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更新于：2026-06-30

Trastuzumab

曲妥珠单抗

更新于：2026-06-30

概要

基本信息

药物类型

单克隆抗体

别名

Anti-HER2/neu-MAb、Nanotrastuzumab、trastuzumab

+ [18]

靶点

HER2

作用方式

拮抗剂

作用机制

HER2拮抗剂(受体蛋白酪氨酸激酶 erbB-2拮抗剂)、ADCC(抗体依赖的细胞毒作用)

治疗领域

肿瘤消化系统疾病口颌疾病+ [7]

在研适应症

HER2阳性结直肠癌HER2阳性唾液腺癌HER2阳性胃癌+ [40]

非在研适应症

腺癌晚期乳腺癌进展期胃腺癌+ [37]

原研机构

Genentech, Inc.

在研机构

上海罗氏制药有限公司

F. Hoffmann-La Roche Ltd.Roche Registration GmbH

+ [8]

非在研机构

Novartis Pharmaceuticals Corp.

Sanofi

Eisai, Inc.

+ [10]

权益机构-

最高研发阶段批准上市

首次获批日期

美国 (1998-09-25),

转移性乳腺癌

最高研发阶段(中国)批准上市

特殊审评加速批准 (美国)、孤儿药 (美国)、孤儿药 (日本)、优先审评 (美国)

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结构/序列

Sequence Code 18481L

来源: *****

Sequence Code 44772H

来源: *****

关联

1,246

项与曲妥珠单抗相关的临床试验

NCT07578116

/ Not yet recruiting临床3期IIT

Randomized Phase III Trial of Multimodality Therapy Versus Standard of Care Systemic Therapy in HER2 Positive (HER2+) De Novo (AJCC Stage IV) Oligometastatic Breast Cancer With Response to Initial Chemotherapy

This phase III trial evaluates the effect of adding locoregional therapy (surgery and radiation) and metastasis-directed stereotactic body radiation therapy (SBRT) to standard systemic therapy following standard HER2-targeted systemic therapy, compared to standard systemic therapy alone, in treating patients with HER2-positive stage IV breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or to a limited number of sites (oligometastatic). The usual approach for patients with (oligo)metastatic HER2-positive breast cancer is systemic drug treatment, which means medicines that travel through the whole body to treat both the breast and any areas where the cancer has spread. There are a number of approved HER2-targeted systemic therapy regimens available to patients. These typically include immunotherapy and/or chemotherapy. Immunotherapy drugs may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs 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. Unlike systemic therapy, locoregional therapies like surgery and radiation are focused treatments at the site of disease, delivered with the intent of sparing healthy tissues. Breast surgeries such as breast conserving therapy or total mastectomy are procedures in which the cancerous breast tissue (and healthy breast tissue in the case of total mastectomy) are surgically removed from the body. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Adding locoregional therapy, as well as metastasis-directed SBRT, to standard systemic therapy may help patients with (oligo)metastatic, HER2-positive stage IV breast cancer live longer overall or before their cancer progresses, and may help more patients achieve no evidence of disease, when compared to standard systemic therapy alone.

开始日期2027-03-09

申办/合作机构

SWOG

[+1]

CTIS2025-522431-34-00

/ Not yet recruiting临床2期

TAILOR-PANC: Molecularly Tailored Therapy versus Standard Care in Advanced Pancreatic Cancer (DPCG-02)

开始日期2026-10-01

申办/合作机构

Region Hovedstadens Apotek

NCT07136428

/ Not yet recruiting临床1/2期IIT

A Single Arm, Open-label Phase Ib/II Study of Asciminib in HER2+ Breast Cancer Brain Metastases (ASCENdANT)

The purpose of this study is to evaluate the intracranial response rate of a combination of asciminib/trastuzumab for the treatment of patients with metastatic HER2+ breast cancer with brain metastases.

开始日期2026-07-01

申办/合作机构

Duke University

[+1]

100 项与曲妥珠单抗相关的临床结果

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100 项与曲妥珠单抗相关的转化医学

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100 项与曲妥珠单抗相关的专利（医药）

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11,230

项与曲妥珠单抗相关的文献（医药）

2026-12-31·Human Vaccines & Immunotherapeutics

Cost-effectiveness of pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma

Article

作者: Yu, Kexin ; Xu, Qiaoping

To investigate the cost-effectiveness of pembrolizumab in combination with trastuzumab and chemotherapy as a first-line treatment for HER2-positive gastric or gastro-esophageal junction adenocarcinoma from the perspective of the U.S. and Chinese healthcare systems. In this economic evaluation, a Markov model is constructed from the perspective of the U.S. and Chinese healthcare systems. The survival data were derived from the clinical trial (KEYNOTE-811), while cost data generated during treatment were sourced from pricing, databases, and expert consultations in local hospitals. Total costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated in US dollars. Its robustness is evaluated by deterministic and probabilistic sensitivity analysis. Basic case analysis showed that pembrolizumab in combination with trastuzumab and chemotherapy, as a new treatment strategy, had higher cost-effectiveness compared with trastuzumab plus chemotherapy treatment, with willingness-to-pay (WTP) thresholds set at $150,000 per QALY for the United States population and $40,334.05 per QALY for the China population The ICER was $88,507.57 per QALY in the United States and $22,461.22 per QALY in China, both below the respective thresholds. Sensitivity analysis demonstrated that the results were robust. From the perspective of the U.S. and Chinese medical and health services, pembrolizumab in combination with trastuzumab and chemotherapy is more cost-effective than chemotherapy in the treatment of HER2-positive gastric or gastro-esophageal junction adenocarcinoma patients. Within the context of China's health technology assessment and National Reimbursement Drug List negotiation framework, the ICER below the three-times-GDP threshold suggests preliminary economic feasibility at current price levels, indicating that the regimen may warrant consideration for reimbursement decisions, subject to further budget impact analysis and price negotiation. The evidence-based pricing strategies provided in this study may be helpful for decision makers and clinicians to make the best decisions in general clinical practice. More evidence on budgetary impact and patient affordability is needed.

