更新于：2024-11-21

Levoleucovorin

左亚叶酸

更新于：2024-11-21

概要

概要

基本信息

药物类型

小分子化药

别名

(6S)-5-Formyl-5,6,7,8-tetrahydrofolic acid、(6S)-5-formyltetrahydrofolic acid、(6S)-Folinic acid

+ [11]

靶点-

作用机制-

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [3]

在研适应症

胃癌药物中毒转移性结直肠癌+ [7]

非在研适应症-

原研机构

Spectrum Pharmaceuticals, Inc.

在研机构

Pfizer Inc.

上海汇伦医药股份有限公司

苏州第壹制药有限公司

+ [1]

非在研机构

Takeda Pharmaceutical Co., Ltd.

Lederle Laboratories

最高研发阶段批准上市

首次获批日期

日本 (2005-12-31),

毒性

最高研发阶段(中国)批准上市

特殊审评孤儿药 (美国)

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结构

分子式C20H23N7O7

InChIKeyVVIAGPKUTFNRDU-STQMWFEESA-N

CAS号68538-85-2

关联

项与左亚叶酸相关的临床试验

NCT06662786 / Not yet recruiting临床3期

A Randomized, Open-label Phase 3 Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer

The purpose of this study is to compare how long the participants are disease-free (progression-free survival) when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, oxaliplatin (mFOLFOX6) or 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus cetuximab and mFOLFOX6 or FOLFIRI in adult participants with Kirsten rat sarcoma viral oncogene homolog (KRAS)/ Neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) wild type (WT) unresectable or metastatic left-sided colorectal cancer.

开始日期2024-10-22

申办/合作机构

Janssen Research & Development LLC

NCT06586515 / Recruiting临床1期

A Phase 1a/1b Trial of LY3962673 in Participants With KRAS G12D-Mutant Solid Tumors

The main purpose of this study is to assess safety & tolerability and antitumor activity of LY3962673 as monotherapy and in combination with other chemotherapy agents in participants with KRAS G12D-mutant advanced solid tumor types. The study is expected to last approximately 5 years.

开始日期2024-09-12

申办/合作机构

Eli Lilly & Co.

NCT06509126 / Recruiting临床3期IIT

Randomized Phase 3 Study of Intermittent or Continuous Panitumumab Plus FOLFIRI for First-line Treatment of Patients With Unresectable Left Sided RAS/B-RAF Wild-type Metastatic Colorectal Cancer (IMPROVE-2 Trial)

The investigators hypothesize that intermittent first-line Panitumumab plus FOLFIRI is effective in first line as the same regimen given continuously, resulting in a Time to Treatment Failure (TTF) not inferior to that obtained with standard continuous regimen of Panitumumab plus FOLFIRI, in the treatment of metastatic left sided RAS/B-RAF wild-type colorectal cancer patients.
Correlative mechanistic studies on tissue and blood samples, liquid biopsies, could identify potential biomarkers of efficacy and help understanding the evolutionary dynamics of tumors in response to therapy thus optimizing the treatment approach with a personalized anti-EGFR treatment strategy.

开始日期2024-06-12

申办/合作机构

National Cancer Institute

100 项与左亚叶酸相关的临床结果

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100 项与左亚叶酸相关的转化医学

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100 项与左亚叶酸相关的专利（医药）

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522

项与左亚叶酸相关的文献（医药）

2024-10-03·Japanese Journal of Clinical Oncology

A real-world survey on expensive drugs used as first-line chemotherapy in patients with HER2-negative unresectable advanced/recurrent gastric cancer in the stomach cancer study group of the Japan clinical oncology group

Article

作者: Boku, Narikazu ; Nishina, Tomohiro ; Sasaki, Keita ; Kurokawa, Yukinori ; Machida, Ryunosuke ; Yoshikawa, Takaki

