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cetuximab (Lupitux / Cetuxa / ENZ124)

✓ Approved

Lupin Limited · EGFR · 单克隆抗体

什么是 cetuximab？

cetuximab 是一种单克隆抗体，由Lupin Limited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Lupitux, Cetuxa, ENZ124
公司Lupin Limited
药物类别单克隆抗体, 抗体
分子靶点EGFR
给药途径Injectable (Others), Intravenous (IV)
状态Approved
来源： ClinicalTrials.gov, Lupin Limited

作用机制

分子靶点

cetuximab 作用于 1 个分子靶点：

EGFRepidermal growth factor receptor (ERBB1, NNCIS)
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

cetuximab 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)Head and neck cancer metastatic✓ Approved

相关研究文献

PubMedMicrobiology and immunology2026-10-25

Monocyte- and Macrophage-Mediated Antibody Sequestration Attenuates Anti-Epidermal Growth Factor Receptor Antibody Efficacy in the Tumor Microenvironment.

Shi Hao H, Komohara Yoshihiro Y, Yasunaga Masahiro M

Tumor-associated monocytes and macrophages are abundant in the tumor microenvironment (TME) and can influence the therapeutic accessibility of antibody drugs. However, the impact of macrophage-mediated antibody sequestration on the therapeutic efficacy of anti-epidermal growth factor receptor (EGFR) therapy remains unclear. This study aimed to assess whether monocytes and macrophages attenuate anti-EGFR therapeutic efficacy by sequestering antibodies. We established a transwell-based co-culture platform using human THP-1 monocytes or macrophages and EGFR-positive DiFi colorectal cancer cells to evaluate macrophage-associated antibody sequestration. In vivo xenograft assays, flow cytometric uptake analyses and inhibitor-based functional studies were performed using the anti-EGFR monoclonal antibodies cetuximab and panitumumab. Xenograft models co-implanted with THP-1 cells demonstrated attenuated responses to anti-EGFR antibodies compared to tumor-only models. Monocytes and macrophages significantly reduced the growth-inhibitory effects of cetuximab and panitumumab in co-culture. Antibody uptake was increased in THP-1 cells and THP-1-derived macrophages. Fc receptor blockade and uptake-associated inhibitors partially suppressed antibody uptake and restored antibody-mediated anti-tumor activity, suggesting the involvement of FcγR-dependent and FcγR-independent pathways. Monocyte- and macrophage-mediated antibody sequestration attenuates anti-EGFR therapeutic efficacy by reducing antibody accessibility to tumor cells. The established co-culture platform provides a useful bioanalytical assay system to screen and evaluate antibody accessibility and macrophage-associated sequestration during the preclinical development of antibody therapeutics.

PMID 42922440
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PubMedInternational journal of clinical and experimental pathology2026-10-23

Fascin-1 expression in advanced colorectal cancer is associated with the treatment efficacy of cetuximab.

Lu Hua-Jun HJ, Lv Guo-Xiao GX, Ren Guo-Chao GC, Shao Jun-Kang JK et al.

Although several studies have reported that Fascin-1 is upregulated in colorectal cancer and promotes tumor progression, its relationship with therapeutic efficacy in patients with colorectal cancer remains unclear. This study aimed to investigate the effect of Fascin-1 protein expression on the efficacy of cetuximab treatment in patients with advanced colorectal cancer (CRC). Immunohistochemical (IHC) staining was used to evaluate the protein expression of Fascin-1 in tissues from 40 patients with advanced CRC. The RECIST criteria were applied to evaluate the efficacy of cetuximab-targeted therapy in CRC patients. Among the 40 advanced CRC patients treated with cetuximab, 12 (30%, 12/40) achieved an objective response, and 28 (70%, 28/40) achieved disease control. IHC results revealed that 18 out of 40 CRC tissues (45%, 18/40) were positive for the Fascin-1 protein. Analysis of the relationship between Fascin-1 expression and treatment efficacy revealed that the objective response rate (ORR) in Fascin-1-positive CRC patients was 11.1% (2/18), which was significantly lower than that in Fascin-1-negative patients (45.5%, 10/22) (P=0.018). Similarly, the disease control rate (DCR) in Fascin-1-positive patients was 50.0% (9/18), which was also significantly lower than that of Fascin-1-negative patients (86.4%, 19/22) (P=0.013). Multiple logistic regression analysis revealed that Fascin-1 positivity was an independent factor associated with failure to achieve an objective response (odds ratio (OR)=6.667; 95% confidence interval (CI): 1.227-36.226; P=0.028) and failure to achieve disease control (OR=7.342; 95% CI: 1.068-50.456; P=0.043). ROC curve analysis revealed that Fascin-1 positivity predicted failure to achieve an objective response, with an area under the curve (AUC) value of 0.702 (95% CI: 0.531-0.874; P=0.045), and failure to achieve disease control, with an AUC value of 0.714 (95% CI: 0.538-0.890; P=0.034). Survival analysis revealed that Fascin-1 positivity was significantly associated with reduced 1-year progression-free survival (PFS) in these patients (P=0.003). Fascin-1 expression status is significantly correlated with the efficacy of cetuximab treatment. Combined intervention against Fascin-1 may be an effective strategy for improving the outcome of patients with RAS wild-type advanced CRC.

