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trastuzumab (Vivitra)

✓ Approved

Ligand Pharmaceuticals · ERBB2 · 单克隆抗体

什么是 trastuzumab？

trastuzumab 是一种单克隆抗体，由Ligand Pharmaceuticals研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intravenous (IV)。

药物档案

商品名Vivitra
公司Ligand Pharmaceuticals
药物类别单克隆抗体, 抗体
分子靶点ERBB2
给药途径Injectable (Others), Intravenous (IV)
状态Approved
来源： ClinicalTrials.gov, Ligand Pharmaceuticals

作用机制

分子靶点

trastuzumab 作用于 1 个分子靶点：

ERBB2erb-b2 receptor tyrosine kinase 2 (NEU, CD340)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

trastuzumab 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Breast cancer✓ Approved

相关研究文献

PubMedAntibodies (Basel, Switzerland)2026-10-26

Complement in HER2-Positive Breast Cancer: A Conditionally Protective Mechanism Under Attack.

Petkova Dobromira D, Kuleva Ivaila I, Stoyanova Zhasmin Z, Ilcheva Boryana B et al.

The therapeutic efficacy of anti-HER2 monoclonal antibodies in breast cancer has traditionally been attributed to direct inhibition of signaling and antibody-dependent cellular cytotoxicity (ADCC). Recent evidence, however, has established complement activation through the classical pathway as a possible adjunct mechanism underlying the synergistic activity of the trastuzumab and pertuzumab combination. This synergy is mediated by complement-dependent cytotoxicity (CDC) and complement-dependent cellular phagocytosis (CDCP), and is lost upon C1q deletion in preclinical models. Tumor cells evade complement-mediated killing through overexpression of membrane-bound complement regulatory proteins (mCRPs), particularly CD55 and CD59, which correlate with shorter disease-free survival in patients treated with trastuzumab. C1q itself plays a dual, context-dependent role: it acts as a complement-independent tumor suppressor in HER2-positive breast cancer while promoting tumor progression in most other malignancies. Emerging therapeutic strategies, including biparatopic antibodies such as zanidatamab, complement-redirecting immunoconjugates, and mCRP-targeting approaches, aim to overcome complement resistance and enhance antitumor immunity. On this basis, we propose that HER2-positive breast cancer represents a conditionally complement-protective tumor, in which the balance between antibody-directed complement activation and mCRP-mediated evasion determines treatment outcome. This review evaluates the current evidence linking complement to anti-HER2 therapy and highlights future directions for successful treatment.

PMID 42930033
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PubMedMolecular cancer therapeutics2026-10-26

Preclinical modeling of trastuzumab deruxtecan in a mouse model of brain metastatic triple-negative breast cancer identifies two contributors to efficacy.

Khan Imran I, Kumar Dinesh D, Difilippantonio Simone S, Robinson Christina C et al.

Trastuzumab deruxtecan (T-DXd) has demonstrated clinical efficacy in advanced HER2-low to -ultralow breast cancer. We employed a mouse model of triple-negative breast cancer in the difficult-to-treat brain metastasis setting to determine T-DXd efficacy and investigate mechanism(s). T-DXd (10 and 3 mg/kg) was compared to an identical ADC except HER2-nonbinding (control) in a hematogenous model of HER2-ultralow brain-tropic triple-negative breast cancer, MDA-MB-231-BR7 (231-BR). The roles of HER2 and the neonatal Fc receptor (FcRn) were determined by CRISPR-Cas9 deletion and shRNA knockdown, respectively. 231-BR cells exhibited HER2 0+ staining, with occasional membrane expression. T-DXd at 10 mg/kg reduced 231-BR brain metastases by 49% (P=0.002), while a dose reduction showed a 30% (ns) metastasis reduction, each compared to the control-ADC. HER2-specific and -nonspecific ADC uptake into metastases was accompanied by a 23-47% tumor cell Ki-67 decline, and 5-fold increase in tumor apoptosis. A HER2 CRISPR-Cas9 knockout 231-BR formed multiple brain metastases but was insensitive to T-DXd in vivo. 231-BR tumor cells expressed FcRn, potentially enabling nonspecific ADC uptake. Analysis of human tumors showed TNBC tumors expressed FcRn mRNA. T-DXd failed to inhibit brain metastases in two 231-BR FcRn knockdown clones compared to a 231-BR clone transduced with a scrambled shRNA where T-DXd inhibited brain metastases (67% reduction, P=0.01). Despite ultralow HER2 expression, the HER2 binding capacity of T-DXd is a significant contributor to its efficacy. Breast cancers variably express FcRn, suggesting that nonspecific tumor cell uptake of T-DXd via FcRn is also a potential mechanism of T-DXd action.

PMID 42929047
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PubMedCurrent oncology (Toronto, Ont.)2026-10-26

A New Era of Treatment Sequencing in Platinum-Resistant Ovarian Cancer: Integrating Immunotherapy, Antibody-Drug Conjugates, and Targeted Therapies.

Mabuchi Seiji S, Kusakabe Ai A, Takimoto Yumi Y

Platinum-resistant ovarian cancer (PROC) has historically been treated with sequential non-platinum chemotherapy, with bevacizumab added when appropriate. The therapeutic landscape has expanded with positive randomized phase III data for pembrolizumab plus weekly paclitaxel with or without bevacizumab (KEYNOTE-B96), mirvetuximab soravtansine (MIRV) in FRα-high disease (MIRASOL), and relacorilant plus nab-paclitaxel (ROSELLA). Trastuzumab deruxtecan (T-DXd) has also shown substantial activity in previously treated HER2-expressing ovarian cancer, although its ovarian cohort was small, nonrandomized, and not restricted to PROC. These trials enrolled different populations and do not establish a cross-trial efficacy hierarchy. We therefore review the development of immunotherapy leading to KEYNOTE-B96, compare newer strategies with established PROC treatments, distinguish phase III evidence from regulatory approval and routine availability, and propose an evidence-informed framework for treatment selection and sequencing. The framework prioritizes current treatment opportunity while accounting for biomarker eligibility, prior treatment, residual toxicity, treatment and financial burden, patient priorities, and the feasibility of later-line therapy.