AbstractBackgroundMolecular-targeted drugs and immune checkpoint inhibitors have been developed for various malignant diseases, thereby improving clinical outcomes. However, these drugs are expensive, and few studies have assessed their actual use and costs in Japan. This study aimed to survey the use and costs of first-line chemotherapy for advanced/recurrent gastric cancer (AGC) in real-world settings.MethodsThe survey included patients with human epidermal growth factor receptor type2 (HER2)-negative AGC who initiated first-line chemotherapy from January 2022 to December 2022 at the participating 92 institutions in the Japan Clinical Oncology Group. Data on the regimens were collected using Google Forms. A regimen that costs >500 000 Japanese yen (JPY) per month was defined as expensive.ResultsData on chemotherapy regimens were collected from 2173 patients at all 92 institutions between March 2023 and May 2023. We analyzed 2113 patients who underwent the chemotherapy with recommended regimens and conditionally recommended regimens according to the Japanese Gastric Cancer Treatment Guidelines sixth edition. The expensive regimens were triplet chemotherapy with fluoropyrimidine (S-1 or capecitabine or 5-fluorouracil/levofolinate), oxaliplatin, and nivolumab. Their monthly costs ranged from 767 648 to 771 046 JPY. Nivolumab-containing regimens cost more than 20 times the price of conventional chemotherapy with fluoropyrimidine and oxaliplatin. These regimens were used in 1416 (67%) of 2113 patients: in 71% of patients aged ≤74 years and in 59% of patients aged ≥75 years.ConclusionThe regimens with >20-fold cost of conventional chemotherapy were used as first-line chemotherapy in two-thirds of patients and more than half even in the elderly population with HER2-negative AGC. This finding is important for future health economic studies on drug cost-efficacy.

2024-09-01·Pancreatology

Early tumor shrinkage as a prognostic predictor in chemotherapy-naïve patients with locally advanced pancreatic cancer treated with modified FOLFIRINOX or gemcitabine plus nab-paclitaxel combination therapy: An exploratory analysis of JCOG1407

Article

作者: Nakachi, Kohei ; Kojima, Yasushi ; Sano, Yusuke ; Ikeda, Masafumi ; Shimizu, Satoshi ; Imaoka, Hiroshi ; Kato, Naoya ; Uemura, Kohei ; Yokoyama, Masayuki ; Ozaka, Masato ; Ueno, Makoto ; Tezuka, Shun ; Shirakawa, Hirofumi ; Furuse, Junji ; Terashima, Takeshi ; Unno, Michiaki ; Kobayashi, Satoshi ; Morizane, Chigusa ; Sano, Keiji

BACKGROUNDEarly tumor shrinkage (ETS) is a prognostic predictor for patients treated with chemotherapy in colorectal cancer, although scarce studies evaluated its potential in locally advanced pancreatic cancer (LAPC). In this exploratory analysis of JCOG1407, a randomized phase II study comparing modified 5-fluorouracil, levofolinate, irinotecan, and oxaliplatin (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP), we evaluated whether ETS can predict prognosis of patients with LAPC.METHODSOf the 126 patients enrolled in JCOG1407, 112 with measurable lesions were included in this study. ETS was defined as a ≥20 % reduction in tumor diameter compared with baseline at the initial imaging assessment 6-10 weeks after initiating chemotherapy. Patients were divided into the ETS (achieved ETS) and non-ETS (failed to achieve ETS) groups based on their ETS status. The impact of ETS on overall survival (OS) was compared using multivariable Cox regression analysis.RESULTSFourteen of 55 (25.5 %) and 24 of 57 (42.1 %) patients in the mFOLFIRINOX and GnP arms, respectively, achieved ETS. In the overall population, mFOLFIRINOX arm, and GnP arm, the median OS in the ETS and non-ETS groups was 27.1 and 20.4, 29.8 and 20.6, and 24.1 and 20.4, months, respectively. The adjusted hazard ratios of OS for the ETS group in the overall population, mFOLFIRINOX arm, and GnP arm were 0.451 (95 % confidence interval [CI]: 0.270-0.754), 0.371 (95 % CI: 0.149-0.926), and 0.508 (95 % CI: 0.255-1.004), respectively.CONCLUSIONSETS may be a prognostic predictor in chemotherapy-naïve patients with LAPC treated with mFOLFIRINOX or GnP.