2026-12-31·mAbs

A novel insulin-like growth factor II-based masking domain for conditional activation of therapeutic antibodies

Article

作者: Shi, Lihua ; Cho, Minseon ; Nishida, Motohiko ; Chiu, Mark L. ; Zhang, Di

Systemic target engagement constrains the therapeutic index of many antibody drugs, particularly in inflammatory disease and immuno-oncology. Protease-cleavable masking can localize activity to disease sites, but existing approaches often tradeoff masking strength, reversibility, and developability. Here, we evaluated the insulin-like growth factor II (IGF-II) as a compact, structurally defined steric masking domain for protease-dependent conditional activation of therapeutic antibodies. IGF-II masking domains, including a receptor-silent variant (IGF-II-s), were engineered as N-terminal fusions to therapeutic antibodies via protease-cleavable linkers and characterized using antigen-binding and cell-based functional assays. IGF-II masking attenuated anti-TNFα binding and neutralization potency in a protease-dependent manner and activity was largely restored following cleavage. In vivo, an MMP2/9-cleavable masked anti-TNFα antibody retained efficacy comparable to adalimumab and infliximab in a collagen antibody-induced arthritis model, yet, unlike the reference antibodies, did not measurably reduce survival in a Listeria monocytogenes infection challenge model at the dose tested. IGF-II-s showed no detectable IGF receptor binding and provided stronger masking than native IGF-II. This generalized approach was demonstrated across multiple antibodies, enabling efficient protease-dependent conditional activation of trastuzumab (anti-HER2), an anti-IL-1β antibody, and bevacizumab (anti-VEGF). Together, these results established an engineered IGF-II-based masking domain as a versatile, IGF-II receptor-silent platform enabling protease-dependent conditional activation of therapeutic antibodies, with potential to improve safety and expand therapeutic windows.

2026-10-01·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Systematic development and optimization of a cIEF method for the charge variants analysis of moderately basic to basic monoclonal antibodies using the Analytical Quality by Design strategy

Article

作者: Orlandini, Serena ; Massolini, Gabriella ; Furlanetto, Sandra ; Pasquini, Benedetta ; Luciani, Francesca ; Floris, Lucrezia ; Gotti, Roberto

This study proposes a Capillary IsoElectric Focusing Analytical Procedure Platform for the charge heterogeneity characterization of monoclonal antibodies. The Analytical Quality by Design approach was implemented to define a robust Method Operable Design Region using Infliximab as the primary model compound. The Analytical Target Profile consisted in a robust Analytical Procedure Platform able to measure the monoclonal antibody isoforms pI values with a bias lower than 4%. Risk Management tools were used to evaluate and control the risk of Analytical Target Profile failure. Risk Analysis identified several potential Critical Procedure Parameters, including urea and methyl cellulose concentrations, cathodic/anodic stabilizer levels, carrier ampholytes composition. The carrier ampholytes composition was optimized utilizing a mixture design. A Scheffé mixture model allowed the selection of experiments, and the Partial Least Squares regression provided high predictive power models for the three defined responses, i.e. the calibration biases at the bracketing markers of Infliximab (pI 9.5 and pI 7.0) and the overall fit of the pI vs. migration time relationship. Within the Method Operable Design Region, the optimized conditions were achieved using as the specific carrier ampholyte a blend constituted of 1.5% at pH 3-10, 1.5% at pH 5-8, and 2.0% at pH 8-10.5. The validation results demonstrated the robustness of the Analytical Procedure Platform, with a bias in pI measurement lower than 0.3% for the markers bracketing the Infliximab isoforms. In addition, the method was validated for linearity, trueness and precision as degree of repeatability in the quantification of the charge variants of Infliximab. Under the same optimized experimental conditions, the method was applied to successfully profile Bevacizumab, Daratumumab, Trastuzumab and Durvalumab. By including molecules exhibiting a broader range of physicochemical properties compared to the Infliximab model, the study confirms the versatility of the proposed Capillary IsoElectric Focusing method for moderately basic to basic antibodies. This work provides a refined, regulatory-compliant conventional electrokinetic methodology for biopharmaceutical quality control.

