A Randomised, Open-label, Phase II, Dose/Schedule Optimisation Study of NUC-3373/Leucovorin/Irinotecan Plus Bevacizumab (NUFIRI-bev) Versus 5-FU/Leucovorin/Irinotecan Plus Bevacizumab (FOLFIRI-bev) for the Treatment of Patients With Previously Treated Unresectable Metastatic Colorectal Cancer

This is a randomized, open-label, dose/schedule optimization study comparing NUC-3373/leucovorin (LV)/irinotecan plus bevacizumab (NUFIRI-bev) to 5-FU/LV/irinotecan plus bevacizumab (FOLFIRI-bev) for the treatment of patients with unresectable metastatic colorectal cancer.
A total of 171 patients will be randomized 1:1:1 to either NUFIRI-bev on a weekly NUC-3373 schedule, NUFIRI-bev based on an alternate weekly NUC-3373 schedule, or FOLFIRI bev on an alternate weekly schedule. The main objectives are to assess and compare the efficacy and safety of the 3 regimens. Pharmacokinetics will be assessed on the 2 NUFIRI arms.

开始日期2023-04-18

申办/合作机构

NuCana Plc

NCT05714553 / Recruiting临床1/2期

A Phase Ib/II Open Label, Multi-arm, Parallel Cohort Dose Finding and Expansion Study to Assess the Safety, Pharmacokinetics and Efficacy of NUC-3373, a Nucleotide Analogue, Given in Combination With Standard Approved Agents in Patients With Advanced Solid Tumours

This study is an open-label, multi-arm, parallel cohort, dose validation and expansion design. The study is modular in design, allowing evaluation of the safety, efficacy and pharmacokinetics (PK) of NUC-3373 in combination with other agents for the treatment of patients with different tumour types.
Each module is designed to evaluate a different NUC-3373 combination and consists of a dose-validation phase (Phase Ib) and a dose-expansion phase (Phase II).
Phase Ib of each module will determine the safety and tolerability of the combinations for further clinical evaluation in Phase II. Approximately 6-20 evaluable patients will be enrolled in the Phase Ib stage of each module to determine safety, tolerability, and preliminary efficacy of NUC-3373 in combination with other agents. Each module will then move into Phase II to enable a further assessment of safety and efficacy in approximately 20-40 patients.
Module 1 will assess NUC-3373 + leucovorin (LV) in combination with pembrolizumab for the treatment of patients with advanced/metastatic solid tumours who have progressed on ≤2 prior therapies for metastatic disease, that may have included 1 prior immunotherapy-containing regimen (either monotherapy or in combination with chemotherapy) or who have not progressed but where addition of NUC-3373 + LV to standard pembrolizumab monotherapy may be appropriate (e.g., patients who could not tolerate post- immuno-oncology (IO) standard of care therapy).
Module 2 will assess NUC-3373 + LV in combination with docetaxel for the treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC) or pleural mesothelioma who have progressed on, or were unable to tolerate, 1 or 2 prior lines of cytotoxic chemotherapy-containing regimens for advanced/metastatic disease.
The opening of each module will be at the discretion of the Sponsor. Further modules may be added as non-clinical and clinical data become available to support additional NUC-3373 combinations and tumour types.

开始日期2023-03-08

申办/合作机构

NuCana Plc

NCT03428958 / Completed临床1/2期

A Phase Ib/II Open Label Study to Assess the Safety and Pharmacokinetics of NUC-3373, a Nucleotide Analogue, Given in Combination With Standard Agents Used in Colorectal Cancer Treatment

This is a three-part study of NUC-3373 administered by intravenous (IV) infusion across two administration schedules, either as monotherapy or as part of various combinations with agents commonly used to treat CRC (leucovorin, oxaliplatin, irinotecan, bevacizumab, cetuximab and panitumumab). The primary objective is to identify a recommended dose and schedule for NUC-3373 when combined with these agents.

开始日期2018-10-16

申办/合作机构

NuCana Plc

100 项与 Fosifloxuridine nafalbenamide 相关的临床结果

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100 项与 Fosifloxuridine nafalbenamide 相关的转化医学

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100 项与 Fosifloxuridine nafalbenamide 相关的专利（医药）

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项与 Fosifloxuridine nafalbenamide 相关的文献（医药）

2023-05-01·Cancer chemotherapy and pharmacology

The novel anti-cancer fluoropyrimidine NUC-3373 is a potent inhibitor of thymidylate synthase and an effective DNA-damaging agent.