2024-07-02·Journal of Biomolecular Structure and Dynamics

Levoleucovorin inhibits LOXL2 (lysyl oxidase like-2) to control breast cancer proliferation: a repurposing approach

Article

作者: Deshpande, Hemali

Lysyl oxidase like-2 (LOXL2) belongs to copper dependent amine oxidase from the lysyl oxidase family and is associated with breast cancer metastasis This study used multi-stage computational screening and in vitro validations to repurpose FDA approved drugs targeting LOXL2 to control breast cancer progression.Molecular modeling techniques and high-throughput virtual-screening technique was employed to screen FDA-approved drug library for its avid binding to LOXL2.hLOXL2, MDA-MB231 and MCF 7 cells were used for in vitro.Collectively, this repurposing study identified levoleucovorin to bind the active site of LOXL2 protein to inhibit its activity. Further validation of levoleucovorin against LOXL2 activity is warranted toward repurposing levoleucovorin as a therapeutic agent for treating breast cancer patients. validations.Computational modeling of LOXL2 identified putative druggable region at the active site of LOXL2 protein. High-throughput virtual screening predicted levoleucovorin as a best lead drug candidate to have a favorable binding affinity for LOXL2 at its active site. Molecular dynamic simulation predicts levoleucovorin to bind stably and avidly to LOXL2 with favorable interactions. In vitro validations show levoleucovorin significantly inhibited hLOXL2 with and IC50 value of 68.81 μM. Levoleucovorin controlled cell proliferations in MDM-MB 231 and MCF-7 cells with GI50 values of 55.91 μM and 79.20 μM respectively. Further, a dose dependent inhibition of cancer cell migration was noted along with apoptosis induction in these cells with levoleucovorin treatment.Communicated by Ramaswamy H. Sarma.

项与左亚叶酸相关的新闻（医药）

2024-11-06

·CPHI制药在线

老药新用，机制更新：破坏DNA叠加RNA杀死癌细胞，提升疗效！

关注并星标CPHI制药在线自1950年代以来，5-氟尿嘧啶（5-FLUOROURACIL，缩写：5-FU）作为一种化疗药物，已被广泛应用于治疗多种癌症，尤其是血癌和消化道癌症。然而，长期以来，医学界一直认为它通过破坏DNA的结构来发挥作用。最近，一项研究揭示了5-FU在某些癌症类型中并非仅通过影响DNA，而是通过干扰RNA合成来杀死癌细胞。此发现为未来的药物组合开发提供了全新思路。 (文中抽象配图出自：midjourney) 01 DNA效应：5-FU的传统理论在过去几十年里，科学界普遍认为5-FU的抗癌机制在于其破坏DNA合成过程。这一药物会抑制细胞中核苷酸的合成，导致癌细胞在修复过程中失败，最终导致细胞死亡。根据这一理论，5-FU常常被与其他DNA损伤药物如奥沙利铂或伊立替康联合使用，以增强癌细胞的死亡率。 02 发现新途径：RNA损伤的重要性然而，最近麻省理工学院的科学家们发现，5-FU的真正作用机制在于它对RNA的干扰，尤其是在结肠癌和其他胃肠道癌症中。这项研究表明，5-FU在某些癌症类型中的作用方式并不仅仅是通过DNA损伤，而是通过影响RNA合成，特别是核糖体RNA（rRNA），对癌细胞的蛋白质生成过程造成干扰，从而导致癌细胞死亡。研究人员在实验中发现，5-FU与奥沙利铂或伊立替康的联合使用并没有预期的协同效应。在许多情况下，这种组合的效果甚至不如单独使用5-FU或DNA损伤药物。这一现象引发了研究团队的深思，促使他们进一步探讨5-FU的真正作用机制。 03 分解代谢产物：RNA损伤的关键研究进一步表明，5-FU进入细胞后会被分解为两种不同的代谢产物，其中一种代谢产物会干扰DNA合成，而另一种代谢产物则嵌入RNA核苷酸。在结肠癌细胞中，干扰RNA的代谢产物比破坏DNA的代谢产物更有效地杀死癌细胞，特别是对rRNA的损伤，阻碍了细胞内核糖体的形成。核糖体是细胞合成蛋白质的核心组件，当rRNA受到干扰时，细胞无法正常生成新的蛋白质，这直接影响了癌细胞的生存能力。此外，受损的rRNA还会引发细胞内部的自我毁灭机制，即程序性细胞死亡。这种由RNA损伤引发的细胞凋亡成为了5-FU在治疗胃肠道癌症中的关键作用机制。 04 实验数据的支持：临床试验中的观察为了验证实验室的发现，研究团队与其他机构合作，分析了结肠癌患者在临床治疗中接受5-FU与其他化疗药物组合的疗效数据。结果显示，这些药物的组合在许多患者中并未表现出显著的协同作用，这与实验室研究的数据相符，进一步证明了5-FU对RNA的影响比对DNA的影响更为重要。研究人员目前正在深入研究这种RNA损伤是如何引发癌细胞凋亡的。他们推测，细胞内的溶酶体可能感知到受损的rRNA，并通过某种信号通路激活细胞的死亡程序。理解这一过程将有助于开发新的化疗药物或组合，进一步提高5-FU的治疗效果。 05 新药物组合的探索与新药研发前景基于这一发现，科学家们开始研究能与5-FU协同作用的药物，以进一步提高其在治疗胃肠道癌症中的效果。研究表明，某些药物可以通过增强核糖体的生成来与5-FU形成高度协同的组合，从而增加癌细胞的死亡率。另外，研究还发现，将5-FU与破坏DNA的药物联合使用，往往会降低整体治疗效果。部分原因在于，某些破坏DNA的药物会抑制细胞内核糖体的生成，这反而抵消了5-FU对RNA的影响。研究人员建议，改变药物的给药时间表，例如让药物在不同的时间段间隔使用，可能会大幅提高治疗效果。 06 小结综上所述，5-FU作为一种经典的化疗药物，已在数十年的临床应用中证明了其价值。通过新的研究重新理解其全新的作用机制，尤其是其在RNA合成中的干扰作用，研究人员有望开发出更加精确和有效的癌症治疗方案。这一发现不仅有助于提高5-FU的疗效，还为未来的药物开发提供了全新方向，为无数癌症患者带来了新的希望。参考文献： [1]Chen J K, Merrick K A, Kong Y W, et al. An RNA damage response network mediates the lethality of 5-FU in colorectal cancer[J]. Cell Reports Medicine, 2024. [2]Mao H, Zhou J, Yan L, et al. Hybrid films loaded with 5-fluorouracil and Reglan for synergistic treatment of colon cancer via asynchronous dual-drug delivery[J]. Frontiers in Bioengineering and Biotechnology, 2024, 12: 1398730. [3]Tabernero J, Yoshino T, Stintzing S, et al. A Randomized Phase III Study of Arfolitixorin versus Leucovorin with 5-Fluorouracil, Oxaliplatin, and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer: The AGENT Trial[J]. Cancer Research Communications, 2024, 4(1): 28-37. END 【智药研习社线上研习会报名】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

