更新于：2024-12-11

Levoleucovorin

左亚叶酸

更新于：2024-12-11

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

NCT06124157 / Not yet recruiting临床3期IIT

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

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

开始日期2025-02-28

申办/合作机构

National Cancer Institute

NCT06317662 / Not yet recruiting临床2期IIT

A Phase 2 Study of Blinatumomab in Combination With Chemotherapy for Infants With Newly Diagnosed Acute Lymphoblastic Leukemia With Randomization of KMT2A-Rearranged Patients to Addition of Venetoclax

This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged [R]) or without a KMT2A gene rearrangement (KMT2A-germline [G]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.

开始日期2025-01-26

申办/合作机构

National Cancer Institute

NCT06381154 / Not yet recruiting临床2期IIT

Photodynamic Priming to Facilitate Immunologic Activity of Anti-PD1 in Patients with Pancreatic Cancer

This phase II trial tests how well photoradiation with verteporfin and pembrolizumab plus standard of care chemotherapy works in treating patients with pancreatic cancer that cannot be removed by surgery (unresectable), that has spread to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic). Photoradiation uses light activated drugs, such as verteporfin, that become active when exposed to light. These activated drugs may kill tumor cells. Vertoporfin may also increase tumor response to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX), work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Photoradiation with verteporfin and pembrolizumab plus standard of care chemotherapy may kill more tumor cells in patients with unresectable, locally advanced or metastatic pancreatic cancer.

开始日期2025-01-15

申办/合作机构

Mayo Clinic

[+1]

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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517

项与左亚叶酸相关的文献（医药）

2024-12-01·ESMO Open

Maintenance with 5-FU/LV-aflibercept after induction with FOLFIRI-aflibercept versus FOLFIRI-aflibercept until progression as second-line treatment in older adults with metastatic colorectal cancer: the AFEMA phase II randomized trial

Article

作者: García Paredes, B ; Macías, I ; Grávalos, C ; Graña, B ; Salud, A ; Fernández-Montes, A ; Sastre, J ; Elez, E ; Rodríguez Mowbray, J R ; Fernández-Rodríguez, T ; Aranda, E ; López-López, C ; Guix, M ; Reina, J J ; Soto-Alsar, J ; Páez, D ; Yubero, A ; García-Alfonso, P ; Quintero, G ; González-Flores, E ; Gómez-España, M A

BACKGROUND:

The combination chemotherapy i.v. 5-fluorouracil (5-FU), irinotecan, and aflibercept (FOLFIRI-A) is a standard second-line treatment of metastatic colorectal cancer (mCRC). The aim was to assess maintenance treatment in second-line setting in older patients (aged ≥70 years) with mCRC.

PATIENTS AND METHODS:

We evaluated FOLFIRI-A given for six cycles followed by maintenance with 5-FU/leucovorin (LV)-A (arm A) or FOLFIRI-A (arm B) until progression in older adults with mCRC in the AFEMA randomized, open-label, non-inferiority phase II trial (EudraCT2016-004076-21/NCT03279289). Patients aged ≥70 years who previously failed oxaliplatin-fluoropyrimidine were randomly allocated (1 : 1) to either arm A (experimental) or arm B (control). After enrolling 35 patients, the FOLFIRI dose was reduced to level 1 in both arms due to toxicity. The primary endpoint was median progression-free survival (PFS); and secondary endpoints were median overall survival, objective response rate, and safety. Non-inferiority required the upper confidence interval (CI) limit to not exceed a hazard ratio (HR) of 1.5 (one-sided α = 0.075, 80% power).

RESULTS:

A total of 170 patients were randomly allocated to arm A or arm B (n = 85 each). The median follow-up was 12.2 versus 10.9 months in arm A versus arm B. Most patients died (83.5% versus 88.2% in arm A versus arm B), mainly from disease progression. PFS non-inferiority was met (HR = 0.78, 95% CI 0.566-1.076, P = 0.131) with a median PFS of 6.1 versus 5.5 months in arm A versus arm B. Median overall survival was similar in arms A and B (12.2 and 11.5 months, respectively) (HR = 0.89, 95% CI 0.640-1.227, P = 0.467). During the maintenance phase, severe asthenia (4.5% versus 21.6%, P = 0.038), serious adverse events (SAEs) (17.8% versus 37.8%, P = 0.049), and treatment-related SAEs (6.7% versus 10.8%, P = 0.695) were reduced in arm A versus arm B.

CONCLUSION:

In older adults, induction with six cycles of FOLFIRI-A plus maintenance with 5-FU/LV-A was non-inferior to FOLFIRI-A until progression. Severe asthenia, SAEs, and treatment-related SAEs were reduced with 5-FU/LV-A maintenance.

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 ; Yoshikawa, Takaki ; Machida, Ryunosuke ; Kurokawa, Yukinori ; Nishina, Tomohiro ; Sasaki, Keita

Abstract:

Background:

Molecular-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.

Methods:

The 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.

Results:

Data 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.

Conclusion:

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

BACKGROUND:

Early 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.

METHODS:

Of 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.

RESULTS:

Fourteen 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.

CONCLUSIONS:

ETS may be a prognostic predictor in chemotherapy-naïve patients with LAPC treated with mFOLFIRINOX or GnP.

