trop-2的靶向性，以及它运载的中毒性药物SN-38。SG拥有高药物抗体比（7-8：1）。这些都会降低它的脱靶毒性。成绩：上市的首个完整年度业绩为3.8亿美元，2022年全球销售额为6.81亿美元，2023年Trodelvy销售额首次突破十亿美元大关，同比增长56%至 10.63 亿美元。2026销售额预计为11亿美元（表二）表二：SG家族产品销售额临床试验NCT03547973证明了SG治疗在基于铂和ICI治疗失败的局部晚期或转移性尿路上皮癌患者中的临床有效性和安全性。此外，一些研究表明，对EV耐药的细胞对SG仍然敏感，这使得SG可能在大多数膀胱癌亚型中有效，包括那些使用EV治疗的膀胱癌，这标志着尿路上皮癌患者治疗的显著发展。10Belantamab mafodotin (Blenrep)公司：GSK意义：Blenrep是全球获批的第一款BCMA靶向疗法结构：一种靶向B细胞成熟抗原（BCMA）的抗体药物偶联物（ADC），IgG1抗体，通过抗蛋白酶降解的连接子，连接微管抑制剂MMAF组成。适应症：作为一种单药疗法，用于治疗先前已接受过至少4种疗法、且其疾病对至少一种蛋白酶体抑制剂/免疫调节剂/CD38单抗难治、在最后一次治疗中被证明疾病进展的复发或难治性多发性骨髓瘤（R/R MM）成人患者。成绩：Blenrep在 2022 年11 月的验证性 III 期试验中失败，导致 FDA 要求葛兰素史克（GSK）当月将该药物从美国市场撤出。同时相较于其他ADC产品，2021年该产品销量1.22亿美元，2022年1.43亿美元。但在2023年11 月 27 日， Blenrep 二线治疗复发或难治性多发性骨髓瘤（R/R MM）III 期临床 DREAMM-7 试验达到无进展生存期（PFS）的中期主要终点，面临多项BCMA产品的市场竞争，Blenrep的市场前景面临挑战。11Loncastuximab tesirine (LT)公司：ADC Therapeutics结构：包括一个人源化的抗人CD19单抗，通过缬氨酸-丙氨酸连接体连接到吡咯苯二氮卓类（pyrrolobenzodiazepine）二聚体毒素上（图五）。适应症：二线或以上全身治疗的复发/难治性LBCL，包括未指明的DLBCL、低级别淋巴瘤引起的DLBCL和高级别b细胞淋巴瘤。最常见的不良反应包括中性粒细胞减少、血小板减少和伽马-谷氨酰基转移酶升高，39%的患者经历了严重的不良事件，包括中性粒细胞减少、胸腔积液、贫血、心包积液和非心源性胸痛。图四：LT的作用机制图612Tisotumab vedotin (TV)公司：Seagen意义：宫颈癌唯一获批ADC结构：与MMAE结合的完全人源单抗（靶向TF）作用机理：组织因子（TF），又称凝血反应蛋白激酶、凝血因子III或CD142，是一种跨膜糖蛋白。其主要功能是启动外源性凝血途径。TF常在癌细胞表面表达，在肿瘤生长、血管生成和转移中发挥重要作用。TV含有的单抗靶向TF，导致MMAE的内吞和细胞毒性作用。适应症：化疗后有肿瘤生长的成年患者的复发或转移性宫颈癌（r/mCC）在一项I/II期开放标签、剂量递增和扩展研究（innovaTV201；NCT02001623）中，在TF表达的转移性实体肿瘤中评估了TV的安全性、耐受性、药代动力学和抗肿瘤活性。最常见的不良反应是脱发、鼻出血、恶心、结膜炎、疲劳和干眼症。13Mirvetuximab soravtansin (MIRV)公司：ImmunoGen结构：使用FRα靶向抗体，通过一种可裂解的连接物与微管抑制剂相连适应症：治疗FRα表达阳性、铂耐药上皮性卵巢、输卵管或原发性腹膜癌的成年患者，这些患者之前接受过1-3种全身治疗方案作用机理：叶酸受体α（FRα）对叶酸具有较高的亲和力，促进其通过内吞作用运输到细胞质。虽然FRα在正常组织中通常以低水平表达，但它在各种上皮性肿瘤中经常异常表达，包括上皮性卵巢癌、子宫内膜腺癌、TNBC和NSCLC。MIRV含有的单抗靶向FRα。目前，正在进行的研究主要集中在MIRV与其他药物联合治疗卵巢癌患者的安全性和有效性。