寡核苷酸核酸药物信使RNA

2024-11-01

·恒瑞医药

全球首个胃癌围术期靶免联合Ⅲ期研究重磅见刊JCO，恒瑞“双艾”组合再获认可

近日，上海交通大学医学院附属瑞金医院朱正纲教授作为PI的全国多中心研究协作组发起的“卡瑞利珠单抗联合阿帕替尼和化疗对比化疗治疗局部进展期胃癌”随机对照Ⅲ期试验(DRAGON-IV/AHEAD-G208[CAP 05]研究)重磅发表在肿瘤领域Top期刊《Journal of Clinical Oncology》(JCO，IF：42.1)上[1]。研究结果表明，卡瑞利珠单抗联合VEGFR2抑制剂阿帕替尼和SOX(奥沙利铂+替吉奥)对比SOX新辅助治疗可切除局部进展期胃癌，显著改善病理完全缓解(pCR)率。DRAGON-IV/AHEAD-G208研究是全球首个胃癌围术期靶免联合III期研究，这是该研究入选2023年欧洲肿瘤内科学会(ESMO)大会简短口头报告后，再次获国际医学界高度认可。 DRAGON-IV/AHEAD-G208研究在JCO发表 01 研究背景胃癌是一个严重的全球健康问题，2020年全球新发病例108.9万，死亡病例76.9万[2]。局部进展期胃或胃食管结合部腺癌围手术期推荐使用化疗，其中SOX方案(奥沙利铂+替吉奥)为首选，但围术期化疗疗效有限，仍有待提升[3,4]。卡瑞利珠单抗是恒瑞医药自主研发的一款人源化PD-1单克隆抗体，于2019年5月获国家药品监督管理局(NMPA)批准上市，目前已在中国获批9个适应症，涵盖肺癌、肝癌、食管癌、鼻咽癌以及淋巴瘤五大瘤种，为获批适应症和覆盖瘤种数量领先的国产PD-1产品。阿帕替尼是恒瑞医药开发的一款针对血管内皮生长因子受体(VEGFR)的小分子酪氨酸激酶抑制剂，于2014年10月获国家药品监督管理局(NMPA)批准上市。目前已在胃癌和肝癌领域获批三个适应症。卡瑞利珠单抗联合阿帕替尼(“双艾”组合)已在多个实体瘤中证实具有协同作用[5-8]。 DRAGON-IV/AHEAD-G208研究为一项多中心，随机对照、开放标签的Ⅲ期试验(NCT04208347)，旨在评估卡瑞利珠单抗联合阿帕替尼和化疗对比化疗在局部进展期胃或胃食管结合部腺癌围术期的疗效和安全性。 02 研究设计本研究招募临床分期为T3-4aN+M0，初治可切除胃癌或胃食管结合部腺癌患者，其中512例计划按1:1随机分配到SOXRC组(卡瑞利珠单抗+阿帕替尼+SOX)或SOX组。并根据原发灶部位(胃 vs. 胃食管结合部)和Bulky N(是 vs. 否)进行分层。患者术前分别接受3个周期的卡瑞利珠单抗+阿帕替尼+SOX或SOX，随后进行胃癌D2根治术。术后SOXRC组接受3个周期的卡瑞利珠单抗+阿帕替尼+SOX，和卡瑞利珠单抗+阿帕替尼维持治疗(卡瑞利珠单抗术前术后最多使用17个周期，阿帕替尼术前术后总治疗时长不超过一年)，SOX组进行3个周期的SOX，和S-1维持治疗(总治疗时长不超过一年)。主要终点包括盲态独立评审委员会(BIRC)评估的病理完全缓解(pCR，ypT0)率和研究者评估的无事件生存期(EFS)。次要终点包括总体病理完全缓解(tpCR)(ypT0N0)、主要病理缓解(MPR)、R0切除率、ypN分期、无病生存期(DFS)、总生存期(OS)和安全性。在SOXRC组和SOX组前360例随机患者有机会行D2根治术后进行pCR的主要分析。图1.研究设计 03 研究结果 1 基线及受试者分布 2019年12月18日至2022年12月31日期间，360例患者1：1被随机分配至SOXRC组(n=180)和SOX组(n=180)。两组基线特征平衡(表1)。截至2023年4月19日，SOXRC组179例接受新辅助治疗，164例完成新辅助治疗，155例接受手术。SOX组177例接受新辅助治疗，169例完成新辅助治疗，156例接受手术。截至数据截止时间，SOXRC组和SOX组仍各有51例、34例接受辅助治疗中(图2)。表1. 基线特征图2. 受试者分布 2 临床疗效在ITT人群中，BIRC评估的pCR率SOXRC组为18.3%(95% CI：13.0-24.8)，较SOX组5.0%(95% CI：2.3-9.3)显著提高13.7%(95% CI：7.2-20.1)(采用基于分层的Cochran Mantel Haenszel方法计算)，OR=4.5(95% CI：2.1-9.9)，p＜0.0001(图3)。 SOXRC组和SOX组MPR率分别为51.1%(95% CI：43.6-58.6)、37.8%(95% CI：30.7-45.3)，tpCR率分别为16.7%(95% CI：11.5-22.9)、4.4% (95% CI：1.9-8.6)(表2)。在所有亚组中观察到一致的pCR获益(图4)。 SOXRC组、SOX组手术完成率分别为86%(155/180)、87%(156/180)。在手术人群中，SOXRC组和SOX组pCR率分别为21.3%(95% CI：15.1-28.6)、5.8%(95% CI：2.7-10.7)。两组R0切除率分别为99%(153/155)、94%(147/156)。