PMID 42930189
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PubMedJournal of biological engineering2026-10-26

A stealth-body Fc engineering platform enables complete effector silencing in antibody and ADC therapeutics.

Kim Suyeon S, Jo Migyeong M, Kyung Munsu M, Ko Woo Hyung WH et al.

The development of next-generation antibody therapeutics requires Fc scaffolds that suppress unwanted effector functions while preserving core developability attributes. Existing effector-attenuated Fc backbones, however, retain residual interactions with Fcγ receptors (FcγRs) and C1q, highlighting a persistent design limitation in achieving complete effector silencing without compromising glycosylation, FcRn-mediated persistence, and manufacturability. This is particularly relevant for formats in which Fc effector function is undesirable, including immune-engaging antibodies, CD47 blockers, and antibody-drug conjugates (ADCs). Accordingly, a robust Fc engineering framework enabling complete and transferable effector silencing across antibody modalities is required. We developed Stealth-Body (SB) Fc variants, a fully effector-silenced Fc platform that abolishes Fc-mediated immune engagement while maintaining native-like glycosylation, pharmacokinetics, and manufacturability. Using a CHO cell display system with directed evolution guided by cross-species sequence features from goat IgG, we identified human glycosylated IgG1 variants (SB1, SB5, SB6) that abrogated binding to all human FcγRs and C1q, and to all murine and cynomolgus FcγRs. SB Fc retained pH-dependent FcRn binding, antigen recognition, thermostability, and expression, with in vivo persistence comparable to wild-type IgG1. Incorporation of SB Fc into trastuzumab, rituximab, and ADCs abolished ADCC, ADCP, and CDC, while integration into a CD47-targeting IgG-CD40L fusion protein mitigated hematologic toxicity without impairing immune activation. Collectively, SB Fc variants represent a generalizable, effector-null Fc scaffold that enables complete and transferable silencing of Fc-mediated immune functions while preserving key developability attributes. This platform expands the therapeutic window of antibody therapeutics through precise control of Fc activity across diverse modalities.

PMID 42928316
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PubMedThe New England journal of medicine2026-10-26

Anbenitamab plus HB1801 for HER2-Positive Advanced Breast Cancer.

Wang Jiayu J, Li Huiping H, Xu Fei F, Wu Tao T et al.

The combination of docetaxel, trastuzumab, and pertuzumab (THP) is an established first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. The efficacy and safety of anbenitamab, a HER2-targeted bispecific antibody, plus albumin-bound docetaxel (HB1801) in this context are unknown. In this phase 3, multicenter, open-label, randomized trial conducted in China, we randomly assigned patients with HER2-positive advanced breast cancer in a 1:1 ratio to receive either anbenitamab plus HB1801 or THP. The primary end point was progression-free survival, as assessed by blinded independent central review. Objective response was a secondary end point. A total of 885 patients were enrolled (445 were assigned to receive anbenitamab plus HB1801 and 440 to receive THP). At this prespecified interim analysis (with 401 events [disease progression or death] and a median follow-up of 21.0 months), the estimated 24-month progression-free survival was significantly higher with anbenitamab plus HB1801 than with THP (58.5% vs. 34.4%; hazard ratio for progression or death, 0.46; 95% confidence interval, 0.37 to 0.56; P<0.001). The percentage of patients with an objective response was 87.6% in the anbenitamab group and 73.4% in the THP group. Adverse events of grade 3 or higher occurred in 204 of 444 patients (45.9%) in the anbenitamab group and in 151 of 439 patients (34.4%) in the THP group. Neutropenia was the most common adverse event of grade 3 or higher in both groups (13.1% in the anbenitamab group and 8.4% in the THP group). Adverse events leading to death occurred in 2 patients in each group. Anbenitamab plus HB1801 led to significantly higher progression-free survival than THP among patients with HER2-positive advanced breast cancer. (Funded by Shanghai JMT-Bio Technology and others; HEALER ClinicalTrials.gov number, NCT05838066.).

PMID 42929681
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PubMedCase reports in oncology2026-10-25

Trastuzumab and Pertuzumab Suspected Therapy-Induced Ocular Toxicity in Patient Living with HER2-Positive Advanced Breast Cancer.

Ramagiri Lahari L, Johnson Kai C C KCC, Gatti-Mays Margaret E ME, Davenport Ashley P AP

Trastuzumab and pertuzumab, in combination with chemotherapy, are first-line anti-human epidermal growth factor 2 (HER2) therapies in the treatment of HER2-positive metastatic breast cancer. Although these therapies have been shown to improve the overall survival of patients, they can also be associated with adverse events; ocular toxicities have not been well-documented. This report outlines the case of a patient with a spectrum of new-onset transient ocular symptoms on pertuzumab-trastuzumab combination therapy that improved with cessation of the drug and recurred with trastuzumab monotherapy rechallenge. She developed ocular symptoms 2 years into her treatment course. Her principal ophthalmologic diagnosis was dry eye syndrome of bilateral lacrimal glands and keratoconjunctivitis sicca. Ultimately, she opted for close observation in lieu of continuing therapy. Her staging scans show no evidence of disease, and she denies eye-related symptom recurrence. Given the limited knowledge regarding the long-term ocular adverse events of HER2-targeted therapies, medical oncologists should routinely ask patients about new-onset or worsening ophthalmic symptoms.

PMID 42923999
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