Erbitux (cetuximab) / Eli Lilly 
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  • ||||||||||  Journal, IO biomarker:  BCL-XL inhibitors enhance the apoptotic efficacy of BRAF inhibitors in BRAFV600E colorectal cancer. (Pubmed Central) -  Mar 6, 2024   
    Combining encorafenib with DT2216 significantly increased apoptosis induction in vitro, while combining encorafenib with AZD0466 was well tolerated in mice and further reduced growth of BRAFV600E CRC xenografts compared to either agent alone. Collectively, these findings demonstrate that combined BRAF and BCL-XL inhibition significantly enhances apoptosis in pre-clinical models of BRAFV600E CRC and is a combination regimen worthy of clinical investigation to improve outcomes for these patients.
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Unravelling intra-tumor phenotypic heterogeneity in colorectal cancer organoids (Section 11) -  Mar 5, 2024 - Abstract #AACR2024AACR_9789;    
    We performed in total scRNAseq for 7 mCRC samples (4 wt; 3 kras) in different growth media: normal growth medium (supplemented with EGF) (n=1); medium without EGF (noEGF) (n=7); or treated with Cetuximab (CTX, a clinically approved monoclonal antibody against EGFR) (n=7)...This suggests that this WNT-associated subpopulation could be contributing, at least in part, to CTX tolerance or resistance. Our results show promising potential to help unravel basic features of intra-tumor heterogeneity both in basal conditions and upon treatment, and possibly to find new therapeutic targets.
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Integrating PDX GBM in vivo models with patient history and whole exome sequencing: Advancing relevance and precision in preclinical studies (Section 10) -  Mar 5, 2024 - Abstract #AACR2024AACR_9754;    
    By contrast, GBM46 from a patient with prior treatment with TMZ, OSI-774, radiation, and BCNU, exhibited a 58% increase in overall lifespan when treated with TMZ alone...Models with defined clinical treatment history and WES data allows for testing new agents in models that more closely resemble the clinical development path for a given new agent and aids in deciphering factors influencing therapeutic resistance. These models have the potential to reshape preclinical research paradigms, accelerating the translation of promising therapeutic agents increasing the likelihood of clinical benefit for patients with glioblastoma multiforme.
  • ||||||||||  AM105 / AbClon
    AM105: A novel bispecific antibody with Anti 4-1BB affibodies and EGFR antibody (Section 41) -  Mar 5, 2024 - Abstract #AACR2024AACR_7748;    
    Our findings collectively establish AM105 as a potent therapeutic agent with strong anti-tumor T cell activity. The unique 4-1BB based Affibodies (AffiMab format) of AM105 holds promise for addressing the limitations of current bispecific antibodies, positioning it as a potential breakthrough in cancer immunotherapy.
  • ||||||||||  DXC004A / Hangzhou DAC Biotech
    DXC004A, a novel EGFR antibody-tubulysin analog conjugate demonstrated potential to broaden therapeutic opportunities for non-small cell lung cancer (Section 23) -  Mar 5, 2024 - Abstract #AACR2024AACR_6709;    
    A phase 2 clinical trial has confirmed that Nimotuzumab combined with concurrent chemoradiation therapy (radiation concurrent with docetaxel and cisplatin, CCRT) was well tolerated for locally advanced squamous cell lung cancer...Moreover, the combination of DXC004A with Cisplatin exhibited significantly better activities than that of Nimo-CCRT combination, DXC004A or cisplatin alone, in vitro and in vivo, which might solve the predicament of poor efficacy of Nimo-CCRT combination therapy. This synergy results suggested that DXC004A plus cisplatin would possibly be a new adjuvant therapy for non-small cell lung cancer in further clinical studies.
  • ||||||||||  Mekinist (trametinib) / Novartis, BeiGene, Erbitux (cetuximab) / Eli Lilly, EMD Serono
    EGFR inhibitors increase LGR5 expression and enhance potency of LGR5 antibody-drug conjugates targeting colorectal cancer stem cells (Section 23) -  Mar 5, 2024 - Abstract #AACR2024AACR_6708;    
    Notably, treatment with EGF, MEK1/2 inhibitor trametinib, and EGFR-directed siRNA all resulted in concomitant reduction in EGFR and LGR5 protein levels, suggesting EGFR and LGR5 are co-degraded...Furthermore, we showed EGFR-LGR5 interaction is enhanced by treatment with the EGFR-targeting mAb, cetuximab (CTX)...Importantly, we showed CTX significantly enhanced the potency of LGR5 ADCs incorporating different classes of cytotoxic payloads. These results suggest combining LGR5 ADCs with EGFR inhibitors may be a more effective approach for the treatment of CRC and eliminating CSCs to overcome resistance and relapse.