PMID 42908535
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PubMedThe Journal of experimental medicine2026-10-23

Antigen-independent BCR signals limit differentiation and survival of IgM antibody-secreting cells.

Zhang Ting-Ting TT, Camp Nathan N, Asher Gregory D GD, Romani Ameena A et al.

IgM contributes to early and durable humoral immunity, yet the mechanisms governing human IgM plasma cell (PC) maturation and persistence remain unknown. Here, using an ex vivo human B cell system, we found that IgM B cell receptor (BCR) signaling restricts IgM antibody-secreting cell (ASC) differentiation and survival. Using CRISPR-mediated gene disruption and pharmacologic inhibition, we show that surface BCR and its proximal signaling components, particularly SYK, suppressed induction of IRF4 and PRDM1, thereby restraining PC differentiation. Concurrently, ligand-independent BCR signaling increased basal calcium flux and apoptosis in IgM plasmablasts. Inhibition of BCR-proximal signaling also increased PC numbers and persistence after in vivo engraftment. Leveraging this mechanistic insight, we demonstrated that SYK KO in engineered PCs (ePCs) significantly improved output and in vivo durability of IgM-cetuximab-secreting ePCs. Together, these findings reveal IgM-BCR signaling as a previously unrecognized negative regulator of human IgM PC differentiation and survival and show that inhibition of BCR-proximal pathways can improve IgM-based cellular immunotherapies.

PMID 42911265
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PubMedFrontiers in immunology2026-10-23

Trifunctional antibody fusion proteins for targeted co-delivery of 4-1BBL with IL-15 or IL-21 to enhance antitumor immune responses.

Möller Annika M AM, Baumann Felix F, Pütter Max M, Xie Meng M et al.

Antibody fusion proteins incorporating immunomodulatory molecules, such as cytokines of the common γ-chain receptor family and costimulatory members of the TNF superfamily, hold great potential for cancer immunotherapy, with many candidates already advancing into clinical studies. However, the efficacy as single agent with one payload is limited and combinatorial approaches are required to fully exploit their immunomodulatory potential. Here, we describe a novel format of a trifunctional antibody fusion protein, composed of a tumor-directed Fab antibody fragment, specific for the fibroblast activation protein (FAP), fused to single-chain 4-1BBL in combination with either IL-15 connected to an IL-15Rα fragment or IL-21. Binding to target cells was confirmed, and activity was assessed on activated PBMCs either bound to target cells or in an untargeted setting. Combinatorial effects enhancing IFN-γ release were found to be targeting-dependent for both trifunctional antibody fusion proteins and superior to the activity observed with combined bifunctional antibody-fusion proteins carrying single payloads. In contrast, significant combined activity enhancing granzyme B expression was observed only for the trifunctional fusion protein containing sc4-1BBL/IL-21 and appeared to be targeting-independent. In 3D coculture settings of fibroblast spheroids and PBMCs, both trifunctional fusion proteins enhanced the cytotoxic effect of an EGFR-directed T cell engager (TCE) and cetuximab (CTX), whereby sc4-1BBL/IL-15 was more effective than sc4-1BBL/IL-21, and comparable effects were obtained by the respective bifunctional antibody-cytokines. The activity of antibody fusion proteins containing IL-15 was associated with strong activation of CD8+T cells, CD3+CD56+ T cells and NK cells, as well as enhanced proliferation, particularly in combination with TCE, expanding CD8+ T cells and NKT-like cells. Activation by fusion proteins containing IL-21 became mainly apparent in combination with TCE on CD8+ T cells and with CTX on NK cells, while proliferation was restricted to NK cells. Thus, the trifunctional antibody fusion proteins presenting sc4-1BBL/IL-15 and sc4-1BBL/IL-21 exhibit distinct patterns of combined activity and immune cell stimulation, both demonstrating combinatorial potential with TCE and CTX.

