甲磺酸仑伐替尼(Lenvatinib mesylate) - 药物靶点：FGFR1 x FGFR2 x FGFR3 x FGFR4 x PDGFRα x RET x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit_在研适应症：晚期子宫内膜癌，复发性子宫内膜癌，胸腺肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

lenvatinib、lenvatinib mesilate、Lenvatinib mesilate (JAN)

+ [19]

靶点

FGFR1 x FGFR2 x FGFR3 x FGFR4 x PDGFRα x RET x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit

作用方式

拮抗剂、抑制剂

作用机制

FGFR1拮抗剂(成纤维细胞生长因子受体-1拮抗剂)、FGFR2拮抗剂(成纤维细胞生长因子受体-2拮抗剂)、FGFR3拮抗剂(成纤维细胞生长因子受体-3拮抗剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [11]

在研适应症

晚期子宫内膜癌复发性子宫内膜癌胸腺肿瘤+ [97]

非在研适应症

晚期乳腺癌晚期胃癌甲状腺未分化癌+ [31]

原研机构

Eisai Co., Ltd.

在研机构

Merck Sharp & Dohme Corp.

Eisai Co., Ltd.

Eisai Europe Ltd.

+ [6]

非在研机构

Bristol Myers Squibb Co.

Merck & Co., Inc.

江苏康宁杰瑞生物制药有限公司

+ [1]

权益机构

Biotoscana Investments SA

Merck & Co., Inc.

Novartis AG

+ [3]

最高研发阶段批准上市

首次获批日期

美国 (2015-02-13),

甲状腺癌

最高研发阶段(中国)批准上市

特殊审评突破性疗法 (美国)、加速批准 (美国)、孤儿药 (美国)、优先审评 (中国)、附条件批准 (中国)、孤儿药 (日本)、优先审评 (澳大利亚)、孤儿药 (澳大利亚)、特殊审批 (中国)

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结构/序列

分子式C22H23ClN4O7S

InChIKeyHWLFIUUAYLEFCT-UHFFFAOYSA-N

CAS号857890-39-2

关联

745

项与甲磺酸仑伐替尼相关的临床试验

NCT05077215

/ Not yet recruiting临床3期

A Phase 3, Randomized, Open-Label, Active-Controlled, Superiority Trial of EG007, Added to the Combination of Lenvatinib Plus Pembrolizumab vs. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer

This is a Phase 3, multicenter, randomized, open-label trial to evaluate whether EG-007 plus Len+Pem is superior to Len+Pem alone in patients with advanced endometrial cancer (Stage III or IV). This trial will be preceded by a safety lead-in study with up to 28 patients (the safety lead-in is a separate, free-standing protocol).
Approximately 450 patients will be randomized equally (1:1) to receive EG-007 plus Len+Pem or Len+Pem alone. The randomization will be stratified by the following stratification factors:
* Diagnosis Classification (advanced Stage III/IV vs. recurrent endometrial cancer)
* ECOG score at baseline (0 vs 1)
* Geographic region (Asia vs ROW)

开始日期2026-12-01

申办/合作机构

Evergreen Therapeutics, Inc

NCT07460206

/ Not yet recruiting临床2期IIT

Pembrolizumab Plus Lenvatinib in REcurrent ccRCC Patients Failing permbroLizUmab aDjuvant trEatment - PRELUDE Study

This study is being performed as a single-arm open-label study in order to provide information on the potential benefits of the combination of pembrolizumab and lenvatinib in participants with advanced ccRCC who have progressed on Pembrolizumab as their prior therapy in the adjuvant RCC setting.

开始日期2026-08-01

申办/合作机构-

NCT05106127

/ Not yet recruiting临床2期

A Phase 2, Open-Label, Safety Lead-In With Long Term Safety Study of EG-007, Added to the Combination of Lenvatinib Plus Pembrolizumab

This is a Phase 2 trial Safety Lead-in trial conducted in 3 cohorts of patients.
A safety lead-in study of the impact of adding the Repurposed Drugs a third agent will be conducted prior to opening enrollment into the compassionate use study. All patients enrolled in the safety lead-in study may continue long-term treatment under this protocol without interruption of dosing.

开始日期2026-08-01

申办/合作机构

Evergreen Therapeutics, Inc

100 项与甲磺酸仑伐替尼相关的临床结果

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100 项与甲磺酸仑伐替尼相关的转化医学

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100 项与甲磺酸仑伐替尼相关的专利（医药）

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3,231

项与甲磺酸仑伐替尼相关的文献（医药）

2026-12-31·ANNALS OF MEDICINE

Systematic meta-analysis of the toxicities and side effects of the targeted drug lenvatinib

Review

作者: Liu, Huihui ; Cui, Chao ; Wang, Kai ; Li, Qingwei ; Sun, Yu ; Gao, Shuai ; Shi, Jingfei

BACKGROUND:

Lenvatinib, an effective targeted drug for various cancers, has clinical medication safety concerns due to its toxicities and side effects.