3,854

项与曲妥珠单抗相关的新闻（医药）

2026-06-30

·小药说药

抗体偶联药物的肝相关毒性

-01- 引言 ADC被描述为“生物导弹”，由单克隆抗体、细胞毒性药物（载荷）和化学连接子三部分组成。自吉妥珠单抗奥唑米星（GO）获得FDA批准以来，ADC领域发展迅速。随着ADC在多种肿瘤中的临床应用不断扩大，治疗相关毒性——特别是肝毒性——引起了越来越多的关注。 ADC相关副作用影响包括肝脏在内的多个器官，并已导致FDA黑框警告。肝毒性在这些并发症中占显著比例，可导致致命后果，GO曾因严重肝毒性而被撤出市场。这一早期经验表明，肝损伤可能成为ADC安全使用和进一步开发的主要障碍。最近的一项荟萃分析发现，肝功能异常占所有级别不良事件的30%以上，占≥3级事件的18.8%，常需要减量或停止治疗。因此，ADC使用的增加突显了更好理解ADC相关肝毒性的机制、临床表现和管理策略的必要性。 -02- 一、ADC相关肝毒性的可能机制尽管ADC能比传统抗癌治疗更精确地靶向目标肿瘤部位，研究表明只有不到10%的给药ADC积累在目标肿瘤部位，而大部分仍留在循环中，可被正常细胞内化，可能导致毒性。由于肝脏的高灌注和包括FcγRIIb在内的内吞受体的丰富表达，肝窦内皮细胞（LSECs）特别容易受到ADC诱导的损伤。肝细胞和库普弗细胞均参与ADC在肝脏中的分布。肝细胞可通过被动扩散或转运体介导的摄取内化游离或去结合的细胞毒性载荷，而库普弗细胞和肝窦内皮细胞通过Fcγ受体和凝集素受体（如甘露糖受体）清除循环中的ADC和免疫复合物，这些过程在临床前和临床研究中与肝脏细胞因子反应改变和肝损伤相关。这些细胞事件为临床表现为血清ALT/AST升高、胆汁淤积、肝窦阻塞综合征（SOS），以及严重情况下的肝衰竭提供了机制基础。然而，ADC相关肝毒性的确切机制仍不完全清楚。 1 靶向毒性靶向毒性发生在ADC与肿瘤细胞和正常肝细胞中均存在的靶抗原结合时，导致肝毒性。研究证明GO通过CD33受体与正常细胞结合，导致肝窦毒性。然而，这并不能解释inotuzumab ozogamicin（InO）的肝毒性，其靶标CD22在正常肝细胞中不存在。Trastuzumab emtansine（T-DM1），一种靶向HER2的ADC，与显著肝毒性相关，而其他靶向HER2的ADC则显示出轻度毒性。这种差异突显了靶向机制的复杂性。总之，靶向毒性仅占ADC相关肝毒性的一小部分，因为靶抗原在肿瘤细胞中的表达通常高于正常组织。 2 脱靶毒性脱靶毒性指与靶抗原无关的不良反应，被认为是ADC毒性的主要机制。多种机制导致这些脱靶效应，包括：连接子不稳定性和偶联物解离：连接子的不稳定性和在非靶组织中过早释放载荷显著影响ADC的疗效和安全性。一项荟萃分析表明，ADC的毒性类型通常与载荷类型相关，以卡奇霉素为基础的ADC（如GO和InO）与肝窦阻塞综合征（SOS）和肝毒性的关联最强。 ADC中的连接子根据细胞毒性药物的释放机制分为可裂解型或不可裂解型。大多数已上市的ADC使用可裂解连接子，而不可裂解连接子需要蛋白水解降解，与降低的肝毒性相关但可能损害疗效，特别是对于低表达靶点。此外，连接子设计影响药物-抗体比（DAR），从而影响疗效、药代动力学和肝毒性。更高的DAR增加了ADC的疏水性和全身暴露，可增强其在肝脏等非靶组织中的积累，从而增加肝毒性风险。受体介导的内化：ADC的脱靶毒性可源于正常细胞通过特定受体的摄取，如Fcγ受体和甘露糖受体，这些受体与IgG抗体的Fc区域结合。虽然Fcγ受体通过抗体介导的功能增强ADC疗效，它们也导致毒性，包括肝窦中的SOS，特别是通过LSECs上的FcγRIIb。非靶细胞——特别是肝脏中——通过甘露糖受体介导的ADC摄取也可能导致肝毒性，正如GO所观察到的。甘露糖受体在多种细胞类型上表达，包括库普弗细胞和LSECs，并与ADC的Fc区域相互作用，促进其摄取并可能加剧肝脏毒性。肝细胞可通过细胞骨架相关蛋白5内化T-DM1，导致线粒体功能障碍和凋亡。非特异性内吞作用：内吞作用是细胞摄取营养物质和物质的关键过程，包括吞噬作用和胞饮作用。内吞作用的速率和机制因组织和细胞类型而异，免疫细胞如库普弗细胞和内皮细胞表现出特别高的速率。在一项对InO临床试验的回顾性分析中，发现InO相关的肝损伤可能与LSECs的非特异性内吞作用有关，尽管确切的实验证据仍缺乏。旁观者效应：旁观者效应是ADC脱靶毒性的关键机制。该现象发生在靶细胞内ADC降解后，游离载荷因其膜通透性、高度亲脂性，或作为靶细胞死亡的后果，被释放到肿瘤微环境中。释放的载荷随后可扩散到邻近的非靶细胞，导致非预期的细胞毒性。虽然旁观者效应增强了抗癌疗效，但也增加了肝毒性风险，对临床应用构成重大挑战。免疫原性相关肝毒性：免疫原性受多种因素影响，如药物结构、患者特征、剂量、给药频率和联合治疗，通常通过抗药物抗体（ADAs）进行评估。需要进一步研究ADC免疫原性及其与肝毒性的潜在关联，在开发和获批后进行持续评估对于确保安全性和疗效至关重要。 -03- 二、已获批ADC的肝毒性特征 Gemtuzumab ozogamicin 吉妥珠单抗奥唑米星（Gemtuzumab ozogamicin）是一种靶向CD33的单克隆抗体，通过可裂解连接子与DNA损伤剂卡奇霉素偶联，DAR为2-3。2000年获得FDA批准，GO于2010年因肝毒性和静脉闭塞性疾病（VOD）被撤出市场。然而，2012年的3期ALFA-0701试验表明，分次低剂量（3 mg/m²）改善了AML患者的结局且毒性可控，导致GO于2017年被FDA重新批准用于治疗成人和儿童CD33阳性AML。 GO临床试验中肝毒性相关不良事件发生频繁，通常表现为肝功能检测升高。