  • ||||||||||  Organoids to predict treatment response in metastatic colorectal cancer (OPTIC) (Section 45) -  Mar 5, 2024 - Abstract #AACR2024AACR_6462;    
    OPTIC will enhance the clinical application of PDOs by defining thresholds for PDO sensitivity and analyzing the diagnostic power for different treatments. To enable personalized treatment in clinical practice, PDO screening should guide mCRC treatment and result in enhanced chance of response and reduced over- and mistreatment.
  • ||||||||||  Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Examples of translational preclinical models to mimic cancer drug resistance (Section 10) -  Mar 5, 2024 - Abstract #AACR2024AACR_5899;    
    Following this successful approach, we initiated the development of a novel ER2-expressing PDX breast tumor model, resistant to hormone therapy by repeated Fulvestrant treatment...We confirmed the key role of a KRAS mutation in cetuximab resistance.Syngeneic model: In this model, animals were dosed with anti-PDL1 as first line of treatment...During the second line of treatment with a tyrosine kinase inhibitor, we observed an antitumor activity on Avastin resistant animals.In each of these case studies, we developed a novel tumor-resistant mechanism model. In some tumor models, we showed the added value of treating animals with new drugs as second line treatment, after establishing resistance to the first line standard of care treatment.
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Characterization of EGFR ectodomain mutation in acquired resistance to cetuximab in colorectal cancer (Section 26) -  Mar 5, 2024 - Abstract #AACR2024AACR_5352;    
    Further structural, and functional characterization is underway for this ectodomain mutation that confers resistance to cetuximab and will be shared during the meeting. These findings necessitate the need for additional treatment strategies for a subset of subjects with mCRC who do not respond to treatment with cetuximab/panitumumab and MM-151.
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono, Vectibix (panitumumab) / Amgen
    Comparative spatial transcriptomic analysis of monoclonal antibodies targeting the same molecule: A comparison between cetuximab and panitumumab (Section 34) -  Mar 5, 2024 - Abstract #AACR2024AACR_4806;    
    In the examination of the distribution patterns of two distinct therapeutic antibodies targeting EGFR within cancer tissues, a notable observation was made: while the cell types exhibited similarity, the associated genes demonstrated divergence, with different degrees of alignment with the intended target. This analytical approach, scrutinizing the distribution of different antibodies within tissue sharing a common target, holds promise as a widely applicable method for elucidating divergent therapeutic effects.
  • ||||||||||  Akalux (cetuximab sarotalocan) / Rakuten Medical, Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Reduction in photoimmunotherapy-induced edema with COX-2 inhibition: Combatting clinically relevant adverse events without compromising efficacy (Section 5) -  Mar 5, 2024 - Abstract #AACR2024AACR_4179;    
    Preclinical characterization of SM2235 shows promising in vivo efficacy against EGFR+ human cancers, regardless of KRAS mutation, with a favorable safety profile marked by minimal skin toxicity. ASP-1929 photoimmunotherapy (PIT), an investigational drug-device combination, consists of an epithelial growth factor receptor (EGFR)-targeting drug, cetuximab, conjugated to a light-activatable dye, IRDye
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Autocrine HGF maturation as a targetable regulatory step in cetuximab resistance in colorectal cancer (Section 26) -  Mar 5, 2024 - Abstract #AACR2024AACR_3996;    
    Additionally, HAI-1, an endogenous inhibitor of HGF proteases, (i) was downregulated in CRC, (ii) exhibited increased genomic methylation that correlated with poor prognosis, (iii) HAI-1 expression correlated with cetuximab response in a panel of cancer cell lines, and (iv) exogenous addition of recombinant HAI-1 overcame cetuximab resistance in CC-HGF cells. Thus, we describe a targetable, autocrine HAI-1/Protease/HGF/MET axis in cetuximab resistance in CRC.
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer
    DUSP4 loss enhances resistance to encorafenib plus cetuximab in BRAF mutant colorectal cancer (Section 26) -  Mar 5, 2024 - Abstract #AACR2024AACR_3990;    
    These results demonstrate that DUSP4 regulates ERK/MAPK signalling in BRAF mutant CRC cell lines and that loss of DUSP4 promotes resistance to encorafenib plus cetuximab treatment. These findings warrant investigation of DUSP4 expression status as a predictive biomarker of encorafenib+cetuximab response in patient samples.