Article

作者: Tang, Peijun ; Mullen, Peter ; Dickson, Alison L ; Harrison, David J ; Zickuhr, Greice M ; McKissock, Fiona G ; Czekster, Clarissa M ; Bré, Jennifer ; Zhang, Ying ; Read, Oliver J

INTRODUCTIONFluoropyrimidines, principally 5-fluorouracil (5-FU), remain a key component of chemotherapy regimens for multiple cancer types, in particular colorectal and other gastrointestinal malignancies. To overcome key limitations and pharmacologic challenges that hinder the clinical utility of 5-FU, NUC-3373, a phosphoramidate transformation of 5-fluorodeoxyuridine, was designed to improve the efficacy and safety profile as well as the administration challenges associated with 5-FU.METHODSHuman colorectal cancer cell lines HCT116 and SW480 were treated with sub-IC₅₀ doses of NUC-3373 or 5-FU. Intracellular activation was measured by LC-MS. Western blot was performed to determine binding of the active anti-cancer metabolite FdUMP to thymidylate synthase (TS) and DNA damage.RESULTSWe demonstrated that NUC-3373 generates more FdUMP than 5-FU, resulting in a more potent inhibition of TS, DNA misincorporation and subsequent cell cycle arrest and DNA damage in vitro. Unlike 5-FU, the thymineless death induced by NUC-3373 was rescued by the concurrent addition of exogenous thymidine. 5-FU cytotoxicity, however, was only reversed by supplementation with uridine, a treatment used to reduce 5-FU-induced toxicities in the clinic. This is in line with our findings that 5-FU generates FUTP which is incorporated into RNA, a mechanism known to underlie the myelosuppression and gastrointestinal inflammation associated with 5-FU.CONCLUSIONTaken together, these results highlight key differences between NUC-3373 and 5-FU that are driven by the anti-cancer metabolites generated. NUC-3373 is a potent inhibitor of TS that also causes DNA-directed damage. These data support the preliminary clinical evidence that suggest NUC-3373 has a favorable safety profile in patients.

2023-01-02·SAR and QSAR in Environmental Research

Energy decomposition and waterswapping analysis to investigate the SNP associated DPD mediated 5-FU resistance

Article

作者: Silakari, O. ; Verma, H. ; Singh, P.K. ; Raju, B. ; Doshi, J. ; Narendra, G.

5-fluorouracil is an essential component of systemic chemotherapy for colon, breast, head, and neck cancer patients. However, tumoral overexpression of the dihydropyrimidine dehydrogenase has rendered 5-FU clinically ineffective by inactivating it to 5'-6'-dihydro fluorouracil. The responses to 5-FU in terms of efficacy and toxicity greatly differ depending upon the population group, because of variability in the DPD activity levels. In the current study, key active site amino acids involved in the 5-FU inactivation were investigated by modelling the 3D structure of human DPD in a complex with 5-FU. The identified amino acids were analyzed for their possible missense mutations available in dbSNP database. Out of 12 missense SNPs, four were validated either by sequencing in the 1000 Genomes project or frequency/genotype data. The recorded validated missense SNPs were further considered to analyze the effect of their respective alterations on 5-FU binding. Overall findings suggested that population bearing the Glu611Val DPD mutation (rs762523739) is highly vulnerable to 5-FU resistance. From the docking, electrostatic complementarity, dynamics, and energy decomposition analyses it was found that the above mutation showed superior scores than the wild DPD -5FU complex. Therefore, prescribing prodrug NUC-3373 or DPD inhibitors (Gimeracil/3-Cyano-2,6-Dihydroxypyridines) as adjuvant therapy may overcome the 5-FU resistance.

2021-06-24·Journal of Medicinal Chemistry1区 · 医学

Single Diastereomers of the Clinical Anticancer ProTide Agents NUC-1031 and NUC-3373 Preferentially Target Cancer Stem CellsIn Vitro

1区 · 医学

Article

作者: Slusarczyk, Magdalena ; Pepper, Chris ; McGuigan, Christopher ; Ghazaly, Essam ; Kariuki, Benson M. ; Serpi, Michaela

A 3'-protected route toward the synthesis of the diastereomers of clinically active ProTides, NUC-1031 and NUC-3373, is described. The in vitro cytotoxic activities of the individual diastereomers were found to be similar to their diastereomeric mixtures. In the KG1a cell line, NUC-1031 and NUC-3373 have preferential cytotoxic effects on leukemic stem cells (LSCs). These effects were not diastereomer-specific and were not observed with the parental nucleoside analogues gemcitabine and FUDR, respectively. In addition, NUC-1031 preferentially targeted LSCs in primary AML samples and cancer stem cells in the prostate cancer cell line, LNCaP. Although the mechanism for this remains incompletely resolved, NUC-1031-treated cells showed increased levels of triphosphate in both LSC and bulk tumor fractions. As ProTides are not dependent on nucleoside transporters, it seems possible that the LSC targeting observed with ProTides may be caused, at least in part, by preferential accumulation of metabolized nucleos(t)ide analogues.