OBJECTIVE:

This study evaluated lenvatinib-induced any adverse events (any AEs) and nine aspects: vascular toxicities related to the circulatory system (vascular toxicities, blood system, and heart), toxicities of the skin and its appendages (skin/subcutaneous tissue and taste system), toxicities of the respiratory system (respiratory, thoracic, and mediastinal and respiratory tract), toxicities of the nervous system (nervous system and general), toxicities of the digestive system (gastrointestinal and liver), toxicities of the urinary system, toxicities of the endocrine and metabolic system (endocrine and metabolism/nutrition), toxicities of the musculoskeletal system, and other severe toxicities. Toxicities and side effects were stratified by severity into any and ≥3 grades for analysis.

PATIENTS/MATERIALS AND METHODS:

Multiple databases were searched for lenvatinib cancer clinical studies (cohort studies and randomized controlled trials) from inception to December 31, 2024; toxicity and side effect data were extracted and analyzed.

RESULTS:

Nine high-quality studies were included, showing that lenvatinib is effective in cancers but has notable toxicities. Taking hypertension as an example, for any grade, the risk ratio (RR) was 2.34 with a 95% confidence interval (CI) of [2.09, 2.62], a Z-value of 14.74, and a P-value <0.00001; for grade ≥3, the RR was 2.60 with a 95% CI of [2.21, 3.06], a Z-value of 11.44, and a P-value <0.00001.

CONCLUSION:

Lenvatinib is effective for cancer but toxic, and this study supports its rational clinical use.

2026-12-31·CANCER BIOLOGY & THERAPY

Lenvatinib potentiates the antitumor efficacy of combined radiotherapy and PD-L1 blockade in lung adenocarcinoma

Article

作者: Li, Tao ; Zhang, Shichuan ; Zhang, Xue ; Xiao, Ling ; Li, Linjie ; Tang, Chengxi ; Lyu, Jiahua ; Liu, Yudi ; Nie, Xinyu ; Huang, Jianming

BACKGROUND:

The potential of Lenvatinib to synergize with combined radiotherapy and immunotherapy in LUAD remains incompletely characterized.

METHODS:

We investigated Lenvatinib's effects on radiation-induced PD-L1 in LUAD cells and VEGFR2 in HUVECs via Western blot, VEGFA expression via RT-qPCR/ELISA, and angiogenesis via immunofluorescence. LUAD-HUVEC crosstalk was modeled in vitro. In C57BL/6 mice bearing LUAD tumors, we evaluated the efficacy of RT and anti-PD-L1 with or without Lenvatinib, monitoring tumor growth, survival, and profiling the tumor microenvironment by mIHC and flow cytometry.

RESULTS:

Lenvatinib suppressed radiation-induced PD-L1 and VEGFR2 expression, inhibited angiogenesis, and disrupted HUVEC-facilitated LUAD proliferation. The triple-combination (RT + anti-PD-L1 + Lenvatinib) significantly suppressed tumor progression (P < 0.05) and extended median survival (34 vs. 29.5 days, P < 0.05) versus dual therapy. It also enhanced intratumoral CD8⁺ T-cell infiltration and cytotoxicity, promoted M1-like macrophage polarization, and reduced regulatory T cell frequency and microvessel density.

CONCLUSIONS:

Lenvatinib potentiates RT and anti-PD-L1 therapy in LUAD through dual immune-vascular modulation, supporting the clinical translation of this triple-combination strategy.

2026-12-01·JOURNAL OF MOLECULAR MEDICINE-JMM

Combined targeting poly (ADP-ribose) polymerase and receptor tyrosine kinase inhibits ovarian clear cell carcinoma progression through disrupted ribosome biogenesis

Article

作者: Lai, Chyong-Huey ; Chao, Angel ; Fu, Chiung-Hui ; Chao, An-Shine ; Yu, Alice L ; Teng, Yu-Chuan ; Wu, Ren-Chin ; Huang, Ruby Yun-Ju ; Lin, Chiao-Yun

OCCC has extremely poor prognosis. ARID1A mutation-related chromatin remodeling errors are key molecular features of OCCC. Dysregulation of receptor tyrosine kinases-related signaling pathways is common in OCCC. Here we show that combination of niraparib and lenvatinib exhibits significant synergistic inhibitory effects against platinum-resistant OCCC cell lines, xenografts, patient-derived tumoroid (PDT) models, and prolonged survival in the platinum-refractory patient-derived xenograft (PDX) model. RNA-sequencing revealed the most differently expressed genes in PDX treated with a combination of niraparib and lenvatinib versus control were in structural ribosomal components. Selected differently expressed ribosomal proteins (RPs: RPS2, RPS5, RPS9, and RPL3) was validated using quantitative polymerase chain reaction. Nucleophosmin (NPM1) expression, which is involved in ribosome biogenesis, was inhibited by niraparib and lenvatinib. Our findings imply that combined niraparib and lenvatinib reduces platinum-resistant OCCC progression by attenuating Src phosphorylation, NPM1 expression and ribosome biogenesis. These results highlight the necessity for continued exploration of this promising treatment strategy, particularly in future clinical trials for platinum-resistant or platinum-refractory OCCC. KEY MESSAGES: The combination of niraparib and lenvatinib synergistically inhibits platinum-resistant OCCC. This combination prolongs survival in a platinum-refractory PDX model. RNA sequencing revealed that the most differentially expressed genes in PDX models treated with this combination were associated with structural ribosomal components. This combination suppresses Src phosphorylation, NPM1 expression, and ribosomal protein levels in OCCC.