大多数病例为1-2级严重程度。然而，VOD是一种可能危及生命的并发症，值得密切关注。ALFA-0701和AAML0531研究是成人及儿童AML联合治疗的关键3期研究，VOD的发生率分别为4.6%和3.5%。在ALFA-0701中，从GO给药到VOD发作的中位时间为9天（范围：2-298天）。快速体重增加通常是SOS最早期的临床表现。持续性血小板减少被视为VOD的早期指标，在上述两项临床试验中，GO组患者相比对照组显著更可能经历持续性血小板减少，表明存在未诊断的早期VOD的可能性。一项RCT和回顾性研究的荟萃分析发现，GO治疗组始终表现出一致更高的肝不良事件风险——包括VOD和SOS——高于非GO组，更高的GO剂量与增加的VOD/SOS发生率相关。病例报告表明，VOD通常发生在GO治疗的第一个周期内（常在1周内），其特征是胆红素和转氨酶水平升高、肝肿大、腹水和体重增加。 Brentuximab vedotin 本妥昔单抗维多汀（Brentuximab vedotin）是一种靶向CD30的ADC，由IgG1抗体、微管破坏剂MMAE和可裂解连接子组成，DAR为4，已获批用于治疗霍奇金淋巴瘤、间变性大细胞淋巴瘤和其他表达CD30的外周T细胞淋巴瘤。在临床试验中，最常报告的肝不良事件是转氨酶水平升高，不同研究中的发生率从10%到52%不等。上市后荟萃分析未能突出显著的肝毒性。一例接受BV单药治疗的患者报告了致命性肝毒性，表现为以血胆红素和ALP水平大幅升高为特征的急性肝损伤。肝活检结果提示胆汁淤积性药物诱导性肝损伤，临床医生将其归因于BV。 Trastuzumab emtansine 曲妥珠单抗恩他辛（Trastuzumab emtansine）是一种靶向HER2的单克隆抗体，通过不可裂解连接子与微管抑制剂DM1共价连接，DAR为3.5，已获批用于治疗转移性乳腺癌和作为早期高风险患者的辅助治疗。在T-DM1单药治疗的临床试验中报告了严重肝不良事件，包括三例致命病例（严重DILI和肝性脑病）。在关键临床试验中，转氨酶升高是接受T-DM1患者中最常报告的不良事件之一，也是减量或停止治疗的主要原因。在KATHERINE试验中，T-DM1组的转氨酶升高报告频率高于曲妥珠单抗组（ALT升高，23.1% vs. 5.7%；AST升高，28.4% vs. 5.6%）。结节性再生性增生（NRH）——一种可导致非肝硬化性门静脉高压的罕见肝脏疾病，与T-DM1相关——在KATHERINE和TH3RESA研究中分别有2/740和3/403例患者的肝活检中被识别出来。此外，TH3RESA试验报告了1例与T-DM1相关的肝性脑病死亡病例。 Inotuzumab ozogamicin 伊珠单抗奥唑米星（Inotuzumab ozogamicin）由靶向CD22的单克隆抗体、DNA损伤剂加利车霉素和可裂解连接子组成，DAR为2-3。InO和GO均使用相同的细胞毒性药物，并携带FDA关于肝毒性的黑框警告，包括致命性或危及生命VOD的风险。关键临床试验强调了InO治疗相关的显著肝毒性。在INO-VATE试验中，InO组治疗期间发生的肝毒性事件比标准治疗组更常见（51% vs. 34%）。此外，SOS发生在164例患者中的22例（13%），而标准治疗组仅1例（<1%）。从造血干细胞移植到SOS发作的中位时间为15天（IQR 10-17）。在ITCC-059研究中，评估InO单药治疗在儿科患者中的疗效和安全性，53例患者中有8例（15%）报告了SOS。值得注意的是，尚未有接受InO治疗的慢性HBV感染患者中出现HBV再激活的病例报道。一项包含10例在接受InO前进行过异基因造血细胞移植的患者的回顾性研究发现，3例患者出现VOD，导致一人死亡。上市后荟萃分析显示，接受InO的患者中VOD/SOS的合并发病率为8%，儿科患者（13%；95% CI，7%-21%）的发病率显著高于成人（6%；95% CI，3%-13%）。 Polatuzumab vedotin 波拉珠单抗维多汀（Polatuzumab vedotin）是一种靶向CD79b的单克隆抗体，通过可裂解连接子与MMAE偶联，DAR为3-4。PV已获批用于联合治疗弥漫性大B细胞淋巴瘤。在关键临床试验中，PV表现出一定的肝毒性，主要表现为ALT（20%-38%）和AST（13%-36%）水平升高。在GO29365研究中，接受PV联合苯达莫司汀和利妥昔单抗治疗的患者中，3级和4级转氨酶升高的报告率为1.9%。上市后回顾性研究未发现额外的显著肝毒性。 Enfortumab vedotin 恩诺珠单抗维多汀（Enfortumab vedotin）是一种靶向Nectin-4的ADC，由IgG1单克隆抗体通过可裂解连接子与MMAE偶联，DAR为4，已获批用于治疗局部晚期或转移性尿路上皮癌成人患者。在临床试验中，皮肤反应和周围神经病变作为EV的主要严重治疗相关不良事件比肝脏毒性更受关注。最常见的全级别肝脏相关不良事件是ALT和AST水平升高，5%-9%的患者经历≥3级升高。临床试验中未报告VOD或NRH病例。然而，在EV-301试验中，一名接受EV单药治疗的患者因肝功能异常死亡。上市后荟萃分析未发现额外的肝毒性，截至目前在FAERS中仅报告了114例（3.66%）肝胆系统疾病病例。 Trastuzumab deruxtecan 曲妥珠单抗德鲁替康（Trastuzumab deruxtecan）是一种靶向HER2的ADC，由单克隆抗体通过可裂解连接子与拓扑异构酶抑制剂德鲁替康连接，DAR为8，已根据多项关键临床试验的结果获批用于治疗成人实体瘤。