项与 Fosifloxuridine nafalbenamide 相关的新闻（医药）

2024-11-17

·药明康德

12个月患者总生存率超90%的抗癌联合疗法；治疗慢性HBV感染的表观遗传沉默剂进入临床…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. Cue Biopharma公司公布了其两款新型生物制品的积极临床数据，其中接受CUE-101联用PD-1抑制剂pembrolizumab一线治疗的HPV阳性复发性/转移性头颈部鳞状细胞癌（R/M HNSCC）患者12个月时的总生存率为91.3%。 2. 胸苷酸合成酶抑制剂NUC-3373联用pembrolizumab在一项临床研究中使1名尿路上皮膀胱癌患者的靶病灶缩小了100%。 3. 用于治疗慢性乙肝病毒（HBV）感染的表观遗传沉默剂TUNE-401在新西兰获批进入1b期临床试验。药明康德内容团队整理 CUE-101、CUE-102：公布1期临床试验的新数据 Cue Biopharma公司公布其CUE-101治疗头颈癌和CUE-102治疗WT1阳性癌症的1期临床试验的积极新数据。CUE-101是该公司开发的一款基于白细胞介素-2（IL-2）的T细胞诱导剂，旨在选择性调节和激活HPV阳性T细胞，以提高疗效，同时减少传统免疫疗法的副作用。CUE-102是一种由两个呈递WT1肽的人白细胞抗原（HLA）分子、四个亲和力减弱的IL-2分子和一个效应减弱的人免疫球蛋白G（IgG1）Fc结构域组成的新型生物制品，被开发作为单一疗法治疗WT1阳性复发/转移性癌症患者。截至2024年9月11日的数据，接受CUE-101联用PD-1抑制剂pembrolizumab一线治疗的HPV阳性R/M HNSCC患者的客观缓解率（ORR）为46%，疾病控制率（DCR）为75%，12个月时的总生存率为91.3%，中位总生存期（OS）为21.8个月。在历史研究KEYNOTE-048中，pembrolizumab单药治疗的ORR为19%，12个月时的总生存率为51%，中位OS为12.3个月。在本研究中，1例患者达到完全缓解（CR），10例患者达到部分缓解（PR），以及7例患者获得了超过12周的持久疾病稳定（SD）。接受该一线联合治疗的PD-L1低表达患者的ORR为50%。截至2024年10月29日的数据，接受CUE-102单药治疗的晚期胰腺癌患者的DCR为67%，其中包括肿瘤负荷减少40%的未确认的PR。有证据表明，WT1特异性CD8阳性T细胞受到了选择性刺激和扩增，而非特异性CD8阳性T细胞的总数没有明显增加。 NUC-3373：公布1b/2期联合治疗临床试验数据 NuCana公司公布了其正在进行的1b/2期模块化研究的初步数据，模块1研究评估了NUC-3373联用PD-1抑制剂pembrolizumab治疗晚期实体瘤患者的疗效，模块2研究评估了NUC-3373联用多西他赛治疗肺癌患者的疗效。NUC-3373是一种胸苷酸合成酶抑制剂，由核苷类似物5-氟尿嘧啶衍生而来，可导致DNA损伤。模块1包括12名患有各种实体瘤、已用尽所有其他治疗方案的患者，其中9例患者曾接受过PD-1/PD-L1抑制剂的治疗。接受NUC-3373联用pembrolizumab治疗后，患者实现了显著的肿瘤体积缩小，PFS得到延长。2名患者获得了确认的PR，4例患者达到SD。在疗效可评估人群中，ORR为22%，DCR为67%。其中，1例尿路上皮膀胱癌患者接受联合治疗后靶病灶缩小了100%（非靶病灶依然存在），1例BRAF突变转移性皮肤黑色素瘤患者的靶病灶缩小了81%。此外，NUC-3373联合pembrolizumab的耐受性普遍良好。模块2包括4名非小细胞肺癌（NSCLC）或胸膜间皮瘤患者，这些患者在既往含化疗方案中出现疾病进展或无法耐受。患者在接受NUC-3373联用多西他赛治疗后PFS得到延长，2例患者实现了长期的SD。 TUNE-401：在新西兰获批启动1b期临床试验 Tune Therapeutics公司宣布，该公司已获得新西兰药品和医疗器械安全局（Medsafe）的临床试验申请（CTA）批准，将推进其用于治疗慢性HBV感染的表观遗传沉默剂TUNE-401进入1b期临床试验。 TUNE-401是一款潜在"first-in-class"的表观遗传沉默剂，利用Tune Therapeutics的多功能、模块化TEMPO平台所开发。TUNE-401通过脂质纳米颗粒（LNP）将编码活性、HBV靶向的RNA直接递送至肝细胞。在这些细胞内，所递送的RNA被翻译为表观沉默蛋白，靶向整合入宿主细胞的乙肝病毒DNA（intDNA）和共价闭合环状DNA（cccDNA）。cccDNA是一种独特、游离的环状染色体（episomes），可作为病毒进行复制时的模板，是造成HBV患者多年持续感染的原因之一。临床医生认为，关闭这些cccDNA“病毒工厂”是实现HBV功能性治愈的必要前提。TUNE-401不涉及切割或编辑DNA，其导致产生的活性表观沉默蛋白通过添加甲基基团与DNA结合，以抑制或失活病毒基因，同时保持人类基因的完整性。根据新闻稿，TUNE-401是首个获批进入临床，用以治疗常见传染病的表观遗传疗法。 KVA12123：公布1/2期临床试验数据 Kineta公司公布了其正在进行的1/2期临床试验的最新进展，该试验评估了其新型在研VISTA阻断免疫疗法KVA12123单药或与PD-1抑制剂pembrolizumab联用在晚期实体瘤患者中的治疗效果。KVA12123是一种单克隆抗体疗法，需每周输注两次。通过将独特的表位与优化的IgG1 Fc区相结合，KVA12123单药在临床前模型中显示出强大的肿瘤生长抑制作用，且在临床试验中没有报告细胞因子释放综合征（CRS）。KVA12123已被证明能降低VISTA靶点的风险，并提供了一种新的方法来解决肿瘤微环境中的免疫抑制问题，其作用机制与以T细胞为重点的疗法不同且互补。截至2024年10月18日的数据，接受KVA12123单药治疗并至少进行了一次随访扫描的19例患者中，有13名实现了SD。在许多接受KVA12123单药治疗的患者中观察到持久的临床结果，其中1名此前已接受过六线治疗（包括免疫检查点抑制剂治疗）的NSCLC患者已保持SD状态60周。在接受KVA12123联合pembrolizumab治疗并至少进行了一次随访扫描的9例患者中，1例粘液表皮样癌患者获得了PR，靶病灶缩小了54%，非靶病灶获得了CR；1名免疫检查点抑制剂治疗后进展的肾细胞癌患者达到SD，靶病灶缩小了24%。安全性方面，KVA12123的耐受性良好，单药或与pembrolizumab联用在任何剂量水平上都未出现剂量限制性毒性（DLT）。 IDRX-42：公布1/1b期临床试验的新数据 IDRx公司公布了其用于治疗晚期胃肠道间质瘤（GIST）的在研口服小分子KIT酪氨酸激酶抑制剂IDRX-42的1/1b期临床试验数据。IDRX-42旨在选择性地靶向最常见的KIT突变形式，这些突变要么驱动肿瘤细胞的初始生长、增殖和生存，要么使肿瘤对现有疗法产生耐药性。截至2024年9月30日的数据，87例中位治疗线数为四线、疗效可评估患者的ORR为29%，包括1例CR和24例PR。接受IDRX-42作为二线治疗患者的ORR为53%（8/15），包括1例CR和7例PR，这些患者的中位PFS尚未达到。接受IDRX-42作为三线治疗的患者的中位PFS估计为12.9个月。既往未使用过ripretinib、接受IDRX-42作为≥四线治疗的患者在推荐的1b期剂量下，其中位PFS估计为11.0个月。此外，IDRX-42具有良好的安全性，在推荐的1b期剂量下，8%的患者减少了剂量，没有因治疗伴发不良事件而停药的情况。 APV-527：公布1期临床试验数据 Alligator Bioscience公司和Aptevo Therapeutics公司公布了APV-527用于治疗可能表达肿瘤抗原5T4实体瘤患者的1期临床试验数据。APV-527是一种靶向4-1BB和肿瘤抗原5T4的双特异性抗体，仅在与4-1BB和5T4同时结合时才有活性。此次公布的结果显示，16例疗效可评估的患者中有9例（56%）达到SD，其中，1例结肠癌患者已保持SD超过6个月。最长的SD持续时间发生在一名乳腺癌患者中，该患者进入研究时病情发生进展，目前病情保持稳定，且已参与研究超过11个月。安全性方面，APV-527在所有队列中均表现出积极的安全性和耐受性，尚未观察到严重的肝毒性。肝毒性是其他4-1BB靶向治疗的常见副作用，可导致患者停药。 ELI-002：公布1期临床试验的初步数据 Elicio Therapeutics公司公布了其在研治疗性癌症免疫疗法ELI-002用于治疗接受标准局部治疗后仍有疾病复发风险的KRAS突变驱动实体瘤的1期临床试验的初步结果。