1,721

项与甲磺酸仑伐替尼相关的新闻（医药）

2026-04-02

·FiercePharma

Another AstraZeneca Emerald glimmers as Imfinzi, Imjudo delay liver cancer progression

The Emerald-3 showing draws a resemblance to AstraZeneca’s Emerald-1 readout in the same locoregional treatment setting among liver cancer patients eligible for TACE. Another green light appears increasingly within reach for AstraZeneca’s Emerald program after a combo regimen featuring the company’s immunotherapy duo, Imfinzi and Imjudo, showed benefit in certain liver cancer patients. Results from the phase 3 Emerald-3 trial showed that the combination, paired with transarterial chemoembolizaton (TACE) and Lenvima, significantly improved progression-free survival (PFS) versus TACE alone in patients with unresectable locoregional hepatocellular carcinoma. Lenvima is a multikinase inhibitor sold by Merck & Co. and Eisai.But whether AZ has struck gold with Emerald-3 remains to be seen. Overall survival (OS), a secondary endpoint that will be a key consideration for the FDA, was immature at the interim analysis, although AZ highlighted a trend toward improvement in its April 2 announcement. In two ways, the Emerald-3 showing draws a resemblance to AZ’s Emerald-1 readout in the same locoregional treatment setting among liver cancer patients eligible for TACE. Two years ago, the Emerald-1 trial hit its primary endpoint, showing that a cocktail of Imfinzi, Avastin and TACE reduced the risk of progression or death by 23% versus TACE alone. At that time, OS was also immature, and AZ’s oncology R&D chief, Susan Galbraith, Ph.D., flagged that patient survival data are crucial in this locoregional setting. Case in point: Despite a PFS win, Merck & Co. last year abandoned hopes for a similar liver cancer approval for its Keytruda-Lenvima-TACE regimen after it failed to improve OS compared with TACE alone.Emerald-1 still hasn’t reported its final OS data, and the study has not graduated to the regulatory submission batch in AZ’s most recent earnings report in February. In addition, like Emerald-1, Emerald-3 has a second experimental arm. In this cohort, Imfinzi, Imjudo and TACE—without Lenvima—showed what AZ called “strong trends” toward improved PFS and OS, although these analyses were not formally tested. Previously, in Emerald-1, only the Avastin-containing triplet beat TACE, while Imfinzi-TACE failed to move the needle. AZ is discussing the latest Emerald-3 data with global regulatory authorities while waiting for final results from the trial’s key secondary endpoints, Galbraith said in an April 2 statement.As for Emerald-1, an AZ spokesperson said the company will share additional data in the future and will update its regulatory discussion plans as appropriate. Liver cancer helped AZ’s CTLA-4 agent Imjudo break into the market in 2022 as part of a combination with Imfinzi in unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer. Patients who are eligible for embolization have an earlier stage of disease. In 2026, more than 200,000 patients belong to this category, according to data cited by AZ—however, most patients who receive the procedure experience progression or recurrence within six to ten months.The British pharma also has a third Emerald. Called Emerald-2, the phase 3 study is testing Imfinzi with Avastin in adjuvant liver cancer, with its data expected in the second half of 2026. As for the Imfinzi-Imjudo duo, AZ also expects readouts this year from its Nile trial in first-line metastatic bladder cancer and from its Volga study assessing a neoadjuvant regimen in cisplatin-ineligible muscle-invasive bladder cancer. Both will need to live up to the high expectations set by the combination of Merck & Co.’s Keytruda and Pfizer and Astellas’ antibody-drug conjugate Padcev.For AZ’s broader oncology portfolio, the company is bracing for an upcoming FDA advisory committee meeting that will dig into two separate applications for its oral SERD med camizestrant and the AKT inhibitor Truqap. The high-stakes first-line non-small cell lung cancer readout for Daiichi Sankyo-partnered Datroway from the Avanzar trial is also expected this year.