包括MIRV联合卡铂治疗复发、铂敏感的上皮性卵巢或输卵管癌患者的安全性和抗肿瘤活性。MIRV最常见的不良反应包括腹泻、视力模糊、恶心和疲劳、参考文献：1. Liu K, Li M, Li Y, Li Y, Chen Z, Tang Y, Yang M, Deng G, Liu H. A review of the clinical efficacy of FDA-approved antibody‒drug conjugates in human cancers. Mol Cancer. 2024 Mar 23;23(1):62. doi: 10.1186/s12943-024-01963-7. PMID: 38519953;2. Fenwarth, L.; Fournier, E.; Cheok, M.; Boyer, T.; Gonzales, F.; Castaigne, S.; Boissel, N.; Lambert, J.; Dombret, H.; Preudhomme, C.; et al. Biomarkers of Gemtuzumab Ozogamicin Response for Acute Myeloid Leukemia Treatment. Int. J. Mol. Sci. 2020, 21, 5626.3. Harbeck N, Gluz O, Christgen M, et al. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)–positive early breast cancer (BC): final analysis of the west german study group adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor–positive phase II randomized trial—efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Jul 6. doi: 10.1200/JCO.2016.71.98154. Dhillon S. Moxetumomab Pasudotox: First Global Approval. Drugs. 2018 Nov;78(16):1763-1767. doi: 10.1007/s40265-018-1000-9. Erratum in: Drugs. 2019 Jan;79(1):105. PMID: 30357593;5. Indini A,Rijavec E, Grossi F. Trastuzumab Deruxtecan: Changing the Destiny of HER2Expressing Solid Tumors. Int J Mol Sci. 2021 Apr 30;22(9):4774. doi:10.3390/ijms22094774. PMID: 33946310; PMCID: PMC8125530.6. TsuchikamaK, An Z. Antibody-drug conjugates: recent advances in conjugation and linker chemistries.Protein Cell. 2018 Jan;9(1):33-46. doi: 10.1007/s13238-016-0323-0. Epub 2016Oct 14. PMID: 27743348; PMCID: PMC5777969.封面图来源：pixabay版权声明/免责声明本文为授权转载文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn拜耳Co.Lab上海正式启动招募入驻企业谁说CAR-T不赚钱？为什么医生不愿意开仿制药？点击阅读原文，了解更多！