在临床试验中，T-Dxd的肝毒性轻微，主要表现为转氨酶水平升高，所有级别发生率约为20%，通常不与剂量中断相关，但在DESTINY-CRC02试验中报告了一例与T-Dxd相关的致命性肝衰竭。上市后荟萃分析未能报告进一步的肝脏毒性，截至目前在FAERS数据库中仅有一小部分肝胆系统疾病病例的记录。 Sacituzumab govitecan 沙珠单抗戈维替康（Sacituzumab govitecan）是一种靶向TROP2的ADC，由单克隆抗体通过可水解连接子与SN-38偶联，平均DAR为7.6，已获批用于治疗成人三阴性乳腺癌，并已获得尿路上皮癌的加速批准。现有的临床试验数据表明，SG的肝毒性相对温和，肝脏相关不良事件主要由1-2级肝功能检测升高组成。对1,063例接受SG治疗的患者的汇总分析将ALP水平升高（28%）确定为最常见的不良反应之一。重要的是，没有因肝脏不良事件导致的剂量中断或药物相关死亡的报道。上市后分析进一步描述了肝脏安全性特征。最近一项使用FAERS数据库的药物警戒研究发现，除转氨酶升高外，与SG相关的肝胆毒性主要表现为急性胆囊炎和血胆红素水平升高，可能与药物通过胆囊排泄有关。 Belantamab mafodotin 贝兰他单抗马福维多汀（Belantamab mafodotin）包含靶向BCMA的单克隆抗体，通过抗蛋白酶连接子与微管抑制剂MMAF连接，DAR为4，适用于治疗多发性骨髓瘤成人患者。临床试验中肝脏不良事件轻微，多表现为肝功能检测异常，而血小板减少和角膜病变在临床应用中是更受关注的不良事件。在DREAMM-2研究中，接受BM治疗的患者中所有级别AST升高的患病率为20%，其中2%经历≥3级，所有级别ALP升高发生于8%的患者。临床试验中未报告因肝毒性导致的剂量中断或药物相关死亡。上市后荟萃分析未发现额外的肝脏毒性，截至目前在FAERS数据库中仅报告了少数肝胆系统疾病病例。 Loncastuximab tesirine 获批用于治疗DLBCL的隆卡珠单抗特西林（Loncastuximab tesirine）是一种靶向CD19的ADC，由抗CD19单克隆抗体通过可裂解连接子与细胞毒性烷化剂偶联，平均DAR为2.3。在临床试验中，LT相关的肝毒性主要表现为肝功能异常。与其他ADC不同，接受LT治疗的患者中更常观察到GGT升高。评估LT单药治疗复发或难治性DLBCL患者的2期LOTIS-2试验报告，所有级别GGT升高为41%，≥3级为17%。GGT升高也是导致治疗停止的最常见治疗期间出现的不良事件。然而，后续分析未在GGT升高的患者中发现任何级别的长期肝脏毒性。上市后数据未揭示额外的肝脏安全性问题。 Disitamab vedotin 维迪昔妥单抗维多汀（Disitamab vedotin）是一种靶向HER2的ADC，由单克隆抗体通过可裂解连接子与MMAE连接，DAR为4，已在中国获批用于治疗尿路上皮癌和胃癌。肝功能异常是临床试验中观察到的最常见肝不良事件之一，发生率为11.6%-43.2%，主要为1-2级。对414例接受维迪昔妥单抗维多汀治疗的患者进行的汇总安全性分析显示，转氨酶水平升高是最常见的不良事件，所有级别发生率为55.8%，主要为1-2级。转氨酶升高导致5.1%的患者延迟给药，2.3%的患者调整剂量。未报告肝毒性相关死亡。真实世界研究也显示出轻度肝毒性，主要表现为可逆且可控的转氨酶升高。 Tisotumab vedotin 替索珠单抗维多汀（Tisotumab vedotin）是一种靶向组织因子的ADC，由抗TF单克隆抗体通过可裂解连接子与MMAE偶联，DAR为4，于2024年4月获得FDA批准用于治疗复发或转移性宫颈癌成人患者。现有的临床试验表明，替索珠单抗维多汀相关的肝毒性为中度，主要表现为肝功能异常。大多数肝毒性相关不良事件为1-2级，未报告肝毒性相关死亡。上市后荟萃分析未发现额外的肝脏毒性，截至目前在FAERS中仅报告了9例肝脏检查异常病例和3例肝胆系统疾病病例。 Mirvetuximab soravtansine 米维妥昔单抗索拉维坦新（Mirvetuximab soravtansine）是一种靶向叶酸受体α的ADC，由单克隆抗体通过可裂解连接子与抗微管蛋白剂DM4偶联，平均DAR为3.3-5，适用于治疗FRα阳性、铂耐药的上皮性卵巢癌、输卵管癌或腹膜癌成人患者。与携带FDA黑框警告的显著眼毒性相比，现有临床试验数据表明MIRV的肝毒性相对轻微。肝脏不良事件主要表现为肝功能异常，发生率低于20%，大部分为1-2级严重程度。唯一导致减量或延迟的肝脏不良事件是FORWARD I研究中3例（1%）AST升高。未报告肝毒性相关死亡。对来自四项临床研究的682例MIRV治疗患者的整合安全性分析显示低肝毒性，16%和13%的患者分别经历ALT升高和AST升高（所有级别），<1%的病例达到≥3级严重程度。 -04- 结语 ADC治疗领域近年来发展迅速，目前已有17种ADC获批，众多候选药物处于临床试验阶段。尽管取得了显著进展，肝毒性仍然是限制ADC广泛应用的主要障碍。未来的研究应聚焦于识别ADC诱导肝毒性的患者特异性和药物特异性风险因素，包括遗传易感性、合并症以及载荷和连接子等药物特征。这些方面的进展将有助于减轻ADC相关不良效应、增强治疗安全性和疗效，并最终为更安全、更个性化的抗体药物偶联物疗法铺平道路。参考资料： Navigating hepatotoxicity of antibody-drug conjugates: from mechanistic insights to clinical and postmarketing evidence. Front Pharmacol. 2025 Dec 5:16:1694436.