临床3期临床结果抗体药物偶联物临床2期

2026-04-02

·毕凯今选

【前沿精粹 318】肠道微生物组：肝细胞癌的新兴精准医学生物标志物

肠道微生物组：肝细胞癌的新兴精准医学生物标志物引言引言近年来，肿瘤免疫治疗的飞速进展让“免疫检查点抑制剂”成为晚期肝癌患者最重要的生命线之一。然而，临床现实依旧严峻：即便采用标准联合方案，也仅有三成左右的患者能够获得持久缓解，七成患者在数月内出现继发耐药。面对这一瓶颈，科学家开始把目光投向人体内部一个被长期忽视却潜力巨大的“隐形器官”——肠道微生物组。过去十年，从黑色素瘤到非小细胞肺癌，越来越多的证据表明，肠道菌群的组成与免疫治疗的成败密切相关。本综述首次系统梳理了菌群-免疫-肝细胞癌三者之间的复杂网络，并明确提出“肠道微生物组可作为HCC精准医学的全新生物标志物”这一概念。从“肠-肝轴”说起：肝脏为何始终与肠道“对话” 解剖学上，肝脏通过门静脉直接收集来自肠道的血液，每天处理超过七成以上经肠道吸收的营养、毒素以及细菌代谢产物。因此，肝脏与肠道之间形成了独特的“门静脉-胆道-循环”双向通道，即所谓的“肠-肝轴”。在正常生理状态下，该轴维持着免疫耐受与免疫激活的精妙平衡：一方面，肝脏需要抑制对食物抗原和共生菌的过度反应，避免慢性炎症；另一方面，当病原体或肿瘤细胞出现时，肝脏又必须迅速启动免疫杀伤。肠道菌群通过分泌短链脂肪酸、次级胆汁酸、胞外多糖以及脂多糖等活性分子，沿着门静脉进入肝脏，直接调控库普弗细胞、肝窦内皮细胞、胆管上皮细胞和多种淋巴细胞的功能。一旦菌群失衡，这种双向对话就会被打破，肝脏免疫微环境随之倾斜，为肝细胞癌的发生、进展以及治疗抵抗埋下伏笔。免疫检查点抑制剂为何“有人欢喜有人愁目前，晚期HCC的一线标准治疗包括阿替利珠单抗联合贝伐珠单抗，以及度伐利尤单抗联合曲美木单抗。两种方案均依赖于PD-1/PD-L1或CTLA-4通路的阻断，从而唤醒T细胞对肿瘤的杀伤。然而，临床观察发现，同样病理类型、同样分期的患者，疗效却天差地别：部分患者肿瘤几乎完全消退，而另一部分患者病灶纹丝不动，甚至快速进展。传统生物标志物如PD-L1表达、肿瘤突变负荷、甲胎蛋白水平等，均无法稳定预测疗效。于是，研究者开始怀疑：是否体内另一套“基因组”——微生物组，在幕后左右着免疫治疗的成败？菌群“指纹”决定疗效：来自HCC人群的多中心证据过去五年，全球多个团队对接受PD-1抑制剂单药或联合治疗的HCC患者进行了粪便宏基因组纵向采集。中国台湾团队对8例接受卡瑞利珠单抗治疗的HBV-HCC患者进行动态测序发现，应答者基线菌群中就富集阿克曼氏菌、瘤胃球菌科等“好菌”，而无效者则出现变形菌门门特别是大肠杆菌的过度生长。更令人振奋的是，当把应答者的粪便移植到无菌小鼠体内后，小鼠皮下移植瘤对PD-1阻断的敏感性显著增强，肿瘤浸润CD8+T细胞比例明显升高，提示菌群不仅关联疗效，更可主动“传递”抗肿瘤免疫力。意大利一项11例小样本研究进一步证实，阿克曼氏菌和双歧杆菌的丰度与无进展生存期呈正相关，而肠杆菌科及粪便钙卫蛋白水平升高则提示原发耐药。来自上海交通大学的Wu团队对35例不可切除HCC患者进行三个月纵向跟踪，结合16S rRNA测序与血清代谢组学，发现粪杆菌属、瘤胃球菌属以及α-D-葡萄糖水平可作为联合预测因子，其机器学习模型预测客观缓解的AUC高达0.87，显著优于单一菌群或代谢物指标。这些研究共同指向一个结论：HCC患者肠道菌群的“指纹”可在治疗前即给出免疫治疗是否有效的“参考答案”。机制解码：菌群如何“遥控”肝脏免疫微环境 1. 免疫细胞的“招募令”：阿克曼氏菌可刺激树突状细胞分泌IL-12，进而招募CXCR3+CD4+T细胞与CD8+T细胞进入肿瘤床，增强对肿瘤抗原的识别与杀伤。 2. 短链脂肪酸的“双重调控”：丁酸、丙酸等SCFA一方面通过组蛋白去乙酰化酶抑制效应，促进Foxp3+调节性T细胞分化，维持外周耐受；另一方面，丁酸可增强CD8+T细胞受体信号，上调颗粒酶B与IFN-γ分泌，直接强化抗肿瘤免疫。 3. 胆汁酸“信号转导”：共生菌携带的胆盐水解酶(BSH)把肝脏分泌的初级胆汁酸转化为次级胆汁酸，后者通过激活FXR与TGR5受体，抑制NLRP3炎症小体，减少肝脏慢性炎症，同时促进NK细胞表达CXCR6，使其在肝窦内富集，形成免疫监视“哨兵网络”。 4. 肠屏障“防火墙”：菌群紊乱导致黏液层变薄、紧密连接蛋白下调，LPS等病原相关分子模式易位至门静脉，激活肝脏Kupffer细胞TLR4-NF-κB通路，诱导IL-6、TNF-α持续释放，造成免疫抑制性髓系细胞扩增，最终形成“冷肿瘤”微环境，令PD-1抗体无的放矢。图1 肠道微生物组在肝细胞癌免疫治疗疗效预测与调控中的作用。该图突出了肠-肝之间的解剖连接及双向互作。尽管本综述主要聚焦于肠道对肝脏免疫、肿瘤微环境及治疗反应的影响，但肝-肠方向的反向信号通路(例如通过初级胆汁酸)亦被承认，唯文中未予详述。药物代谢的“隐形之手” 除了免疫调控，菌群还通过两条路径干预HCC常用药物的代谢。