两组接受D2淋巴结清扫术的比例分别为96%(149/155)、97%(151/156)，中位淋巴结清扫数分别为32(范围：8-125)、29(范围：8-91)(表2)。图3. 主要研究终点pCR 图4. 亚组分析表2. 手术和术后病理结果 3 安全性分析整体安全性可控，且未影响手术可行性。 04 总结 DRAGON-IV/AHEAD-G208(CAP 05)研究是全球首个评估围术期免疫联合抗血管生成药物和化疗治疗可切除胃或胃食管结合部腺癌的III期临床研究。研究证实，卡瑞利珠单抗+阿帕替尼+SOX较SOX显著提高pCR率(18.3% vs. 5.0%)，主要终点之一pCR达成。整体安全性可控，且未影响手术可行性。EFS和OS仍在随访中。这项研究为胃癌围术期治疗提供了新的证据。卡瑞利珠单抗联合低剂量阿帕替尼和SOX有望作为可切除胃或胃食管结合部腺癌围术期治疗的新选择。参考文献： 1.Li C, Tian Y, Zheng Y, et al. Pathologic Response of Phase III Study: Perioperative Camrelizumab Plus Rivoceranib and Chemotherapy Versus Chemotherapy for Locally Advanced Gastric Cancer (DRAGON IV/CAP 05). J Clin Oncol. Published online October 9, 2024. doi:10.1200/JCO.24.00795 2.Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. 3.Zhang X, Liang H, Li Z, et al. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial [published correction appears in Lancet Oncol. 2021 Aug;22(8):e347. doi: 10.1016/S1470-2045(21)00417-4]. Lancet Oncol. 2021;22(8):1081-1092. 4.Yu J, Gao Y, Chen L, et al: Effect of S-1 plus oxaliplatin compared with fluorouracil, leucovorin plus oxaliplatin as perioperative chemotherapy for locally advanced, resectable gastric cancer: A randomized clinical trial. JAMA Netw Open 5:e220426, 2022 5.Cheng H, Zong L, Kong Y, et al. Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial. Lancet Oncol. 2021 Nov;22(11):1609-1617. 6.Meng X, Wu T, Hong Y, et al.Camrelizumab plus apatinib as second-line treatment for advanced oesophageal squamous cell carcinoma (CAP 02): a single-arm, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022 Mar;7(3):245-253. 7.Lan C, Shen J, Wang Y, et al. Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial. J Clin Oncol. 2020;38(34):4095-4106. 8.Qin S, Chan SL, Gu S, et al. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet. 2023;402(10408):1133-1146. 声明： 1.本新闻旨在发布医药前沿资讯，仅供医疗卫生专业人士参阅，非广告用途。 2.恒瑞医药不对任何药品和/或适应症作推荐。撰稿：肿瘤中央医学事务部排版：程梦真责编：李玉莹往期精选 | 研发创新 | 慢病创新里程碑！恒瑞首个自免创新药夫那奇珠单抗获批上市恒瑞医药新突破！中国首个自研阿片类镇痛创新药富马酸泰吉利定获批上市 | 国际化 | 海外BD再传捷报！恒瑞医药GLP-1类创新药组合实现海外许可恒瑞医药与默克达成合作，携手推进癌症创新疗法 | 重磅奖项 | 喜报！恒瑞医药荣获2023年度国家科技进步奖恒瑞医药连续六年入选全球制药企业50强榜单！ | 社会公益 | “健康中国行·重走长征路”项目启动仪式圆满举行！恒瑞提供公益支持，助力健康中国恒瑞医药集团向中国扶贫基金会捐赠3000万设立“健康帮扶基金”