2026-06-30

·PRNewswire

EirGenix Showcases Dual-Track Biosimilars and CDMO Strategy in U.S. Market Push at BIO 2026

SAN DIEGO, June 30, 2026 /PRNewswire/ -- At BIO 2026, EirGenix presented its comprehensive HER2-positive breast cancer biosimilar portfolio and highlighted its integrated one-stop contract development and manufacturing organization (CDMO) service platform. The company actively pursued U.S. market opportunities through business matchmaking and global partnership discussions. While antibody-drug conjugates, other oncology and immunology biologics, and biosimilars continue to drive growth, CDMOs are gaining strategic importance amid ongoing global supply chain restructuring. Continue Reading EirGenix showcases its complete HER2-positive breast cancer biosimilar product portfolio and one-stop integrated CDMO platform at BIO 2026. Image: GeneOnline In an industry shifting from single-product competition toward platform-based and combination-therapy strategies amid geopolitical uncertainty, EirGenix addresses the challenge of finding new growth engines in mature markets through its dual-track approach. By combining targeted biosimilar development with a flexible CDMO model, the company captures high-potential oncology opportunities while helping partners accelerate global commercialization. Breast Cancer Remains a Core Battlefield in Oncology Innovation According to the World Health Organization (WHO), approximately 2.3 million women were diagnosed with breast cancer in 2022, making it the second most commonly diagnosed cancer worldwide. The large patient population and steadily rising treatment demand continue to drive sustained pharmaceutical investment in the field. Market research from Grand View Research projects that the global breast cancer drug market will expand from USD 36.6 billion in 2024 to USD 69.7 billion by 2033, representing a compound annual growth rate (CAGR) of 7.1%. HER2-positive breast cancer accounts for approximately 15% to 20% of all breast cancer cases. Historically, this subtype was associated with aggressive tumor biology and poor prognosis. However, the introduction of trastuzumab validated HER2 as a therapeutic target and reshaped the treatment paradigm. Since then, innovation in HER2-positive therapy has accelerated. Dual-target regimens, subcutaneous formulations, and antibody-drug conjugate (ADC)-based approaches have reshaped the competitive landscape. Today, differentiation extends beyond efficacy, increasingly focusing on treatment convenience and patient experience. Biosimilars for HER2-Positive Breast Cancer Drive EirGenix's Next Growth Phase The global biopharmaceutical industry is entering a major patent cliff, as approximately $300 billion of biologics are expected to lose patent protection over the next decade. This transition is creating significant opportunities for biosimilar developers across major therapeutic areas, especially in oncology and immunology. This is unlocking a vast market potential for biosimilars. While 118 biologics are set to lose exclusivity by 2034, a striking 106 of them currently have no biosimilars in development. At the same time, global regulatory frameworks are becoming increasingly harmonized. Agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are aligning expectations for biosimilar approval pathways. Development requirements are increasingly focused on in vitro comparability and on pharmacokinetic bioequivalence data, reflecting a more streamlined regulatory approach. This shift is reducing reliance on large-scale Phase III clinical trials, ultimately shortening development timelines while lowering costs and clinical risk. Against this backdrop, EirGenix has strategically prioritized HER2-positive breast cancer within its biosimilar portfolio. The company's pipeline spans multiple modalities, including trastuzumab and pertuzumab, as well as subcutaneous combination formulations designed to improve treatment convenience and administration efficiency. In parallel, EirGenix is advancing development efforts in next-generation ADC biosimilars. Beyond single-agent development, EirGenix is also exploring combination therapy strategies to address mechanisms of resistance in oncology treatment. These include potential co-development approaches involving ADC biosimilars alongside immune checkpoint inhibitors such as atezolizumab, as well as other targeted therapies including daratumumab. As additional oncology biologics approach patent expiration, the company continues to evaluate and prioritize future targets across its development pipeline. This proactive portfolio strategy is designed to strengthen its positioning in the rapidly evolving immuno-oncology biosimilar landscape. Supply Chain Restructuring Elevates the Strategic Role of CDMO Partners Beyond biosimilars, CDMO services represent a second core pillar of EirGenix's business strategy. Global supply chain restructuring, the rapid rise of biotech startups, and increasing demand for biologics are reshaping outsourcing models across the pharmaceutical industry. In the United States, companies of all sizes are increasingly relying on external partners to support both development and manufacturing activities. This shift is driven by the need to reduce capital expenditure while improving R&D efficiency and operational flexibility. With demonstrated leadership in commercial-scale GMP biologics manufacturing, EirGenix provides integrated CDMO services across the full product lifecycle. Unlike development-focused CDMOs with limited scale and late-stage capabilities, EirGenix operates a fully integrated, commercially scaled platform spanning cell line engineering, process and analytical development, technology transfer, and GMP manufacturing. This delivers strong performance across the entire value chain from early-stage development through commercialization. Its service scope covers monoclonal antibodies, bispecific antibodies (BsAbs), and other complex biologics. By integrating these capabilities, EirGenix expands cross-border collaboration opportunities and reinforces its positioning in the global biologics outsourcing market. EirGenix Advances Dual-Track Growth in Biosimilars and CDMO Services at BIO Convention The United States remains the largest pharmaceutical market globally. At BIO 2026, EirGenix strengthened its international visibility by showcasing its R&D capabilities and engaging in active partnering discussions and industry networking. The company reiterated its commitment to expanding its global footprint, with a strategic focus on capturing opportunities from biosimilar patent expirations and increasing global demand for CDMO partnerships. EirGenix highlighted its long-term dual-track growth strategy: advancing high-value biosimilar assets while leveraging its commercial-scale development and manufacturing platform to support global clients across the entire product lifecycle. This integrated approach is designed to accelerate development timelines for partners while improving commercialization efficiency. Ultimately, it positions EirGenix as an integrated enabler within the rapidly growing global biologics ecosystem. Contact: Press GeneOnline [email protected] +886-225140360 SOURCE EirGenix 21% more press release views with Request a Demo

