Abstract A156: GA201 (RG7160) pretreatments and combination therapies improve efficacy without negatively affecting antitumoral ADCC

• Published in: Molecular cancer therapeutics 2011-11, Vol.10 (11_Supplement), p.A156-A156
• Main Authors: Nicolini, Valeria, Herter, Sylvia, Lang, Sabine, Walhauer, Inja, van Puijenbroek, Erwin, Dunn, Claire, Umana, Pablo, Gerdes, Christian A.
• Format: Article
• Language: English
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.TARG-11-A156

GA201 is a humanized and glycoengineered IgG1 antibody which targets EGFR with boosted antibody dependent cell cytotoxicity (ADCC) in phase 2 clinical trials. Pretreatment with corticosteroids and/or anti-histaminics are of normal practice for monoclonal antibody therapy to prevent potential infusion reactions. GA201 follows a premedication regimen of anti-histaminics and hydrocortisone. Due to the dual GA201 mode of action, evaluation on the impact of these drugs on ADCC is critical and was previously assessed preclinically for potential negative impacts on immune effector cells and their capacity to mediate tumor cell killing. Combination phase II studies with GA201 + chemotherapy regimens are currently under investigation in NSCLC as first-line treatment (chemotherapy selection based on histology Cisplatin + gemcitabine for squamous and cisplatin + pemetrexed for non squamous) and in CRC as second-line treatment (FOLFIRI for KRAS-mutant CRC or cetuximab + FOLFIRI for KRAS-wildtype CRC). These combinations and others where tested prior use in the clinics to evaluate preclinical efficacy and their impact on the immune effectors in vitro, and in vivo. Chemotherapy combos showed additive or synergistc effect in anti-tumor efficacy as assessed in orthotopic xenograft models and all pre-medications and chemotherapies tested showed no negative impact on ADCC supporting their combination with GA201 in the clinics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A156.