一是“直接代谢”：菌酶可水解伊立替康的葡萄糖醛酸结合物SN-38-G，重新释放具有肠道毒性的活性SN-38，导致患者严重腹泻，限制剂量提升。二是“间接调控”：菌群代谢产物丁酸、丙酸可上调或下调肝脏细胞色素P450酶系(如CYP1A1、CYP3A4)以及UDP-葡萄糖醛酸转移酶的表达，从而改变靶向药索拉非尼、仑伐替尼以及免疫检查点抑制剂的血药浓度。临床回顾性研究提示，接受广谱抗生素治疗的HCC患者，其索拉非尼相关无进展生存期显著缩短，可能与菌群被抑制后CYP3A4活性下降、药物清除率降低有关。由此可见，菌群不仅决定免疫治疗是否起效，也影响靶向药物是否毒副难当。从“生物标志物”到“治疗武器”：菌群干预策略 1. 粪菌移植(FMT) FMT最早用于难治性艰难梭菌感染，如今在肿瘤领域也崭露头角。2021年，《Science》同期发表的两项I期研究证实，将PD-1抗体应答者的粪便经结肠镜移植给耐药黑色素瘤患者后，再联合抗PD-1治疗，客观缓解率提升至65%，且未增加3级以上免疫毒性。针对HCC，欧洲已启动两项探索性临床研究：奥地利的FAB-HCC研究拟招募12例经一线免疫联合治疗失败的晚期患者，接受应答者来源的冻干粪菌胶囊联合阿替利珠单抗+贝伐珠单抗，主要终点为安全性与肠道免疫微环境变化；德国的FLORA研究则重点评估FMT能否提升肿瘤CD8T细胞浸润。虽然结果尚未公布，但FMT在HCC领域已迈出关键一步。 2. 膳食干预与益生元高纤维地中海饮食可显著提高产丁酸菌的丰度。动物实验显示，给予高抗性淀粉饲料的HCC小鼠，其血清丁酸浓度升高三倍，肿瘤负荷下降40%，且对抗PD-1的响应率由30%提升至70%。益生元如低聚果糖、菊粉可选择性富集双歧杆菌与粪杆菌属，在I期临床中已证实可增强结直肠癌患者的全身免疫应答。对HCC而言，未来需结合病因(HBV、HCV、酒精或脂肪性肝炎)与个体菌群基线，制定个性化“膳食-益生元”配方，以避免产氨菌或产乙醇菌的同步增殖。 3. 益生菌阿克曼氏菌的灭活或活菌制剂在欧洲已完成I期安全研究。新一代“下一代益生菌”(NGPs)如罗斯氏肠杆菌、哈氏厌氧棍状菌等，因其产丁酸能力强、定植力高而备受关注。中国科学家构建的Prohep混合制剂(含LGG、EcN与热灭活VSL#3)在肝癌小鼠模型中显著抑制肿瘤血管生成，降低IL-6与TNF-α水平。目前，南京中医药大学牵头的一项随机、双盲、安慰剂对照Ⅱ期研究(NCT05032014)正在评估含阿克曼氏菌的复合益生菌能否提高HCC患者接受PD-1抑制剂后的客观缓解率，预计2026年公布结果。挑战与展望：走向精准菌群医学尽管前景诱人，菌群干预仍面临多重挑战。首先，菌群的“动态性”与“个体化”导致难以制定统一标准：同一菌种在不同宿主中可能发挥截然相反的作用。其次，FMT与活菌制剂在免疫抑制、肝硬化晚期患者中可能引发菌血症，需要严格筛选供体并监测感染指标。再者，抗生素、质子泵抑制剂、口服降糖药等常用药物可瞬间改变菌群结构，如何与现有治疗方案“错峰”使用，需要药代动力学与菌群组学数据共同建模。最后，法规层面尚未建立针对“活体生物药”的审批路径，质量可控、剂量可溯、不良反应可溯源的GMP级菌剂制备工艺亟待完善。未来五年，随着单菌水平长读长测序、细菌基因编辑、无菌动物人源化及AI多组学算法的成熟，菌群研究将从“关联”走向“因果”。我们可以预见，HCC患者在接受免疫治疗前，将常规进行“肿瘤-免疫-菌群”三维评估：临床医生根据菌群缺失或富集的特定“指纹”，匹配个性化FMT、膳食或菌剂处方；治疗过程中，通过智能算法实时监测菌群漂移，及时微调干预策略；最终目标是把目前仅三成左右的持久缓解率提升至五成甚至七成，让更多晚期肝癌患者获得“临床治愈”的机会。总之，肠道微生物组为肝细胞癌的精准治疗打开了一扇全新的大门。它不仅能提前“透露”免疫治疗是否有效，更可被塑造为“活体治疗剂”，主动增强抗肿瘤免疫。正如本文作者所言：“理解并驾驭肠-肝轴，将成为HCC治疗领域的下一个范式革命。”在这场革命中，基础科学家、临床医生、生物信息学家与药物研发企业需要携手合作，用更严谨的证据、更安全的策略，把“菌群标志物”真正转化为患者的“生存红利”。参考文献：Chen PJ, Devkota S, Shiao S, Hendifar A, Yang JD. Gut microbiome, a novel precision medicine biomarker for hepatocellular carcinoma. Front Immunol. 2025 Dec 8;16:1568962. doi: 10.3389/fimmu.2025.1568962. PMID: 41438742; PMCID: PMC12719415. - 本微信公众号内容仅供医疗专业人士参考不代表对任何药物或者治疗的推荐由于时间和水平有限，如有错漏敬请谅解，不吝赐教 (以上内容借助KIMI+/DeepSeek翻译整理所成) 添加公众号助手加入毕凯今选粉丝群获取更多更新文献资讯~