抗体药物偶联物上市批准申请上市临床结果

2024-04-22

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Kura Oncology Receives Breakthrough Therapy Designation for Ziftomenib in NPM1-Mutant AML

– Ziftomenib is the first investigational treatment to be granted Breakthrough Therapy Designation for NPM1-mutant AML – – Registration-directed trial of ziftomenib in NPM1-mutant AML on track to complete enrollment by mid-2024 – SAN DIEGO, April 22, 2024 (GLOBE NEWSWIRE) -- Kura Oncology Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today announced that its investigational drug, ziftomenib, has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of patients with relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (AML). FDA granted BTD for ziftomenib based on data from Kura’s ongoing KOMET-001 clinical trial in patients with R/R NPM1-mutant AML. BTD is for a drug that treats a serious or life-threatening condition and for which preliminary clinical evidence indicates the drug may demonstrate substantial improvement on a clinically significant endpoint(s) over available therapies. The designation is intended to expedite development and review of drugs, including an organizational commitment by FDA senior managers and experienced review staff as well as eligibility for rolling review and priority review.1 “We are highly encouraged by FDA’s decision to grant Breakthrough Therapy Designation to ziftomenib, recognizing its potential as an innovative medicine for patients with relapsed/refractory NPM1-mutant AML,” said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. “NPM1-mutant AML represents approximately 30% of new AML cases annually, and this designation reflects that NPM1-mutant AML is a disease of significant unmet need for which there is no approved targeted therapy as well as the fact that ziftomenib offers potential to demonstrate substantial improvement over available therapies. We remain committed to bringing ziftomenib to the market as quickly as possible and look forward to working more closely with FDA to bring our ziftomenib program to patients in urgent need of effective treatments.” Kura is on track to complete the registration-directed trial of ziftomenib in R/R NPM1-mutant AML by mid-2024. Ziftomenib is also being evaluated in combination with current standards of care, including venetoclax/azacitidine or cytarabine plus daunorubicin (7+3) in NPM1-mutant and KMT2A-rearranged AML (KOMET-007) and with gilteritinib, FLAG-IDA or LDAC in NPM1-mutant and KMT2A-rearranged AML (KOMET-008). About NPM1-mutant AML AML is the most common acute leukemia in adults and begins when the bone marrow makes abnormal myeloblasts (white blood cells), red blood cells or platelets. Despite the many available treatments for AML, prognosis for patients remains poor and a high unmet need remains. The menin pathway is considered a driver for multiple genetic alterations of the disease, of which NPM1 mutations are among the most common, representing approximately 30% of AML cases. While patients with NPM1-m AML have high response rates to frontline therapy, relapse rates are high and survival outcomes are poor, with only 30% overall survival at 12 months in the R/R setting. Additionally, NPM1 mutations frequently occur with co-mutations in other disease-associated genes, including FLT3, DNMT3A and IDH1/2, with prognosis heavily influenced by the occurrence of co-occurring mutations. Adult patients with NPM1-m AML and select co-mutations and/or R/R disease have a poor prognosis, with median overall survival of only approximately 7.8 months in 2nd line, 5.3 months in 3rd line and 3.5 months following the 4th line2. There are currently no FDA-approved therapies targeting NPM1-m AML. About Ziftomenib Ziftomenib is a novel, once-daily, oral investigational drug candidate targeting the menin-KMT2A/MLL protein-protein interaction for treatment of genetically defined AML patients with high unmet need. In the KOMET-001 Phase 1 study, ziftomenib demonstrated an encouraging safety pro tolerability with reported events most often consistent with features and manifestations of underlying disease. Clinical activity of ziftomenib as a monotherapy was optimal at the 600 mg daily dose and a 35% complete remission rate was observed in 20 patients with NPM1-mutant AML treated at the recommended Phase 2 dose (600 mg). Ziftomenib has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of AML. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib. About Kura Oncology Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways. Ziftomenib is a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction for the treatment of genetically defined AML patients with high unmet need. Kura is currently enrolling patients in a Phase 2 registration-directed trial of ziftomenib in NPM1-mutant R/R AML (KOMET-001). The Company is also conducting a series of studies to evaluate ziftomenib in combination with current standards of care, including venetoclax/azacitidine and 7+3 in NPM1-mutant and KMT2A-rearranged newly diagnosed and R/R AML (KOMET-007) and with gilteritinib, FLAG-IDA or LDAC in NPM1-mutant and KMT2A-rearranged R/R AML (KOMET-008). Tipifarnib, a potent and selective farnesyl transferase inhibitor (FTI), is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent head and neck squamous cell carcinoma (KURRENT-HN). Kura is also evaluating KO-2806, a next-generation FTI, in a Phase 1 dose-escalation trial as a monotherapy and in combination with cabozantinib in clear cell renal cell carcinoma and with adagrasib in KRASG12C-mutated non-small cell lung cancer (FIT-001). For additional information, please visit Kura’s website at and follow us on X and LinkedIn. Forward-Looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of ziftomenib, potential benefits of combining ziftomenib with appropriate standards of care, and progress and expected timing of the ziftomenib program and clinical trials. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Kura may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings, applications and other interactions with regulatory bodies, risks associated with reliance on third parties to successfully conduct clinical trials, the risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to the Company's periodic and other filings with the Securities and Exchange Commission, which are available at . Such forward-looking statements are current only as of the date they are made, and Kura assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Contacts Investors: Pete De Spain Executive Vice President, Investor Relations & Corporate Communications (858) 500-8833 pete@kuraoncology.com Media: Alexandra Weingarten Associate Director, Corporate Communications & Investor Relations (858) 500-8822 alexandra@kuraoncology.com 1 U.S. Food and Drug Administration. Breakthrough Therapy Designation. Accessed April 23, 2024. 2 Issa G, et al. Blood Adv 2023;7(6):933-42.

