Necitumumab (Imc-11f8), A Recombinant Human Anti Egfr Antibody, Increases The Antitumor Effects Of Cisplatin/Paclitaxel In Human Nsclc Xenograft Models

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Epidermal growth factor receptor (EGFR) targeted antibodies may have a role in the treatment of non-small cell lung cancer (NSCLC), based on preclinical and clinical data. Here we have demonstrated a significant benefit of adding necitumumab, a recombinant human IgG1 antibody targeting EGFR, to cisplatin+paclitaxel administered at its maximum tolerated dose, in subcutaneous xenograft tumor models established in nu/nu athymic mice with A549 or NCI-H1650 NSCLC cell lines. Necitumumab monotherapy or cisplatin+paclitaxel therapy inhibited xenograft tumor growth with a T/C% of 47 and 63, respectively in A549 tumor model. A similar anti tumor effect was seen in NCI-H1650 xenograft tumors treated with necitumumab monotherapy or cisplatin+paclitaxel therapy with a T/C% of 37 and 50, respectively. Furthermore, the combination of necitumumab with cisplatin+paclitaxel significantly inhibited tumor growth with a magnitude greater than any of the therapies alone in A549 xenograft tumors with a T/C% of 33 and in NCI-H1650 xenograft tumors with a T/C% of 18. Combination treatment resulted in partial regressions (3 out of 9 mice) in A549 and maximum tumor regressions (10 out of 12) in NCI-H1650. Chi-Squared test for all animals in the treatment groups showed p=0.02 in A549 and p=3.0E-08 in NCI-H1650 xenograft tumors. In vitro analysis on A549 and NCI-H1650 cell lines treated with cisplatin+paclitaxel, with/without necitumumab (5 μg/ml) demonstrated that this combination benefit was associated with the increased apoptotic index in both models. Cell cycle arrest during combination therapy was also observed as an increase in the percentage of cells in G2/M phase in A549 and S or G2/M phase in NCI-H1650 cell lines. We are further utilizing SABiosciences PCR arrays to demonstrate combination benefit related gene function in apoptosis, cell cycle signaling pathways and drug specific biomarkers in both A549 and NCI-H1650 cell lines. Thus our results demonstrate the potential utility of necitumumab for enhancing the efficacy of cytotoxic chemotherapy in both in A549 and NCI-H1650 cell lines and xenograft tumors models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5030. doi:10.1158/1538-7445.AM2011-5030