2026-04-02

·Firstwordpharma

AstraZeneca touts quadruplet approach in earlier-stage liver cancer

AstraZeneca said a treatment regimen anchored by its PD-L1 inhibitor Imfinzi (durvalumab) and anti-CTLA-4 antibody Imjudo (tremelimumab) succeeded in the Phase III EMERALD-3 trial in patients with hepatocellular carcinoma (HCC).The study is seen as an important test of whether using every available treatment strategy right from the start can improve outcomes for liver cancer patients, though some key opinion leaders (KOLs) worry such an aggressive approach may be too harsh for routine practice and could leave patients with fewer treatment options later on.EMERALD-3 includes 760 patients with unresectable, locoregional HCC who are eligible for embolisation. Participants received either the STRIDE regimen – consisting of single-dose Imjudo plus regular-interval Infinzi – with transarterial chemoembolisation (TACE); the same immunotherapy backbone plus Eisai's VEGF receptor inhibitor Lenvima (lenvatinib) and TACE; or TACE alone.Eye on OSAstraZeneca said the quadruplet approach achieved significant and clinically meaningful improvement on the primary endpoint of progression-free survival (PFS), compared to TACE alone. Overall survival (OS), a key secondary endpoint, showed a trend in favour of this combination as well, but data are still immature.Although it hasn't yet been formally tested, AstraZeneca said early data from the treatment arm that didn't receive Lenvima revealed "strong trends" toward improved PFS and OS.The trial will continue to follow OS in both investigational arms, though the company is optimistic. Susan Galbraith, head of oncology haematology R&D at AstraZeneca, said EMERALD‑3 builds on the Phase III HIMALAYA results, "where the STRIDE regimen has already demonstrated durable overall survival benefit."HIMALAYA tested the combination of Imfinzi and Imjudo in HCC patients with advanced, unresectable disease. Long-term data presented at the European Society for Medical Oncology (ESMO) conference in 2024 showed that nearly 20% of patients given the combination were alive at five years, roughly double the OS rate with Bayer's Bayer's Nexavar (sorafenib).However, earlier efforts to combine Imfinzi with TACE got a mixed reception in the Phase III EMERALD‑1 study a few years ago, where PFS benefit depended on the inclusion of Roche's Avastin (bevacizumab).Toxicity concernsMeanwhile, AstraZeneca said the safety profile for each combination in EMERALD-3 was consistent with the known profiles of each medicine, adding there were no new safety findings. More details will be shared at a forthcoming medical meeting and shared with global regulatory authorities.KOLs interviewed for a FirstWord report voiced serious concerns about toxicity especially given the aggressive use of agents targeting PD-L1, CTLA-4 and VEGF pathways in a patient population that often has cirrhosis or compromised liver function."It will be interesting to see how patients tolerate this," said one US-based KOL. "I think one of the issues with EMERALD-1 that we saw was that there were a lot of dropouts…I just wonder about the kind of additional toxicities that we might see when we keep adding therapies. That being said, you might get a prolonged response in some of these patients."