临床3期抗体药物偶联物

2026-06-30

·药闻康策

安徽牵头生物药集采近在眼前！

☝ 点击上方一键预约 ☝ 最新最热的医药健康新闻政策 ☝ ☝ 点击查看峰会活动议程 ☝ ☝ 近日，据业内流传，安徽省医保局已发函邀请各省参与针对单抗类药品的全国生物制剂联盟集中带量采购，函复截止时间为6月26日。此次流出的拟采购药品共有7个，分别是阿达木单抗、贝伐珠单抗、地舒单抗、利妥昔单抗、曲妥珠单抗、托珠单抗、英夫利西单抗。一、生物药集采的渐进式推进与现实困境综上所述，不同于化学药集采的快速扩围、雷厉风行，生物药集采的每一步都走得格外谨慎、节奏几度放缓，这场由安徽牵头的全国性生物药联采，为何推进如此艰难？主要原因可能有以下几点：一致性（相似性）评价：原研生物药和生物类似药之间往往有较大的变异性，不同厂商的产品之间变异性较大，其互相替代性往往存在较大争议；临床可替代性：生物药的替代需兼顾安全性与有效性，大规模强制替代可能带来临床风险。降价空间：生物类似药研发成本高，定价通常较高，“专利悬崖” 带来的价格跳水效应并不突出。复盘国内已落地的生物药集采项目，其整体降价幅度也普遍更为温和，例如：第六批国采中选平均降幅48%；广东双氯芬酸联盟第一轮人血白蛋白平均降幅33%，最高降幅42%；供应产能：生物药的生产工艺复杂，设备投入大，生产周期长，产能扩张存在物理上限和长期周期。因此，生物药集采面临更大的产能瓶颈，一旦中选企业对产能预估不足，极易引发全国性短缺，风险更高...... 二、国内生物药带量采购现状目前国内涉及生物药的省级带量采购数已经超过30个，且生物药则在大多数情况下与化药共享一套拟中选规则，或增设专属差异化条款。截至目前，除了第六批国采（胰岛素专项）外，省级维度只有江西牵头干扰素联盟和即将开展的安徽牵头单抗联盟是生物药专项带量采购，另有广东双氯芬酸联盟将血液制品单列制定规则，其他生物药仍与化药同组竞争。部分国家、省级带量采购目录构成：已被纳入集采的生物药：共33个生物药品被纳入集采，其中广东在将生物药引进带量采购方面一直走在前列，33个生物药中，大部分都是由广东牵头的双氯芬酸联盟首先引入带量采购领域，但受限于当时参与地区数，影响力并未扩大到全国大部分地区。随着2025年双氯芬酸联盟接续，参与地区数翻倍，采购目录内生物药也被更多地区纳入集采范畴。三、生物药带量采购规则解析结合历次生物药集采项目：2021年广东双氯芬酸联盟、2023年浙江第四批集采、2024年江苏第五轮集采、2025年云南昭通第二批带量联动、2022年安徽部分化药生物药集采、2023年安徽部分化药生物药集采等的分组规则、中选规则、分量规则，所得混合采购项目规则如下：四、安徽单抗类生物药集采品种竞争格局最后，梳理了安徽生物药集采拟采购的7个品种的竞争格局，供大家参考。以上表格更新时间截至20260623 竞争企业数最多的是贝伐珠单抗，已有13家企业上市，其次为阿达木单抗，已有9家企业上市，剩余5个品种竞争企业数较为接近。企业方面，涉及品种数最多的是国外企业罗氏，涉及贝伐珠单抗等4个品种，国内企业正大天晴同样涉及4个品种。五、总结安徽牵头单抗类生物制剂联盟或将于2026年下半年正式启动。这或将是生物药集采常态化的开端，未来集采范围有望逐步扩展。但生物药集采大概率不会复刻化药集采的激进路径，其会始终保持审慎的节奏。对于药企而言，也需要尽快适应这种温和但持续的降价趋势：靠生物类似药的 “首仿红利” 躺赢的时代即将结束，成本控制能力、产能规模优势、创新管线储备，都将成为未来竞争的核心支柱。（来源：易联招采网）药闻康策新媒体矩阵微信公众号点击下方一键关注【免责声明】 1.“药闻康策”部分文章信息来源于网络转载是出于传递更多信息之目的，并不意味着赞同其观点或证实其内容的真实性。如对内容有疑议，请及时与我司联系。2.“药闻康策”致力于提供合理、准确、完整的资讯信息，但不保证信息的合理性、准确性和完整性，且不对因信息的不合理、不准确或遗漏导致的任何损失或损害承担责任。3.“药闻康策”所有信息仅供参考，不做任何商业交易或医疗服务的根据，如自行使用“药闻康策”内容发生偏差，我司不承担任何责任，包括但不限于法律责任，赔偿责任。欢迎转发分享、点赞、点在看

100 项与曲妥珠单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03257	曲妥珠单抗	L01XC03	DB00072

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
HER2阳性结直肠癌	日本	Chugai Pharmaceutical Co., Ltd.	2022-03-28
HER2阳性唾液腺癌	日本	Chugai Pharmaceutical Co., Ltd.	2021-11-25
HER2阳性胃癌	日本	Chugai Pharmaceutical Co., Ltd.	2011-03-10
胃癌	美国	Genentech, Inc.	2010-10-20
乳腺癌	日本	Chugai Pharmaceutical Co., Ltd.	2001-04-04
早期乳腺癌	欧盟	Roche Registration GmbH	2000-08-28
早期乳腺癌	冰岛	Roche Registration GmbH	2000-08-28
早期乳腺癌	列支敦士登	Roche Registration GmbH	2000-08-28
早期乳腺癌	挪威	Roche Registration GmbH	2000-08-28
HER2阳性乳腺癌	欧盟	Roche Registration GmbH	2000-08-28
HER2阳性乳腺癌	冰岛	Roche Registration GmbH	2000-08-28
HER2阳性乳腺癌	列支敦士登	Roche Registration GmbH	2000-08-28
HER2阳性乳腺癌	挪威	Roche Registration GmbH	2000-08-28
HER2阳性胃食管结合部腺癌	欧盟	Roche Registration GmbH	2000-08-28
HER2阳性胃食管结合部腺癌	冰岛	Roche Registration GmbH	2000-08-28
HER2阳性胃食管结合部腺癌	列支敦士登	Roche Registration GmbH	2000-08-28
HER2阳性胃食管结合部腺癌	挪威	Roche Registration GmbH	2000-08-28
HR阳性乳腺癌	欧盟	Roche Registration GmbH	2000-08-28
HR阳性乳腺癌	冰岛	Roche Registration GmbH	2000-08-28
HR阳性乳腺癌	列支敦士登	Roche Registration GmbH	2000-08-28

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
膀胱癌	临床3期	英国	-	2023-03-07
结直肠癌	临床3期	英国	-	2023-03-07
胆囊肿瘤	临床3期	英国	-	2023-03-07
血液肿瘤	临床3期	英国	-	2023-03-07
肺癌	临床3期	英国	-	2023-03-07
卵巢癌	临床3期	英国	-	2023-03-07
胰腺癌	临床3期	英国	-	2023-03-07
前列腺癌	临床3期	英国	-	2023-03-07
唾液腺肿瘤	临床3期	英国	-	2023-03-07
皮肤肿瘤	临床3期	英国	-	2023-03-07

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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