临床3期上市批准临床结果

2024-10-22

·PMLiVE

Astellas’ Vyloy approved by FDA as first-line gastric cancer combination treatment

Astellas Pharma’s Vyloy (zolbetuximab-clzb) has been approved by the US Food and Drug Administration (FDA) as part of a first-line combination treatment for a subset of gastric cancer patients. The claudin 18.2-directed cytolytic antibody has been authorised for use alongside fluoropyrimidine- and platinum-containing chemotherapy to treat adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2-negative gastric or gastro-oesophageal junction (GEJ) adenocarcinoma whose tumours are claudin 18.2 positive. About 26,890 new cases of gastric cancer are expected to be diagnosed in the US this year and adenocarcinomas, which develop from cells in the innermost lining of the stomach, account for the majority of cases. The disease usually develops slowly over many years and early-stage symptoms frequently overlap with more common stomach-related conditions, causing most cases to go undetected until an advanced or metastatic stage. Vyloy now is the first and only claudin 18.2-targeted therapy to be approved in the US and was recently approved by the European Commission and UK Medicines and Healthcare products Regulatory Agency for the same patient population. Among the data supporting the FDA’s decision was results from the late-stage SPOTLIGHT trial, which assessed Vyloy plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) versus placebo plus mFOLFOX6. Median progression-free survival was 10.61 months with the Vyloy regimen compared to 8.67 months for placebo plus mFOLFOX6, while median overall survival was 18.23 months versus 15.54 months in the respective treatment groups. The approval was also informed by positive results from the phase 3 GLOW study, which evaluated Vyloy alongside CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin). Moitreyee Chatterjee-Kishore, senior vice president and head of immuno-oncology development at Astellas, said: “The approval of Vyloy as the first and only targeted therapy for CLDN18.2-positive patients in the US further delivers on our relentless pursuit of scientific progress for devastating diseases like gastric and GEJ cancers, which are often only discovered at the advanced stage.” Vyloy has also been approved in Japan and South Korea, and Astellas has submitted applications for the drug to regulatory agencies around the world.

