Current situation of zalutumumab

Rivera, Fernando; Salcedo, Matilde; Vega, N. Bello; Blanco, Yolanda; López, Carlos

doi:10.1517/14712590902932871

Cited by 17 publications

(9 citation statements)

References 58 publications

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“…Zalutumumab is a human mAb with a high affinity to EGFR1 and is characterized by its low immunogenicity which improves its tolerance while retaining the induction of the antibody-dependent cellular toxicity (ADCC) [60,61]. Clinical trials investigating this antibody for the treatment of non-small cell lung cancer (NSCLC) and colorectal cancer were performed.…”

Section: Zalutumumabmentioning

confidence: 99%

“…Clinical trials investigating this antibody for the treatment of non-small cell lung cancer (NSCLC) and colorectal cancer were performed. A first phase I+II trial in patients with recurrent disease reported that this antibody was well tolerated, although a skin rash was reported in over 50% of the study participants [60]. A synergistic effect of combining monoclonal antibodies with chemotherapy has been demonstrated by different working groups.…”

Section: Zalutumumabmentioning

confidence: 99%

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Molecular Targeting Therapy against EGFR Family in Breast Cancer: Progress and Future Potentials

Maennling

Tur

Niebert

et al. 2019

Cancers

159

109

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The epidermal growth factor receptor (EGFR) family contains four transmembrane tyrosine kinases (EGFR1/ErbB1, Her2/ErbB2, Her3/ErbB3 and Her4/ErbB4) and 13 secreted polypeptide ligands. EGFRs are overexpressed in many solid tumors, including breast, pancreas, head-and-neck, prostate, ovarian, renal, colon, and non-small-cell lung cancer. Such overexpression produces strong stimulation of downstream signaling pathways, which induce cell growth, cell differentiation, cell cycle progression, angiogenesis, cell motility and blocking of apoptosis.The high expression and/or functional activation of EGFRs correlates with the pathogenesis and progression of several cancers, which make them attractive targets for both diagnosis and therapy. Several approaches have been developed to target these receptors and/or the EGFR modulated effects in cancer cells. Most approaches include the development of anti-EGFRs antibodies and/or small-molecule EGFR inhibitors. This review presents the state-of-the-art and future prospects of targeting EGFRs to treat breast cancer.

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Section: Zalutumumabmentioning

confidence: 99%

Section: Zalutumumabmentioning

confidence: 99%

Molecular Targeting Therapy against EGFR Family in Breast Cancer: Progress and Future Potentials

Maennling

Tur

Niebert

et al. 2019

Cancers

159

109

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“…This human IgG1 mAb is characterized by high affinity to EGFR and low immunogenicity. The main advantage of zalutumumab is its immunogenicity, which, while improving overall tolerance, does not impair ADCC induction [35]. The efficacy of zalutumumab has been evaluated in incurable HNSCC, where it increased overall survival by 1.5 months versus healthy controls [36].…”

Section: Mabs-based Immunotherapymentioning

confidence: 99%

Clinical value of monoclonal antibodies and tyrosine kinase inhibitors in the treatment of head and neck squamous cell carcinoma

2017

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Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of malignant tumours that affects over 500,000 patients per year. Treatment failure is generally due to the heterogeneity of these tumours and to the serious adverse effects associated with treatment. Immunological system impairment, which is common in HNSCC, further contributes to treatment failure by mediating tumour escape mechanisms. To date, the only clinically approved targeted therapy agent is cetuximab, a monoclonal antibody (mAb) that binds to, and inhibits, epidermal growth factor receptor, which is widely overexpressed in HNSCC. Cetuximab has been proven to induce antibody-dependent cellular cytotoxicity, further magnifying its therapeutic effect. DNA sequencing of HNSCC cells has identified the presence of mutated genes, thus making their protein products potential targets for therapeutic inhibition. Immune mechanisms have been found to have a significant impact on carcinogenesis, thus providing the rationale to support efforts to identify anticancer compounds with immunomodulatory properties. In the context of the rapid development of novel targeted agents, the aim of the present paper is to review our current understanding of HNSCC and to review the novel anticancer agents (mAbs and TKIs) introduced in recent years, including an assessment of their efficacy and mechanisms of action.

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“…Patients in the first cohort received an initial zalutumumab dose of 8 mg/kg, followed by 7 weekly maintenance doses of 4 mg/kg. In the second phase of the study, Zalutumumab was evaluated with three regimens of accelerated RT in association with chemotherapy [36]. A total of 30 patients were enrolled and have completed 16 months of follow-up.…”

Section: The Gen 205 Study Is An Open-label Single-arm Trialmentioning

confidence: 99%

Zalutumumab in head and neck cancer

Schick

Gujral

Richards

et al. 2011

Expert Opinion on Biological Therapy

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Zalutumumab has demonstrated acceptable toxicity in head and neck cancer patients, with rash being the most common adverse event. The toxicity profile makes zalutumumab an attractive option for patients who are heavily pretreated and/or have poor performance status due to concurrent co-morbidities. As the molecule is fully human, the likelihood of hypersensitivity to the drug is low. Zalutumumab may be effective at low concentrations through antibody-dependent cellular cytotoxicity. Current data from Phase I and II trials identify zalutumumab as a promising drug for the treatment of locally advanced head and neck cancer and recent data from a Phase III randomized trial showed encouraging survival results compared with best supportive care. Results from other ongoing Phase III trials will provide clarification on zalutumumab as a treatment option. The clinical development of this compound has been suspended from June 2011 until a development and commercialization partner is found.

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Current situation of zalutumumab

Cited by 17 publications

References 58 publications

Molecular Targeting Therapy against EGFR Family in Breast Cancer: Progress and Future Potentials

Molecular Targeting Therapy against EGFR Family in Breast Cancer: Progress and Future Potentials

Clinical value of monoclonal antibodies and tyrosine kinase inhibitors in the treatment of head and neck squamous cell carcinoma

Zalutumumab in head and neck cancer

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