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Molecular and therapeutic characterization of a large-scale collection of metastatic colorectal cancer patient-derived xenografts and matched organoids for translational oncology (Section 9) -  Mar 5, 2024 - Abstract #AACR2024AACR_3149;    
    A PDXT-based population trial with the clinically approved anti-EGFR antibody cetuximab was performed in 116 PDXTs, revealing variable sensitivities that were consistent with clinical response biomarkers and with tumor growth changes in 79 matched PDXs...Results were finally validated in PDXs.To our knowledge, this is the first large-scale study in which a systematic comparison of molecular and therapeutic profiles between PDXT-PDX pairs was attempted. As a publicly available resource, XENTURION will offer a knowledge base of disseminatable methods, resources and information to streamline preclinical studies and accelerate new treatments for patients with mCRC.
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono, Opdivo (nivolumab) / BMS, Imbruvica (ibrutinib) / AbbVie, J&J
    Trial completion date, Trial primary completion date, Combination therapy, IO biomarker, Metastases:  Trial of Ibrutinib Combined With Nivolumab or Cetuximab to Treat Recurrent/Metastatic HNSCC (clinicaltrials.gov) -  Mar 5, 2024   
    P2,  N=5, Active, not recruiting, 
    Our real-world results indicated that pembrolizumab regimen is a promising treatment in patients with R/M HNSCC. Trial completion date: May 2024 --> May 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono, Tecentriq (atezolizumab) / Roche
    Journal, Tumor cell:  Direct Functionalization of Polysaccharide-Based Xylan Phenyl Carbonate Nanoparticles with Tumor Cell Specific Antibodies. (Pubmed Central) -  Mar 4, 2024   
    By quartz crystal microbalance experiments with dissipation monitoring (QCM-D), flow cytometry assays, and confocal laser scanning microscopy imaging it is demonstrated that the functionalized XPC-NP specifically bind to cells carrying the corresponding antigens. Moreover, the NP retain the antibody specific bioactivities (growth inhibition for CTX and induction of T-cell cytotoxicity for ATZ).
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Observational data, Retrospective data, Journal:  Risk factors for oral mucositis in patients with solid tumors under treatment with cetuximab: a retrospective cross-sectional study. (Pubmed Central) -  Mar 4, 2024   
    Moreover, the NP retain the antibody specific bioactivities (growth inhibition for CTX and induction of T-cell cytotoxicity for ATZ). Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution.
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Journal:  3D modeling of normal skin and cutaneous squamous cell carcinoma. A comparative study in 2D cultures, spheroids, and 3D bioprinted systems. (Pubmed Central) -  Mar 1, 2024   
    All models were also functionally assessed by cetuximab (CTX) response testing with the MTS assay...This study underscores the potential of 3D multicellular models in elucidating drug responses and gaining a better understanding the intricate interplay of cellular components within the tumor microenvironment. Developing the multicellular 3D tumor model paves the way for new research critical to advancing fundamental cancer research and future clinical applications, particularly drug response testing.
  • ||||||||||  Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Enrollment open:  Treatment of Relapsed/Refractory Intracranial Glioma in Patients Under 22 Years of Age (clinicaltrials.gov) -  Feb 29, 2024   
    P1/2,  N=20, Recruiting, 
    Developing the multicellular 3D tumor model paves the way for new research critical to advancing fundamental cancer research and future clinical applications, particularly drug response testing. Not yet recruiting --> Recruiting
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Trial primary completion date, Metastases:  Neoadjuvant Cetuximab + Chemotherapy Combined With Short-course Radiotherapy (clinicaltrials.gov) -  Feb 25, 2024   
    P=N/A,  N=51, Recruiting, 
    Not yet recruiting --> Recruiting Trial primary completion date: Jun 2023 --> Aug 2024
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Journal:  Impact of antibody architecture and paratope valency on effector functions of bispecific NKp30 x EGFR natural killer cell engagers. (Pubmed Central) -  Feb 23, 2024   
    For EGFR-positive tumor targeting, humanized antigen-binding domains of therapeutic antibody cetuximab were used...However, the fusion of sdAbs can have a slight impact on the NK cell release of immunomodulatory cytokines, as well as on the pharmacokinetic profile of the NKCE due to unfavorable spatial orientation within the molecule architecture. Ultimately, our findings reveal novel insights for the engineering of potent NKCEs triggering the NKp30 axis.