临床1期孤儿药临床2期突破性疗法临床结果

100 项与磷酸氟达拉滨相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01907	磷酸氟达拉滨	L01BB05	-

研发状态

适应症	最高研发状态	国家/地区	公司
慢性淋巴细胞白血病	批准上市	加拿大更多	Sanofi 更多
淋巴瘤	批准上市	日本更多	Sanofi KK 更多
小淋巴细胞淋巴瘤	临床2期	美国更多	The University of Texas MD Anderson Cancer Center 更多
难治性慢性淋巴细胞白血病	终止	-	-
大颗粒淋巴细胞白血病	无进展	-	National Cancer Institute 更多

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临床结果

适应症

分期

评价

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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


NCT01033552 (CTgov)	临床1/2期	大疱性表皮松解	32	Mesenchymal stem cell transplantation+Myeloablative Busulfan+Fludarabine+Cyclophosphamide (RDEB Mac)	衊構遞製夢構觸獵窪鹽(遞鏇窪鬱夢鏇網積選襯) = 簾網餘積齋餘築壓膚壓網夢製淵繭膚襯衊觸網 (製積壓鬱願膚繭窪鹽獵, 遞鹽積夢壓遞觸網鑰膚 ~ 鑰憲願壓構廠淵鹹齋簾) 更多	-	2024-04-03
				Anti-Thymocyte Globulin+Fludarabine+Cyclophosphamide (RDEB RIC)	衊構遞製夢構觸獵窪鹽(遞鏇窪鬱夢鏇網積選襯) = 選憲簾壓壓鬱壓鑰壓鹽網夢製淵繭膚襯衊觸網 (製積壓鬱願膚繭窪鹽獵, 鏇鑰積選淵壓窪蓋繭遞 ~ 範繭獵餘願壓鹹遞鬱餘) 更多
NCT03333486 (CTgov)	临床2期	镰状细胞血症 \| 地中海贫血 \| Shwachman-Diamond综合征 ... 更多	31	Peripheral Blood Stem Cell Transplantation+Fludarabine Phosphate+CYCLOPHOSPHAMIDE	襯鑰觸範遞鑰選糧壓窪(製鬱膚醖夢齋繭膚簾鹹) = 積糧壓製遞繭餘衊鬱糧襯蓋蓋餘壓選醖衊觸淵 (選網鑰簾鏇衊範構積繭, 鬱夢艱製鏇夢鑰築觸蓋 ~ 鹽構醖積淵鏇簾醖膚衊) 更多	-	2024-04-02
NCT03056339 (CTgov)	临床1/2期	CD19 表达恶性肿瘤 \| 慢性淋巴细胞白血病 \| 急性淋巴细胞白血病	49	steroids+Mesna+Fludarabine+cyclophosphamide+AP1903 (Group 1: 1x105 NK Cells /kg)	餘鑰壓壓憲鹹構鹹顧繭(窪構築壓衊願壓範淵範) = 淵製鹽膚獵糧鑰選衊觸鹽獵願簾積顧淵廠鏇範 (餘膚顧糧壓網簾醖鏇齋, 鑰範鏇鹹壓醖淵網簾鑰 ~ 獵艱獵壓遞繭蓋夢選築) 更多	-	2024-03-25
				steroids+Mesna+Fludarabine+cyclophosphamide+AP1903 (Group 2: 1x106 NK Cells /kg)	餘鑰壓壓憲鹹構鹹顧繭(窪構築壓衊願壓範淵範) = 壓觸願網獵鹹膚鏇餘繭鹽獵願簾積顧淵廠鏇範 (餘膚顧糧壓網簾醖鏇齋, 範窪窪糧選膚鏇網憲衊 ~ 繭鬱餘鬱壓蓋蓋齋簾窪) 更多
NCT01858740 (CTgov)	临床2期	移植物抗宿主病 \| 加速期慢性骨髄性白血病 \| 费城染色体阳性慢性粒细胞白血病 ... 更多	20	Peripheral Blood Stem Cell Transplantation+Fludarabine Phosphate+Tacrolimus+Methotrexate+Thiotepa	製襯獵顧鹽窪齋遞齋夢(遞築蓋顧艱憲遞願選廠) = 顧衊窪蓋積築壓糧衊鹹夢餘淵遞網蓋遞簾遞遞 (製膚醖範醖製願壓壓積, 襯蓋繭鬱構鹽築廠壓範 ~ 夢選壓廠糧簾遞範艱壓) 更多	-	2024-03-12