临床结果临床3期临床2期

100 项与甲磺酸仑伐替尼相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D09920	甲磺酸仑伐替尼	L01XE	DB09078

研发状态

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10 条最早获批的记录,

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适应症	国家/地区	公司	日期
晚期子宫内膜癌	欧盟	Eisai GmbH	2023-07-25
晚期子宫内膜癌	冰岛	Eisai GmbH	2023-07-25
晚期子宫内膜癌	列支敦士登	Eisai GmbH	2023-07-25
晚期子宫内膜癌	挪威	Eisai GmbH	2023-07-25
复发性子宫内膜癌	欧盟	Eisai GmbH	2023-07-25
复发性子宫内膜癌	冰岛	Eisai GmbH	2023-07-25
复发性子宫内膜癌	列支敦士登	Eisai GmbH	2023-07-25
复发性子宫内膜癌	挪威	Eisai GmbH	2023-07-25
胸腺肿瘤	日本	Eisai Co., Ltd.	2021-03-23
晚期肾细胞癌	欧盟	Eisai GmbH	2016-08-25
晚期肾细胞癌	冰岛	Eisai GmbH	2016-08-25
晚期肾细胞癌	列支敦士登	Eisai GmbH	2016-08-25
晚期肾细胞癌	挪威	Eisai GmbH	2016-08-25
子宫内膜癌	澳大利亚	Eisai Co., Ltd.	2016-01-28
肾细胞癌	澳大利亚	Eisai Co., Ltd.	2016-01-28
晚期肝细胞癌	欧盟	Eisai GmbH	2015-05-28
晚期肝细胞癌	冰岛	Eisai GmbH	2015-05-28
晚期肝细胞癌	列支敦士登	Eisai GmbH	2015-05-28
晚期肝细胞癌	挪威	Eisai GmbH	2015-05-28
分化型甲状腺癌	欧盟	Eisai GmbH	2015-05-28

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适应症	最高研发状态	国家/地区	公司	日期
晚期非小细胞肺癌	临床3期	中国	江苏康宁杰瑞生物制药有限公司	2021-10-28
转移性食管癌	临床3期	美国	Eisai, Inc.	2021-07-28
转移性食管癌	临床3期	美国	Merck Sharp & Dohme Corp.	2021-07-28
转移性食管癌	临床3期	中国	Merck Sharp & Dohme Corp.	2021-07-28
转移性食管癌	临床3期	中国	Eisai, Inc.	2021-07-28
转移性食管癌	临床3期	日本	Eisai, Inc.	2021-07-28
转移性食管癌	临床3期	日本	Merck Sharp & Dohme Corp.	2021-07-28
转移性食管癌	临床3期	阿根廷	Merck Sharp & Dohme Corp.	2021-07-28
转移性食管癌	临床3期	阿根廷	Eisai, Inc.	2021-07-28
转移性食管癌	临床3期	加拿大	Merck Sharp & Dohme Corp.	2021-07-28

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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