ELI-002由AMP修饰的KRAS突变体（mKRAS）肽段，和一种AMP修饰的免疫刺激寡核苷酸佐剂ELI-004组成，经皮下给药靶向淋巴结。它能产生RAS特异性杀伤性T细胞，以攻击术后残留肿瘤细胞，有望延长癌症患者缓解并可预防未来复发。初步数据表明，靶向KRAS突变体的T细胞反应持久且呈剂量依赖性，并诱导了针对患者特异性新抗原的反应。观察到无病生存期（DFS）与T细胞反应强度之间存在相关性。此外，ELI-002的1期安全性及耐受性特征依然良好，未观察到DLT或CRS。 GUBamy：公布1期临床试验数据 Gubra公司公布了长效胰淀素（amylin）类似物GUBamy在单剂量递增（SAD）1期临床试验中获得的积极结果。GUBamy耐受性良好，表现出良好的药代动力学特征，半衰期为11天，支持每周一次的给药方案。此外，单剂量的GUBamy剂量依赖性地降低体重，这一效果在试验期间（6周）内持续存在。在所有高剂量组（3.5-6.0 mg）中，受试者在6周试验期内的平均体重下降约3％，而安慰剂组的体重平均增长约1％。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Tune Therapeutics Moves into Clinical Spotlight with TUNE-401: A First-in-Class Epigenetic Silencer for Hepatitis B. Retrieved November 15, 2024 from https://www.businesswire.com/news/home/20241114651346/en/Tune-Therapeutics-Moves-into-Clinical-Spotlight-with-TUNE-401-A-First-in-Class-Epigenetic-Silencer-for-Hepatitis-B、 [2] Gubra announces positive GUBamy Phase 1 SAD data. Retrieved November 15, 2024, from https://storage.mfn.se/c164ef9a-479f-4e2c-8faf-b3b2c5160fe7/gubra-announces-positive-gubamy-phase-1-sad-data.pdf [3] IDRx Announces Updated Phase 1 Data from Ongoing Phase 1/1b StrateGIST 1 Trial of IDRX-42 in Advanced Gastrointestinal Stromal Tumors (GIST) at CTOS 2024. Retrieved November 15, 2024, from https://www.businesswire.com/news/home/20241113773722/en/IDRx-Announces-Updated-Phase-1-Data-from-Ongoing-Phase-11b-StrateGIST-1-Trial-of-IDRX-42-in-Advanced-Gastrointestinal-Stromal-Tumors-GIST-at-CTOS-2024 [4] Kineta Updates KVA12123 Clinical Results from Ongoing Phase 1/2 VISTA101 Study at Society for Immunotherapy of Cancer (2024). Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/08/2977670/0/en/Kineta-Updates-KVA12123-Clinical-Results-from-Ongoing-Phase-1-2-VISTA101-Study-at-Society-for-Immunotherapy-of-Cancer-2024.html [5] Cue Biopharma Presents Positive Updated Data from its Phase 1 Trials of CUE-101 and CUE-102 in Head and Neck Cancer and WT1 Positive Cancers at the SITC 39th Annual Meeting. Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/08/2977826/0/en/Cue-Biopharma-Presents-Positive-Updated-Data-from-its-Phase-1-Trials-of-CUE-101-and-CUE-102-in-Head-and-Neck-Cancer-and-WT1-Positive-Cancers-at-the-SITC-39th-Annual-Meeting.html [6] Elicio Therapeutics Presents Updated Translational Data from ELI-002 Phase 1 AMPLIFY-7P Study at the Society for Immunotherapy of Cancer (“SITC”) 2024 Annual Meeting. Retrieved November 15, 2024, from https://elicio.com/press_releases/elicio-therapeutics-presents-updated-translational-data-from-eli-002-phase-1-amplify-7p-study-at-the-society-for-immunotherapy-of-cancer-sitc-2024-annual-meeting/ [7] NuCana Announces Encouraging Initial Data from Phase 1b/2 Modular Study of NUC-3373 in Combination with Pembrolizumab or Docetaxel. Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/11/2978192/0/en/NuCana-Announces-Encouraging-Initial-Data-from-Phase-1b-2-Modular-Study-of-NUC-3373-in-Combination-with-Pembrolizumab-or-Docetaxel.html [8] First-in-Class Bispecific Antibody, ALG.APV-527, Meets Important Trial Endpoints in Phase 1 Solid Tumor Trial. Retrieved November 15, 2024, from https://alligatorbioscience.se/en/mfn_news/first-in-class-bispecific-antibody-alg-apv-527-meets-important-trial-endpoints-in-phase-1-solid-tumor-trial/ [9] Immunic Announces Publication of Data From Phase 1/1b Clinical Trial of IMU-856 in the Peer Reviewed Journal, The Lancet Gastroenterology & Hepatology. Retrieved November 15, 2024, from https://www.prnewswire.com/news-releases/immunic-announces-publication-of-data-from-phase-11b-clinical-trial-of-imu-856-in-the-peer-reviewed-journal-the-lancet-gastroenterology--hepatology-302303813.html [10] Synthekine Announces Presentation