上市批准临床结果临床3期免疫疗法抗体药物偶联物

100 项与左亚叶酸相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	左亚叶酸	V03AF04	DB11596

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
胃癌	中国	上海汇伦医药股份有限公司	2021-06-30
胃癌	中国	苏州第壹制药有限公司	2021-06-30
药物中毒	美国	Acrotech Biopharma LLC初创企业	2018-10-19
转移性结直肠癌	美国	Acrotech Biopharma LLC初创企业	2018-10-19
骨肉瘤	美国	Acrotech Biopharma LLC初创企业	2018-10-19
小肠癌	日本	Pfizer Inc.	2018-09-22
胰腺腺泡癌	日本	Pfizer Inc.	2013-12-20
结直肠癌	日本	Pfizer Inc.	2009-10-16
结直肠癌	瑞士	Pfizer Inc.	2009-10-16
肾肿瘤	日本	Pfizer Inc.	2009-10-16
毒性	日本	Pfizer Inc.	2005-12-31

未上市

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
毒性	临床2期	美国	Lederle Laboratories	1990-12-14
肝癌	临床申请批准	中国	上海汇伦医药股份有限公司	2023-07-06
胃癌	药物发现	日本	Takeda Pharmaceutical Co., Ltd.	2002-05-31

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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


NCT03528785 (NITRO, ESMO2023) 人工标引	临床2期	胰腺导管腺癌 TNF-α	107	Oxaliplatin+Irinotecan Liposomal +Levofolinic acid+5FU	(醖選餘醖廠鏇廠範願顧) = 壓鑰夢鹽顧構構淵淵簾憲憲遞餘壓襯觸遞襯糧 (鬱鹽鬱構艱觸夢艱範餘 ) 更多	积极	2023-10-23
NCT03528785 (NITRO, ESMO2023) 人工标引	临床2期	胰腺导管腺癌 TNF-α	107	Oxaliplatin+Irinotecan Liposomal +Levofolinic acid+5FU (resected patients)	(蓋窪鬱顧廠餘製糧鏇鑰) = 衊鏇鏇構鬱觸範衊壓範願繭鬱蓋製鬱齋築鑰製 (構願繭構艱蓋糧膚積淵, 12.6 ~ 34.1) 更多	积极	2023-10-23
NCT03528785 (nITRO, ASCO_GI2023) 人工标引	临床2期	胰腺导管腺癌	107	liposomal irinotecan 50 mg/m2 + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin 60 mg/m2	(淵餘選膚網夢選餘鏇顧) = 鏇壓膚鹹鬱廠鏇壓鑰蓋構範鑰簾憲構廠衊鹹構 (範衊蓋廠壓鬱簾鏇鹹繭 ) 更多	积极	2023-01-24
NCT03528785 (nITRO, ASCO_GI2023) 人工标引	临床2期	胰腺导管腺癌	107	liposomal irinotecan 50 mg/m2 + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin 60 mg/m2 (underwent resection)	(網鏇壓壓憲廠鹽憲膚範) = 餘願積鏇醖襯廠鏇顧壓膚積積鹹範鹽選構願廠 (構衊淵構壓齋齋製醖網 ) 更多	积极	2023-01-24