NCT04858529 (neoCARHP, Pubmed \| J Clin Oncol)	临床3期	HER2阳性乳腺癌新辅助 HER2-positive	766	Taxane + Trastuzumab + Pertuzumab + Carboplatin	衊積廠糧夢鬱鏇鑰艱齋(廠鹹鏇選醖齋獵夢網齋) = 製製觸積範願製積簾範蓋製夢餘艱鬱襯鹽淵繭 (製鹽鑰積鹹鑰獵選網繭, 60.9 ~ 70.6) 更多	积极	2026-06-10
				Taxane + Trastuzumab + Pertuzumab	衊積廠糧夢鬱鏇鑰艱齋(廠鹹鏇選醖齋獵夢網齋) = 選鏇憲餘鏇蓋鹽製獵築蓋製夢餘艱鬱襯鹽淵繭 (製鹽鑰積鹹鑰獵選網繭, 59.1 ~ 69.0) 更多
NCT05749900 (KCSG-HB23-05, ASCO2026)	临床1/2期	HER2阳性胆道肿瘤一线 HER2-positive	40	Cisplatin 25mg/m²Trastuzumab 6mg/kg (after 8mg/kg load)Nivolumab 360mg/kg (after 8mg/kg load) + Cisplatin 25mg/m²Trastuzumab 6mg/kg (after 8mg/kg load)Nivolumab 360mg + Cisplatin 25mg/m²Trastuzumab 6mg/kg (after 8mg/kg load)Nivolumab 360mgm² + Cisplatin 25mg/m²Trastuzumab 6mg/kg (after 8mg/kg load)Nivolumab 360mg0mg/m² (dose level 0) or 800mg/m² (dose level -1)	窪鑰積蓋憲憲膚製網構(鏇觸廠積繭遞築簾遞窪) = 憲憲鏇夢簾積鬱鏇積構艱鏇選範鑰淵鹹淵醖壓 (糧選窪鹹膚鹹齋衊夢顧, 38.5 ~ 70.7) 更多	积极	2026-05-29
ASCO2026	N/A	HER2阳性胃癌 HER2-positive	229	Trastuzumab plus chemotherapy (HER2-positive gastric cancer)	齋鹽膚遞簾獵願繭鏇繭(衊構觸顧夢積鑰膚艱窪): HR = 0.74 (95.0% CI, 0.44 ~ 1.25), P-Value = 0.26 更多	不佳	2026-05-29
				Chemotherapy alone (HER2-positive gastric cancer)
ASCO2026	N/A	HER2阳性乳腺癌新辅助 HER2-positive	219	Biosimilar Pertuzumab with Trastuzumab	襯範鹽繭網繭膚積鏇襯(積選顧鑰範憲窪醖鏇廠) = No significant adverse events reported other than diarrhoea. None of them had treatment discontinuation due to cardiac toxicity. 繭鹹鬱鹽積鏇鹹觸簾壓 (壓網鏇鬱網製鏇範夢簾 )	积极	2026-05-29
				Phesgo (Pertuzumab/Trastuzumab/Hyaluronidase)
NCT04383275 (IRIS-A, ASCO2026)	临床2期	HER2阳性乳腺癌辅助 HER2-positive	187	Capecitabine and Trastuzumab	鹽網鏇鹹蓋廠積範蓋艱(鹹繭簾鏇築網膚構繭積) = 願餘簾齋膚憲遞構繭艱繭構糧蓋夢鹹醖獵膚襯 (簾夢構艱壓衊蓋範積選, 94.4 ~ 99.2) 更多	积极	2026-05-29
ASCO2026	N/A	HER2阳性乳腺癌辅助 HER2-positive	87	Trastuzumab+pertuzumab	齋鑰鹹積選網憲壓網淵(獵壓淵廠餘願餘鏇壓淵) = 獵鑰積鹹齋網壓蓋範憲鬱獵製繭夢齋製淵築願 (襯願衊憲網糧製餘廠範, 28.5) 更多	积极	2026-05-29
				Trastuzumab	積夢鹽積鹽壓鑰餘選廠(觸膚鹽製繭鬱築襯廠範) = 齋範鏇積膚醖鹽鑰蓋積網糧艱壓膚鹹鏇繭夢顧 (顧獵積獵鹹淵蓋憲齋淵 )
ASCO2026	N/A	HER2阳性乳腺癌 HER2+	208	trastuzumab (6 months)	積廠衊築鏇醖窪築窪糧(範餘壓廠糧願鑰繭鑰製) = 鏇繭廠糧顧膚製鏇襯廠選遞齋醖觸簾獵壓淵廠 (鑰鹹鏇鏇餘憲鑰廠網窪 ) 更多	积极	2026-05-29
				trastuzumab (12 months)	積廠衊築鏇醖窪築窪糧(範餘壓廠糧願鑰繭鑰製) = 選淵齋憲糧齋淵繭鹹遞選遞齋醖觸簾獵壓淵廠 (鑰鹹鏇鏇餘憲鑰廠網窪 ) 更多
ASCO2026	N/A	转移性乳腺癌 HR+/HER2+	957	Dual HER2 blockade + ET without induction	顧範膚糧製壓膚夢構窪(範窪艱蓋範願膚構襯遞) = 餘鏇夢製壓壓簾襯壓繭選積餘觸製鹹膚夢醖顧 (獵襯構遞顧鏇鹽鑰壓艱 ) 更多	积极	2026-05-29
				Dual HER2 blockade + ET with taxane induction	顧範膚糧製壓膚夢構窪(範窪艱蓋範願膚構襯遞) = 醖廠網夢鏇齋鬱膚選壓選積餘觸製鹹膚夢醖顧 (獵襯構遞顧鏇鹽鑰壓艱 ) 更多
ASCO2026	N/A	HER2阳性乳腺癌 HER2-positive	687	Trastuzumab-based regimens	蓋網鹹齋憲顧醖顧繭觸(製鹹夢壓範鹽鬱窪積鹽) = Event-free survival curves showed marked overlap among low-, moderate-, and high-risk groups. 鹽網觸鏇顧醖製醖鹹壓 (夢築製夢構簾壓壓鏇壓 )	不佳	2026-05-29
NCT06483386 (ASCO2026)	临床2期	HER2阳性乳腺癌新辅助 HER2-positive	47	Pyrotinib+SC trastuzumab+capecitabine (HER2-positive early breast cancer)	窪網衊憲構壓製鹽餘艱(淵糧範鏇簾選選鑰糧簾) = 觸網艱鹹製鹹製醖鏇積築齋顧齋獵願顧築淵糧 (餘壓鹽範齋襯製鑰獵選 ) 更多	积极	2026-05-29
				Pyrotinib+SC trastuzumab+capecitabine (ER negative, HER2 positive)	窪網衊憲構壓製鹽餘艱(淵糧範鏇簾選選鑰糧簾) = 糧膚鏇鹹鹹鏇醖夢顧齋築齋顧齋獵願顧築淵糧 (餘壓鹽範齋襯製鑰獵選 )