PMID 42909080
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PubMedClinical colorectal cancer2026-10-22

Irinotecan Plus Cetuximab Rechallenge Versus Trifluridine/Tipiracil Plus Bevacizumab as Third-Line Treatment in Circulating Tumor DNA-Selected Metastatic Colorectal Cancer (ROMANCE Trial).

D'Agata Alessandra Pia AP, Pellizzari Gloria G, Martini Giulia G, Ghidini Michele M et al.

In patients with RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC), anti-epidermal growth factor receptor (EGFR) monoclonal antibodies combined with chemotherapy represent an established first-line option and may provide clinically meaningful tumor shrinkage. However, acquired resistance may develop through the emergence of mechanism/s of acquired resistance. After progression to first- and second-line regimens, the prognosis of patients with mCRC remains poor. Available later-line options exhibit a cytostatic activity and are associated with limited objective response rate (ORR). Of note, the dynamic decay of resistant subclones after withdrawal of EGFR blockade supports the rationale to explore anti-EGFR rechallenge therapy. ROMANCE trial is a multicenter, randomized phase II study. Overall, 150 patients with mCRC with circulating tumor RAS/BRAF/EGFR/PIK3CA exon 20/MAP2K1/MET WT and HER2 nonamplified (negative hyperselected tumors) mCRC, at baseline liquid biopsy, will be randomized 1:1 to irinotecan plus cetuximab rechallenge compared with trifluridine/tipiracil plus bevacizumab as third-line therapy. The primary endpoint is ORR assessed by Response Evaluation Criteria in Solid Tumors 1.1 by blinded independent central review; secondary endpoints include progression-free survival, overall survival, safety, and quality of life. Given the limited ORRs achieved with currently available options after second-line treatment for refractory mCRC, strategies capable of inducing clinically meaningful tumor shrinkage are urgently required. ROMANCE will evaluate whether cetuximab plus irinotecan retreatment can improve ORR compared with standard third-line trifluridine/tipiracil plus bevacizumab in patients with circulating tumor DNA-negative hyperselected mCRC and will clarify the role of anti-EGFR rechallenge in the continuum of care of refractory mCRC. This trial is registered at clinicaltrials.gov (NCT07381764).

PMID 42907240
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PubMedOncology2026-10-22

Secondary metastasis resection after biomarker-stratified first-line treatment of metastatic colorectal carcinomaInterim analysis of the IVOPAK II study with a risk-benefit assessment of secondary metastatic resection.

Wein Axel A, Merkel Susanne S, Eckstein Markus M, Siebler Juergen J et al.

The IVOPAK II study (Interdisciplinary Care with Quality Control in Palliative Treatment of Colorectal Cancer) prospectively evaluated the risk (postoperative complications, mortality) and benefit (overall survival) of multimodal treatment with secondary metastasis resection for initially nonresectable metastatic colorectal carcinoma. A total of 40 patients from 10 centers were enrolled. Patients with quintuple wildtype (K-RAS, N-RAS, BRAF, PIK3CA, ERBB2, MSS) received FOLFIRI plus cetuximab, while patients with RAS-mutation (K-RAS or N-RAS, MSS) received FOLFIRI plus bevacizumab. CT scans were presented at two-month intervals to the interdisciplinary tumor board at the University Hospital Erlangen to assess potentially curative secondary metastatic resection. After a median follow-up of 32 months, outcomes of the multimodally (chemotherapy treatment plus metastasis resection) and the palliatively (only chemotherapy treatment) treated patients were compared. The rate of secondary metastasis resection was 45% (18/40). Overall survival was significantly longer in the multimodal treatment group compared to the palliative treatment group (median 61 vs. 22 months, p=0.002), this also applied to progression-free survival (median 39 vs. 11 months, p=0.018). Clavien-Dindo grade ≥3 morbidity occurred in 28% (5/18) of patients, and 90-day mortality was 6% (1/18). Univariate analyses revealed a significant improvement in overall survival among patients with ECOG performance status 0, solitary metastatic site and multimodal treatment. In multivariate analysis, the ECOG performance status proved to be an independent prognostic factor. Following palliative biomarker-stratified first-line treatment for nonresectable metastatic colorectal carcinoma, the multimodal approach with secondary metastatic resection demonstrated a significant survival benefit.

PMID 42905650
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