Abstract | BACKGROUND: PATIENTS AND METHODS: We investigated the changes in immune effector cells and EGFR pathway biomarkers in 44 patients with operable, advanced stage head and neck squamous cell carcinoma treated with two preoperative doses of either glycoengineered imgatuzumab (GA201; 700 or 1400 mg) or cetuximab (standard dosing) in a neoadjuvant setting with paired pre- and post-treatment tumor biopsies. RESULTS: Significant antitumor activity was observed with both antibodies after just two infusions. Metabolic responses were seen in 23 (59.0%) patients overall. One imgatuzumab-treated patient (700 mg) achieved a 'pathological' complete response. An immediate and sustained decrease in peripheral natural killer cells was consistently observed with the first imgatuzumab infusion but not with cetuximab. The functionality of the remaining peripheral natural killer cells was maintained. Similarly, a pronounced increase in circulating cytokines was seen following the first infusion of imgatuzumab but not cetuximab. Overall, tumor-infiltrating CD3+ cell counts increased following treatment with both antibodies. A significant increase from baseline in CD3+/perforin+ cytotoxic T cells occurred only in the 700-mg imgatuzumab group (median 95% increase, P < 0.05). The most prominent decrease of EGFR-expressing cells was recorded after treatment with imgatuzumab (700 mg, -34.6%; 1400 mg, -41.8%). The post-treatment inflammatory tumor microenvironment was strongly related to baseline tumor-infiltrating immune cell density, and baseline levels of EGFR and pERK in tumor cells most strongly predicted therapeutic response. CONCLUSIONS: These pharmacodynamic observations and relationship with efficacy are consistent with the proposed mode of action of imgatuzumab combining efficient EGFR pathway inhibition with ADCC-related immune antitumor effects. CLINICAL TRIAL REGISTRATION NUMBER: NCT01046266 (ClinicalTrials.gov).
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Authors | S Temam, J Spicer, F Farzaneh, J C Soria, D Oppenheim, M McGurk, A Hollebecque, J Sarini, K Hussain, S Soehrman Brossard, L Manenti, S Evers, P Delmar, L Di Scala, C Mancao, F Feuerhake, L Andries, M G Ott, A Passioukov, J P Delord |
Journal | Annals of oncology : official journal of the European Society for Medical Oncology
(Ann Oncol)
Vol. 28
Issue 11
Pg. 2827-2835
(Nov 01 2017)
ISSN: 1569-8041 [Electronic] England |
PMID | 28950289
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
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Copyright | © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected]. |
Chemical References |
- Antibodies, Monoclonal, Humanized
- Glycoproteins
- EGFR protein, human
- ErbB Receptors
- Cetuximab
- imgatuzumab
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Topics |
- Aged
- Antibodies, Monoclonal, Humanized
(administration & dosage)
- Antibody-Dependent Cell Cytotoxicity
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Carcinoma, Squamous Cell
(drug therapy, immunology, pathology, surgery)
- Cetuximab
(administration & dosage)
- ErbB Receptors
(antagonists & inhibitors, immunology)
- Female
- Follow-Up Studies
- Glycoproteins
(administration & dosage)
- Head and Neck Neoplasms
(drug therapy, immunology, pathology, surgery)
- Humans
- Male
- Middle Aged
- Prognosis
- Prospective Studies
- Survival Rate
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