of New Translational Data from Phase 1a/1b Clinical Trial of α/β Biased IL-2, STK-012, at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting. Retrieved November 15, 2024, from https://www.synthekine.com/news/synthekine-announces-presentation-of-new-translational-data-from-phase-1a-1b-clinical-trial-of-%ce%b1-%ce%b2-biased-il-2-stk-012-at-the-society-for-immunotherapy-of-cancer-sitc-39th-annual-meeting/ [11] Infinitopes to Showcase Breakthroughs on Cancer Vaccine Development at SITC 2024: Insight into a double-blind, Phase I/IIa clinical trial. Retrieved November 15, 2024, from https://www.prnewswire.com/news-releases/infinitopes-to-showcase-breakthroughs-on-cancer-vaccine-development-at-sitc-2024-insight-into-a-double-blind-phase-iiia-clinical-trial-302299015.html [12] Mural Oncology Presents Clinical and Preclinical Data Across its Pipeline at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). Retrieved November 15, 2024, from https://ir.muraloncology.com/news-releases/news-release-details/mural-oncology-presents-clinical-and-preclinical-data-across-its [13] Tectonic Therapeutic Announces Positive Phase 1a Results in AHA 2024 Presentation for TX45, a Long-acting, Fc-Relaxin Fusion Protein. Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/11/2978120/0/en/Tectonic-Therapeutic-Announces-Positive-Phase-1a-Results-in-AHA-2024-Presentation-for-TX45-a-Long-acting-Fc-Relaxin-Fusion-Protein.html [14] CG Oncology Announces Nature Medicine Publication of Phase 1b Study Results Evaluating Cretostimogene Grenadenorepvec in Combination with Nivolumab in Muscle-Invasive Bladder Cancer. Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/11/2978266/0/en/CG-Oncology-Announces-Nature-Medicine-Publication-of-Phase-1b-Study-Results-Evaluating-Cretostimogene-Grenadenorepvec-in-Combination-with-Nivolumab-in-Muscle-Invasive-Bladder-Cance.html [15] Next Generation Gene Therapeutics (NGGT) Announces Positive New Data on NGGT002 for the Treatment of Phenylketonuria (PKU). Retrieved November 15, 2024, from https://www.prnewswire.com/news-releases/next-generation-gene-therapeutics-nggt-announces-positive-new-data-on-nggt002-for-the-treatment-of-phenylketonuria-pku-302300911.html [16] Fate Therapeutics Highlights Cancer-selective, HER2-Targeting Profile of FT825 / ONO-8250 CAR T-cell Product Candidate for Treatment of Advanced Solid Tumors at 2024 SITC Annual Meeting. Retrieved November 15, 2024, from https://ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-highlights-cancer-selective-her2-targeting [17] Neurogene Reports Positive Interim Efficacy Data from First Four Low-Dose Pediatric Participants in NGN-401 Gene Therapy Clinical Trial for Rett Syndrome. Retrieved November 15, 2024, from https://ir.neurogene.com/news-releases/news-release-details/neurogene-reports-positive-interim-efficacy-data-first-four-low [18] IND for ATA-200, a Gene Therapy for the Treatment of Limb-Girdle Muscular Dystrophy Type 2C/R5 (LGMD2C/R5), cleared to proceed by FDA. Retrieved November 15, 2024, from https://www.businesswire.com/news/home/20241112690214/en/IND-for-ATA-200-a-Gene-Therapy-for-the-Treatment-of-Limb-Girdle-Muscular-Dystrophy-Type-2CR5-LGMD2CR5-cleared-to-proceed-by-FDA [19] Nammi Therapeutics, Inc. Announces First Patient Dosed with QXL138AM in a Phase 1 Study Evaluating Advanced Solid Tumors and Multiple Myeloma. Retrieved November 15, 2024, from https://www.prnewswire.com/news-releases/nammi-therapeutics-inc-announces-first-patient-dosed-with-qxl138am-in-a-phase-1-study-evaluating-advanced-solid-tumors-and-multiple-myeloma-302299498.html [20] Palleon Pharmaceuticals Presents Results from the Phase 1/2 GLIMMER-01 Trial of E-602 in Combination with Cemiplimab in Patients with Solid Tumors at the Society for Immunotherapy of Cancer (SITC) Annual Meeting. Retrieved November 15, 2024, from https://www.businesswire.com/news/home/20241108273263/en/Palleon-Pharmaceuticals-Presents-Results-from-the-Phase-12-GLIMMER-01-Trial-of-E-602-in-Combination-with-Cemiplimab-in-Patients-with-Solid-Tumors-at-the-Society-for-Immunotherapy-of-Cancer-SITC-Annual-Meeting/ [21] Cerevance’s CVN293 Demonstrated Positive Phase 1 Results in Healthy Volunteers. Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/11/2978299/0/en/Cerevance-s-CVN293-Demonstrated-Positive-Phase-1-Results-in-Healthy-Volunteers.html [22] Cytokinetics Announces Initiation of Phase 1 Clinical Study of CK-4015089. Retrieved November 15, 2024, from https://ir.cytokinetics.com/news-releases/news-release-details/cytokinetics-announces-initiation-phase-1-clinical-study-ck-2#:~:text=SOUTH%20SAN%20FRANCISCO%2C%20Calif.%2C%20Nov.%2011%2C%202024%20%28GLOBE,study%20of%20CK-4015089%20%28CK-089%29%20in%20healthy%20human%20participants. [23] EnteroBiotix Announces Positive Ph1b Clinical Results of EBX-102 in Liver Cirrhosis. Retrieved November 15, 2024, from https://www.enterobiotix.com/news/enterobiotix-positive-clinical-results-ebx-102-liver-cirrhosis [24] GenVivo to Present Phase 1 Trial Results for GEN2, A Personalizing Gene Vector Therapy, at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting. Retrieved November 15, 2024, from https://genvivoinc.com/2024/11/08/genvivo-to-present-phase-1-trial-results-for-gen2-a-personalizing-gene-vector-therapy-at-the-2024-society-for-immunotherapy-of-cancer-sitc-annual-meeting/ [25] Sparian Biosciences Announces Results from the Phase 1 Clinical Trial of First in Class Novel Arylepoxamide Receptor (AEAr) Agonist Analgesic SBS-1000. Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/12/2979419/0/en/Sparian-Biosciences-Announces-Results-from-the-Phase-1-Clinical-Trial-of-First-in-Class-Novel-Arylepoxamide-Receptor-AEAr-Agonist-Analgesic-SBS-1000.html [26] Spyre Therapeutics Announces Positive Interim Results from Phase 1 Healthy Volunteer Trial for SPY001, Its Novel Half-Life Extended anti-α4β7 Antibody for the Treatment of Inflammatory Bowel Disease, with a Half-Life of >90 Days Supporting the Potential for Both Q3M & Q6M Maintenance Dosing. Retrieved November 15, 2024, from https://www.prnewswire.com/news-releases/spyre-therapeutics-announces-positive-interim-results-from-phase-1-healthy-volunteer-trial-for-spy001-its-novel-half-life-extended-anti-47-antibody-for-the-treatment-of-inflammatory-bowel-disease-with-a-half-life-of-90-days-s-302302014.html [27] Nuvectis Pharma Reports Encouraging NXP800 Interim Data Supporting Ongoing Enrollment in Phase 1b Study in Patients with Platinum-Resistant ARID1a-Mutated Ovarian Cancer. Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/14/2981017/0/en/Nuvectis-Pharma-Reports-Encouraging-NXP800-Interim-Data-Supporting-Ongoing-Enrollment-in-Phase-1b-Study-in-Patients-with-Platinum-Resistant-ARID1a-Mutated-Ovarian-Cancer.html [28] Enlivex Announces the Dosing of the First Patient in a Phase I Clinical Trial Evaluating Allocetra in Patients with Psoriatic Arthritis. Retrieved November 15, 2024, from https://enlivex.com/investors/news-releases/enlivex-announces-the-dosing-of-the-first-patient-in-a-phase-i-clinical-trial-evaluating-allocetra-in-patients-with-psoriatic-arthritis/#:~:text=Nes-Ziona%2C%20Israel%2C%20Nov.%2014%2C%202024%20%E2%80%94%20Enlivex%20Therapeutics,an%20affected%20joint%20in%20patients%20with%20psoriatic%20arthritis. 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：本文来自药明康德内容团队，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