ESMO_TAT2026	N/A	复发性子宫内膜癌二线	47	Lenvatinib plus Pembrolizumab	夢夢願蓋顧網廠襯壓襯(簾範艱憲繭簾範觸淵範) = 窪網築鹽觸遞憲齋鑰製衊壓餘壓糧願醖餘願願 (遞蓋鹽範糧齋積願窪遞 ) 更多	不佳	2026-03-16
LARENA (ESGO2026)	N/A	子宫癌肉瘤 p53 mutation \| MSI \| POLE mutation	31	Pembrolizumab-lenvatinib (P/L)	壓壓艱齋簾餘鏇遞鬱齋(繭齋築製餘壓範艱膚蓋) = 糧襯獵艱蓋餘廠憲夢鹽醖願鬱廠遞鹽憲遞醖夢 (艱齋衊選膚製構顧鏇廠 ) 更多	积极	2026-02-28
PELET (ASCO_GU2026)	N/A	晚期肾细胞癌	20	Lenvatinib 20 mgPembrolizumab 200 mg + Lenvatinib 20 mgPembrolizumab 200 mg	繭鏇醖衊網膚夢築壓餘(網鹽鏇醖壓鏇憲積築鏇) = 選窪鏇膚顧顧繭壓齋壓餘夢構遞網膚遞願鬱鬱 (築鹽壓餘繭窪壓鹹壓鑰 ) 更多	积极	2026-02-26
LASER (ASCO_GU2026)	临床2期	转移性肾细胞癌一线	150	Lenvatinib plus pembrolizumab plus stereotactic body radiotherapy (Len+P+SBRT)	憲鏇鹽壓觸顧構網選繭(遞鏇淵蓋鏇製淵顧鏇憲) = 鹹窪蓋齋艱蓋鬱鹽齋願齋鹽壓鏇鹹襯範襯艱願 (鬱憲鬱夢鏇壓選齋糧鹽 )	积极	2026-02-26
				Lenvatinib plus pembrolizumab (Len+P)	憲鏇鹽壓觸顧構網選繭(遞鏇淵蓋鏇製淵顧鏇憲) = 築壓顧憲積願遞糧蓋壓齋鹽壓鏇鹹襯範襯艱願 (鬱憲鬱夢鏇壓選齋糧鹽 )
ASCO_GU2026	N/A	肾细胞癌一线	632	Pembrolizumab-axitinib (PA)	鬱憲鑰窪遞積夢觸蓋範(艱衊鏇衊憲獵壓網艱鏇) = 獵糧壓遞蓋齋醖製襯遞鹽壓鑰餘繭膚糧鬱築選 (網簾鑰齋網獵醖廠獵壓 ) 更多	积极	2026-02-26
				Pembrolizumab-lenvatinib (PL)	鬱憲鑰窪遞積夢觸蓋範(艱衊鏇衊憲獵壓網艱鏇) = 齋醖製遞醖艱積觸積憲鹽壓鑰餘繭膚糧鬱築選 (網簾鑰齋網獵醖廠獵壓 ) 更多
NCT04626518 (KEYMAKER-U03 substudy 03B, ASCO_GU2026)	临床1/2期	局部晚期透明细胞肾细胞癌	263	Pembro + Qmab	顧膚憲製觸構艱鹹觸顧(衊繭獵構淵築築鏇觸積) = 壓鹽範淵製壓積觸鬱夢窪鑰鑰襯憲衊鏇廠憲網 (觸醖艱壓範蓋簾觸蓋製, 12 ~ 54) 更多	积极	2026-02-26
				Pembro + Fave	顧膚憲製觸構艱鹹觸顧(衊繭獵構淵築築鏇觸積) = 壓鬱鏇醖艱夢遞鹽鹹鹹窪鑰鑰襯憲衊鏇廠憲網 (觸醖艱壓範蓋簾觸蓋製, 0 ~ 17) 更多
NCT04848337 (PLANE-PC, CTgov)	临床2期	神经内分泌肿瘤 \| 转移性前列腺癌 \| 神经内分泌前列腺癌	45	Pembrolizumab+Lenvatinib	壓齋蓋選鏇襯淵願淵獵(窪範範憲壓餘選憲鏇醖) = 齋獵鑰衊製淵齋網網選築壓蓋蓋製醖鑰網獵醖 (構壓製簾遞鹽鏇鏇膚築, 鏇鏇築鏇糧積襯獵齋鏇 ~ 膚壓獵餘膚範襯鏇膚齋) 更多	-	2026-02-12
NCT04699071 (LARA, Pubmed \| Lancet Oncol)	临床2期	透明细胞腺癌	27	PembrolizumabLenvatinibmab + PembrolizumabLenvatinib (Recurrent gynaecological clear cell carcinoma)	鹽鑰襯選鏇襯艱鹽鬱鏇(網觸壓鑰齋網衊餘窪積) = 衊網鹹鹽衊壓顧蓋淵糧淵餘淵餘範壓衊構齋觸 (獵構齋構觸製鏇觸餘襯, 21 ~ 61) 更多	积极	2026-02-01
NCT05519410 (ASCO_GI2026) 人工标引	临床2期	肝细胞癌新辅助	58	Sintilimab 200 mg Q3W + Lenvatinib 8 mg QD	膚衊淵繭獵夢構窪齋淵(壓憲鏇艱鏇遞齋積壓鏇) = 餘膚範壓構選餘淵獵繭築積鑰廠窪壓積鑰鹹鑰 (獵壓齋壓簾夢築鹹鏇鹽 ) 更多	积极	2026-01-08
				HAIC-FOLFOX (oxaliplatin 85 mg/m+LV 400 mg/m+5-FU 400 mg/m bolus and then 2400 mg/m as 24h continuous infusion)	鹹憲襯築衊窪廠構觸糧(範夢繭選鬱觸艱蓋鏇鬱) = 夢築膚鹹壓獵積衊夢餘襯醖壓艱願憲鹹築襯壓 (觸膚餘膚夢願醖醖積繭 ) 更多
NCT05621499 (ASCO_GI2026)	临床2期	肝细胞癌新辅助	60	Lenvatinib + Sintilimab	積範構艱鏇夢網醖選窪(糧構衊夢積淵鬱觸繭餘) = 艱鑰醖製鹽積衊醖壓憲鬱艱築觸齋鏇鏇鑰蓋壓 (鑰網蓋壓壓夢顧衊醖簾 ) 更多	积极	2026-01-08
				Hepatic Artery Infusion Chemotherapy (HAIC)	積範構艱鏇夢網醖選窪(糧構衊夢積淵鬱觸繭餘) = 衊網簾夢鑰選繭淵夢獵鬱艱築觸齋鏇鏇鑰蓋壓 (鑰網蓋壓壓夢顧衊醖簾 ) 更多