NCT01882868 (CTgov)	临床2期	结肠转移性腺癌 \| 转移性结直肠癌	62	aflibercept+Levofolinate+Irinotecan+5-FU	積顧夢窪構醖醖築積遞(網獵憲選齋構願壓窪窪) = 糧願鬱範顧範艱鏇觸憲鑰觸鹽艱齋壓範醖憲製 (築繭遞衊簾範構艱襯積, 膚齋衊觸憲憲窪範選襯 ~ 築窪網廠膚選襯窪壓築) 更多	-	2017-03-14
NCT01882868 (ASCO_GI2017) 人工标引	临床2期	转移性结直肠癌二线	62	5-fluorouracil+levofolinate+irinotecan+ziv-aflibercept	(夢鹽餘艱醖觸鏇鏇壓鑰) = 襯憲鹽鏇願壓繭積製膚窪鑰繭襯壓壓製衊鹽遞 (糧齋鹹餘構遞夢醖範衊, 1.3 ~ 15.3) 更多	不佳	2017-01-21
NCT01383707 (CTgov)	临床2期	结直肠癌肝转移 \| 转移性结直肠癌	77	Bevacizumab+Levofolinic acid+oxaliplatin+5-Fluorouracil (5-FU)	範淵醖壓繭餘築網簾窪(襯築憲鹽淵襯觸築壓觸) = 蓋淵構淵獵淵觸廠構範鏇繭鹽選夢蓋壓淵遞鏇 (壓醖鏇顧獵艱構築簾夢, 膚顧鹹範衊鑰遞選憲艱 ~ 遞網醖鹽繭膚獵淵鑰鏇) 更多	-	2016-09-07
UMIN000004958 (JASPAC 03, UEGW2013)	临床2期	胰腺癌一线	32	S-1 plus Leucovorin	(顧繭夢糧願觸構鏇夢觸) = 鹽鹽願窪壓構簾窪壓繭築繭糧鑰鬱鹹鏇襯淵網 (鑰齋糧憲蓋鏇範艱製積, 10.5 ~ 31.5) 更多	不佳	2013-10-01
NCT00865709 (RESPECT, CTgov)	临床2期	转移性结直肠癌	198	Sorafenib (Nexavar, BAY43-9006)+levo-leucovorin+oxaliplatin+5-FU (Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6)	積觸遞鏇鏇艱餘築遞構(築糧範醖淵鹽夢獵範蓋) = 觸鏇積鹹觸夢網顧憲艱網鹽範積壓糧繭夢簾鏇 (衊夢衊糧衊廠餘製齋鏇, 鑰鑰網醖醖鹹範憲憲壓 ~ 齋齋製網餘壓憲蓋襯壓) 更多	-	2012-03-20
NCT00865709 (RESPECT, CTgov)	临床2期	转移性结直肠癌	198	levo-leucovorin+oxaliplatin+5-FU (Matching Placebo + mFOLFOX6)	積觸遞鏇鏇艱餘築遞構(築糧範醖淵鹽夢獵範蓋) = 淵獵選餘窪築鑰簾醖鹽網鹽範積壓糧繭夢簾鏇 (衊夢衊糧衊廠餘製齋鏇, 簾夢構鹽鏇選觸艱願鏇 ~ 廠積顧鑰鹹選獵鬱壓顧) 更多	-	2012-03-20
C96.1 (ASCO2009)	临床3期	结肠癌	-	l form of folinic acid	壓顧選願蓋糧淵觸簾餘(鬱觸鏇築簾鬱衊鹹製繭) = 顧餘醖鏇鬱壓鹹繭襯餘廠網構鑰遞鹹夢鏇願廠 (繭襯襯淵遞繭夢糧願範 ) 更多	-	2009-05-20
C96.1 (ASCO2009)	临床3期	结肠癌	-	dl form of folinic acid	壓顧選願蓋糧淵觸簾餘(鬱觸鏇築簾鬱衊鹹製繭) = 鹹鹹網窪鬱蓋獵範窪餘廠網構鑰遞鹹夢鏇願廠 (繭襯襯淵遞繭夢糧願範 ) 更多	-	2009-05-20
ASCO2004	临床2期	转移性去势抵抗性前列腺癌	44	Oral Tegafur (Fluorouracil) + Levofolinic Acid + Megestrol Acetate	(鏇獵廠鏇衊選壓積鏇醖) = 鹹膚範鏇醖構餘窪夢選繭艱範壓簾齋醖選鬱蓋 (選餘壓鬱獵鬱醖觸膚齋 )	-	2004-07-15
ASTRO2001	N/A	局部晚期直肠癌	-	Capecitabine + Leucovorin	選襯蓋構鑰選壓糧觸憲(憲齋廠鹹築範窪艱醖憲) = 3% 範範膚構願製鬱繭鑰願 (簾繭窪鹽獵鑰顧襯築顧 ) 更多	-	2001-11-01