临床2期临床结果免疫疗法临床1期

2024-08-30

·FierceBiotech

Another of NuCana's retooled chemotherapies is unable to increase survival in the clinic

"We believe it will be difficult to regain investor interest in the program in other ongoing studies," William Blair analysts concluded. NuCana has seen another of its reworked chemotherapies struggle to prove itself in the clinic, halving the biotech’s stock in post-market trading.The company had been testing NUC-3373—a new chemical entity derived from the widely used chemotherapy ingredient nucleoside analog 5-fluorouracil—in combination with leucovorin, irinotecan and bevacizumab to treat colorectal cancer in the phase 2 NuTide:323 study.But, in a post-market release Aug. 29, the Scottish company announced that the study’s steering committee had decided the combo regimen was unlikely to demonstrate superior progression-free survival compared to the control arm of fluorouracil, leucovorin, irinotecan and bevacizumab.NuCana had been hoping to develop NUC-3373 as a replacement for fluorouracil as a treatment for second-line colorectal cancer, according to the steering committee’s chair Josep Tabernero, M.D., Ph.D.“The premise of this ambitious goal was based on robust non-clinical and clinical data and the NuTide:323 study team are very disappointed with this outcome,” Tabernero said in the release.As a result, NuCana will discontinue the NuTide:323 study. CEO Hugh Griffith described the committee’s conclusion as an “unexpected outcome.”“These results highlight the challenges associated with developing new medicines for patients with complex and heterogenous cancers such as metastatic colorectal cancer,” Griffith said. “We will leverage insights from these data to identify future potential development options for NUC-3373 in colorectal cancer.” A favorable safety profile was observed in all three arms of the study, with only 12 of the 175 patients—four patients in each arm—discontinuing treatment due to adverse events, the biotech pointed out.NuCana has run into similar issues before. Acelarin, the company’s retooled version of Eli Lilly’s chemotherapy Gemzar, was deemed unlikely to successfully complete either a phase 3 metastatic pancreatic cancer trial in 2019 or a late-stage biliary cancer study in 2022. The candidate has since been removed from the biotech’s pipeline.Acelarin, NUC-3373 and NuCana’s other clinical-stage candidate NUC-7738 all use the same ProTide technology, although they are based on different molecules with distinct modes of action. Data from a phase 2 trial of NUC-7738 in combination with Keytruda in patients with melanoma is due to be unveiled next month.“The results of the NuTide:323 study do not impact the ongoing NuTide:303 study, in which NUC-3373 is being combined with either pembrolizumab in solid tumors or docetaxel in patients with lung cancer,” Griffiths added in the release. “Furthermore, we are excited about the potential of NUC-7738, a novel agent that profoundly impacts gene expression in cancer cells and targets multiple aspects of the tumor microenvironment.” That excitement didn’t appear to be enough to reassure investors, who sent NuCana’s shares plunging 48% in the wake of the news, from $7.73 at market close on Thursday to $4 in post-market trading later that day.“Given this was the first controlled trial with NUC-3373, we believe it will be difficult to regain investor interest in the program in other ongoing studies,” William Blair analysts concluded in a note late yesterday evening.“The failures of the company’s phase 3 study with Acelarin and the randomized phase 2 study of NUC-3373 potentially increase perceived risk for the pipeline, and the data with NUC-3373 and NUC-7738 to date have come from single-arm studies, which have the potential to generate biased results,” the analysts added. “In addition, the long-term safety profile of NUC-3373 and other ProTides in the company’s pipeline needs to be established.”