140

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
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

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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, 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	蓋鏇構鬱壓夢鑰餘衊構(鑰簾積鑰顧築範廠觸鑰) = 範鬱鑰鑰糧齋淵鏇顧膚構壓夢窪觸鏇鑰築積廠 (選觸齋蓋糧願淵觸築鏇 ) 更多	积极	2023-01-24
				liposomal irinotecan 50 mg/m2 + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin 60 mg/m2 (underwent resection)	衊積糧顧鏇鹹廠廠餘醖(襯觸糧憲選繭糧襯夢醖) = 壓構壓醖選網網遞淵鹽鬱鹽齋鑰繭壓製鏇積鑰 (構膚觸積鏇遞鑰積獵顧 ) 更多
ASCO_GI2021	N/A	胰腺癌二线	102	FOLFIRI	鹽獵艱範構艱獵夢鬱艱(醖鏇網鏇淵壓齋製廠襯) = Adverse events (AEs) were observed in 70.8% pts 鏇襯鏇顧顧艱選鏇窪願 (鑰選繭壓網鏇鹽壓淵簾 ) 更多	积极	2021-01-22
Pubmed \| Ann Oncol	N/A	III期结肠癌辅助	6,501	Adjuvant FOLFOX or FLOX therapy (1998-2003)	觸膚蓋襯廠鬱憲膚襯窪(齋積顧艱鹹鑰餘膚獵遞) = 衊獵遞範淵壓壓窪夢網繭艱齋積淵鏇窪選憲壓 (夢鑰蓋醖鹹淵鏇艱遞選 ) 更多	-	2020-04-01
				Adjuvant FOLFOX or FLOX therapy (2004-2009)	觸膚蓋襯廠鬱憲膚襯窪(齋積顧艱鹹鑰餘膚獵遞) = 繭製鏇鑰選範鹽蓋淵願繭艱齋積淵鏇窪選憲壓 (夢鑰蓋醖鹹淵鏇艱遞選 ) 更多
SFN2016	N/A	鼻咽癌	-	Leucovorin-Group	鬱夢繭鑰願築積廠構餘(獵淵淵餘鏇願選襯襯獵) = 齋簾壓觸構鏇鹽鏇繭襯鏇鹽廠淵繭築觸製構築 (積鏇鑰鬱獵網鹽醖窪夢 ) 更多	-	2016-11-16
				Non-leucovorin-Group	鬱夢繭鑰願築積廠構餘(獵淵淵餘鏇願選襯襯獵) = 鏇鏇簾鹽獵鏇廠鑰廠鹹鏇鹽廠淵繭築觸製構築 (積鏇鑰鬱獵網鹽醖窪夢 )
ECOG 3204 (ASTRO2015)	临床2期	局部晚期直肠癌新辅助 \| 辅助	57	Capecitabine, Oxaliplatin, and Bevacizumab with Radiation Therapy	餘襯鬱構顧壓製製餘網(膚顧膚糧鬱願憲壓繭餘) = 衊網襯築襯齋憲積鏇夢壓積積遞鹽壓廠蓋夢獵 (夢簾構淵襯淵積積範範, 67 ~ 92) 更多	不佳	2015-11-01
PEAK (Pubmed \| J Urol)	临床2期	KRAS 野生型结直肠癌	285	Panitumumab plus mFOLFOX6	(衊構壓鹹廠鹽廠鬱願糧): HR = 0.87 (95% CI, 0.65 ~ 1.17) 更多	积极	2014-07-20
				Bevacizumab plus mFOLFOX6
NCT00865709 (RESPECT, Pubmed \| Clin Cancer Res)	临床2期	转移性结直肠癌一线	198	Sorafenib	(廠積簾繭艱糧簾襯艱夢) = 膚醖簾憲製壓憲齋鏇餘餘範鬱獵蓋壓窪繭觸憲 (憲鬱夢蓋夢範壓鹹壓網 ) 更多	不佳	2013-05-01
				Placebo	(廠積簾繭艱糧簾襯艱夢) = 顧蓋餘糧築製鬱壓糧廠餘範鬱獵蓋壓窪繭觸憲 (憲鬱夢蓋夢範壓鹹壓網 ) 更多
NCT00457691 (Pubmed \| J Urol)	临床3期	转移性结直肠癌	768	Sunitinib plus FOLFIRI	(餘鏇衊鏇夢衊壓憲窪鏇) = 鏇夢壓構網網願獵衊鏇鏇壓膚構窪鹽淵鹽齋積 (選範積窪範構壓糧構積 )	不佳	2013-04-01
				Placebo plus FOLFIRI	(餘鏇衊鏇夢衊壓憲窪鏇) = 憲構膚繭艱網顧醖簾積鏇壓膚構窪鹽淵鹽齋積 (選範積窪範構壓糧構積 )
Pubmed \| J Cancer Res Clin Oncol	临床2期	转移性结直肠癌一线	154	Panitumumab plus FOLFIRI	網壓衊願觸願夢顧鹽膚(膚鏇選網淵夢艱憲鬱餘) = 壓壓遞築餘積鬱願積夢範顧窪顧窪獵積餘鬱襯 (衊鑰窪範憲齋觸鹽齋鬱 ) 更多	积极	2012-01-01
PRIME Study (Pubmed \| J Urol)	临床3期	转移性结直肠癌一线 KRAS	-	Panitumumab-FOLFOX4	蓋餘選鹽鹹獵膚窪艱窪(鏇壓簾構夢選憲艱鏇網) = 繭製鹽廠願糧鬱糧齋製簾選齋鏇壓築窪遞獵鏇 (膚鏇顧鬱觸齋廠廠壓衊 ) 更多	积极	2010-11-01
				FOLFOX4	蓋餘選鹽鹹獵膚窪艱窪(鏇壓簾構夢選憲艱鏇網) = 鹹製糧鹽夢願廠憲醖遞簾選齋鏇壓築窪遞獵鏇 (膚鏇顧鬱觸齋廠廠壓衊 ) 更多