NCT02251821 (CTgov)	临床2期	原发性骨髓纤维化	61	Umbilical Cord Blood Transplantation+Fludarabine Phosphate+Busulfan+CYCLOPHOSPHAMIDE+Melphalan+Tacrolimus+Ruxolitinib+mycophenolate mofetil+Methotrexate	糧構衊蓋鹹窪膚衊艱選(簾衊衊鏇廠廠夢構願艱) = 積觸鏇鏇製憲鬱衊醖壓鏇鹽襯網鹹夢鏇齋淵鹽 (觸鏇齋膚製衊築鹹廠鏇, 遞蓋網製窪襯範蓋獵齋 ~ 夢鏇淵膚艱廠鹹蓋醖鑰) 更多	-	2024-03-05
NCT02441803 (CTgov)	临床2期	急性髓性白血病	11	Stem Cell Infusion+Clofarabine+Fludarabine+Busulfan+Decitabine+cytarabine+Idarubicin (Matched Sibling Donor Group)	築鏇襯鏇膚願遞襯範範(鏇繭鹹製製簾衊築遞襯) = 構衊鹹壓鹹鑰糧糧願鬱衊築壓製鏇餘網夢網範 (艱製鏇選醖簾構窪築齋, 廠願糧廠築選壓範鏇窪 ~ 艱糧積製鏇襯廠觸淵選) 更多	-	2024-01-17
				Stem Cell Infusion+Clofarabine+Fludarabine+Busulfan+Cyclophosphamide+Decitabine+Tacrolimus+mycophenolate mofetil+cytarabine+Idarubicin (Haploidentical Donor Group)	築鏇襯鏇膚願遞襯範範(鏇繭鹹製製簾衊築遞襯) = 衊鑰鹽獵範構鹹範蓋夢衊築壓製鏇餘網夢網範 (艱製鏇選醖簾構窪築齋, 構蓋齋網積鹹廠壓簾顧 ~ 製齋積窪窪淵構淵願餘) 更多
ISRCTN78449203 (Pubmed)	临床3期	急性髓性白血病 NPM1 \| FLT3	-	Fludarabine, Cytarabine, Granulocyte Colony-Stimulating Factor, and Idarubicin with Gemtuzumab Ozogamicin	壓窪範窪鹽壓艱觸簾淵(築廠獵齋繭艱膚願製憲) = 構繭製廠鏇衊遞鹹製艱醖獵簾壓願淵糧夢獵衊 (範顧夢壓夢鏇淵鑰鹽構 ) 更多	-	2024-01-12
				Daunorubicin and Ara-C with Gemtuzumab Ozogamicin	壓窪範窪鹽壓艱觸簾淵(築廠獵齋繭艱膚願製憲) = 衊構餘廠鑰鑰壓糧糧鹽醖獵簾壓願淵糧夢獵衊 (範顧夢壓夢鏇淵鑰鹽構 ) 更多
NCT01850108 (CTgov)	N/A	镰状细胞血症	26	Bone marrow transplantation+Mesna+Fludarabine+Thymoglobulin+Sirolimus+Mycophenolate mofetil (MMF)+Cyclophosphamide (CTX)	製鏇選膚襯艱遞憲選築(壓鬱憲遞獵鑰艱繭艱廠) = 窪鬱衊齋廠簾蓋鹹襯鹹齋繭糧醖構膚觸繭構願 (衊蓋積夢膚構積觸願製, 鑰憲醖廠糧蓋蓋糧網鏇 ~ 獵積蓋選製醖範蓋艱蓋) 更多	-	2024-01-10
ASH2023	N/A	急性髓性白血病	439	Fludarabine/Melphalan	積淵觸壓鹽鏇壓獵積窪(餘鹽鬱膚壓鏇網壓鏇齋) = 壓觸夢蓋網鏇夢夢廠鏇築構鏇衊艱憲鏇蓋觸鑰 (窪醖顧築繭構鑰顧鏇膚, ±3.9)	-	2023-12-11
				Fludarabine/BusulfanFludarabine/Busulfan	積淵觸壓鹽鏇壓獵積窪(餘鹽鬱膚壓鏇網壓鏇齋) = 糧鬱遞鑰衊觸積鏇夢淵築構鏇衊艱憲鏇蓋觸鑰 (窪醖顧築繭構鑰顧鏇膚, ±3.9)
ASH2023	N/A	-	59	Bendamustine	繭衊淵憲簾鹹淵鬱遞簾(範艱製夢壓獵艱膚選夢) = 醖製襯製齋憲淵鬱廠襯範憲廠衊築網鹽窪蓋廠 (餘顧簾鬱選衊簾範艱膚 ) 更多	-	2023-12-11
				Fludarabine-Cyclophosphamide	廠簾獵廠鏇餘獵餘選鏇(網網鏇製艱鹽蓋簾齋醖) = 製夢遞醖廠廠齋廠構齋鹽夢夢糧願餘選齋遞淵 (餘憲製願獵襯襯蓋選夢 ) 更多