临床2期临床3期临床结果临床终止临床失败

2024-08-30

·Endpoints

NuCana stops Phase 2 as chemotherapy derivative 'unlikely' to meet primary endpoint

Chemotherapy biotech NuCana’s stock $NCNA tanked nearly 50% in premarket trading Friday following a Thursday announcement that it had stopped a Phase 2 trial due to disappointing data. The company said that the study is being discontinued following a pre-planned initial analysis, which found that the combination of NUC-3373 (NuCana’s candidate derived from a chemotherapy agent) with leucovorin, irinotecan and bevacizumab “was unlikely to” hit the primary endpoint of progression-free survival in patients with second-line colorectal cancer. That’s even considering “prognostic imbalances favoring the control arm,” which consists of 5-fluorouracil, leucovorin, irinotecan and bevacizumab, according to the company. NuCana was aiming to develop NUC-3373 as a replacement for 5-fluorouracil, a widely-used chemotherapy, Josep Tabernero, the chair of the study committee, wrote in a statement. While NUC-3373 is derived from 5-fluorouracil, it’s “a new chemical entity” designed to be safer and easier to administer. According to NuCana, it generates much higher concentrations of active anti-cancer metabolites and has a better safety profile. “The premise of this ambitious goal was based on robust non-clinical and clinical data and the NuTide:323 study team is very disappointed with this outcome,” Tabernero added. NuCana CEO Hugh Griffith said the discontinuation of the study doesn’t impact another ongoing trial in which NUC-3373 is combined with either pembrolizumab (Keytruda) in solid tumors, or docetaxel in patients with lung cancer. Griffith added that the company is “excited about the potential of NUC-7738, a novel agent that profoundly impacts gene expression in cancer cells and targets multiple aspects of the tumor microenvironment.” NUC-7738, one of the company’s two candidates, is in a Phase 2 trial evaluating the candidate as a monotherapy in patients with advanced solid tumors and in combination with pembrolizumab in patients with melanoma.

临床2期临床3期临床失败临床终止

100 项与 Fosifloxuridine nafalbenamide 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14859

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
晚期癌症	临床2期	英国	NuCana Plc	2023-03-08
晚期恶性实体瘤	临床2期	英国	NuCana Plc	2023-03-08
食管癌	临床2期	英国	NuCana Plc	2023-03-08
恶性胸膜间皮瘤	临床2期	英国	NuCana Plc	2023-03-08
错配修复缺陷或微高卫星不稳定性结直肠癌	临床2期	英国	NuCana Plc	2023-03-08
非小细胞肺癌	临床2期	英国	NuCana Plc	2023-03-08
肾细胞癌	临床2期	英国	NuCana Plc	2023-03-08
胃癌	临床2期	英国	NuCana Plc	2023-03-08
尿路上皮癌	临床2期	英国	NuCana Plc	2023-03-08
三阴性乳腺癌	临床2期	英国	NuCana Plc	2023-03-08

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05678257 (NuTide:323, NEWS) 人工标引	临床2期	结直肠癌	-	NUC-3373	(願獵憲積願鹹獵鬱鏇顧) = the combo regimen was unlikely to demonstrate superior progression-free survival compared to the control arm of fluorouracil, leucovorin, irinotecan and bevacizumab. 簾製繭願膚壓獵衊構夢 (齋醖夢壓觸鏇衊淵襯鹽 )	不佳	2024-08-30
NCT05678257 (NuTide:323, NEWS) 人工标引	临床2期	结直肠癌	-	fluorouracil, leucovorin, irinotecan and bevacizumab		不佳	2024-08-30
NCT02723240 (NuTide:301, Pubmed) 人工标引	临床1期	晚期癌症	59	NUC-3373	(製鬱襯鏇襯窪積糧鑰鏇) = 鑰蓋鏇顧襯餘糧鏇憲鑰廠觸憲窪鹽淵膚憲壓構 (鏇衊範鬱遞鹹壓餘繭憲 ) 更多	积极	2024-04-02
NCT03428958 (NuTide:302, Corporate Publications) 人工标引	临床1/2期	结直肠癌二线	46	Oxaliplatin+Levofolinate Calcium+NUC-3373	(選憲範簾範憲齋夢選鏇) = Data presented also indicate that NUFOX and NUFIRI have favorable safety profiles when compared to historical data for the 5-FU-containing regimens FOLFOX and FOLFIRI, with lower rates of toxicities such as neutropenia and gastrointestinal disturbances that limit their clinical utility 艱觸觸積鬱築襯襯構醖 (網築憲膚憲製顧糧繭構 )	积极	2022-09-12
NCT03428958 (NuTide:302, Corporate Publications) 人工标引	临床1/2期	结直肠癌二线	46	Irinotecan Hydrochloride+Levofolinate Calcium+NUC-3373		积极	2022-09-12
NCT03428958 (NuTide:302, ESMO2021) 人工标引	临床1期	晚期结直肠腺癌	38	NUC-3373±leucovorin	(願構願顧遞蓋範獵範淵) = 衊簾遞鹹襯窪窪鬱遞鏇憲鏇遞壓顧衊選範觸餘 (遞選範選壓觸遞鏇顧鑰 )	积极	2021-09-16
NCT03428958 (AACR2021)	临床1/2期	晚期结直肠腺癌	37	NUC-3373	(鏇醖鏇醖廠醖壓淵淵製) = 鹽餘網構獵齋遞選遞襯壓憲衊窪膚夢餘齋襯網 (壓選選積網顧選繭範窪 )	-	2021-07-01
NCT03428958 (NuTide:302, ASCO_GI2021)	临床1/2期	转移性结直肠癌	36	NUC-3373	鹽壓餘衊築觸積膚鏇鹽(鏇艱餘繭範鹹顧願構艱) = 襯鹽憲繭廠廠獵構衊顧餘觸淵餘鹹衊憲觸網醖 (構窪齋願範鑰襯遞願遞 ) 更多	-	2021-01-22