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A phase I trial of intravenous infusion of ONYX-015 and enbrel in solid tumor patients

Cancer Gene Therapy volume 14, pages 885–893 (2007)Cite this article

Abstract

ONYX-015 is an attenuated chimeric human group C adenovirus, which preferentially replicates in and lyses tumor cells that are p53 negative. The purpose of this phase I, dose-escalation study was to determine the safety and feasibility of intravenous infusion with ONYX-015 in combination with enbrel in patients with advanced carcinoma. Enbrel is a recombinant dimer of human tumor-necrosis factor (TNF)-α receptor, previously shown to reduce the level of functional TNF. Nine patients, three in each cohort received multiple cycles of ONYX-015 infusion (1 × 1010, 1 × 1011 and 1 × 1012 vp weekly for 4 weeks/cycle) in addition to subcutaneous enbrel (only during cycle 1) injections per FDA-indicated dosing. Of the nine patients, four had stable disease. No significant adverse events were attributed to the experimental regimen, confirming that enbrel can be safely administered along with oncolytic virotherapy. Two of the three patients in cohort 3 had detectable viral DNA at days 3 and 8 post-ONYX-015 infusion. Their detectable circulating viral DNA was markedly higher during cycle 1 (with enbrel coadministration) as compared with cycle 2 (without enbrel) at the same time points. Area under the curve determinations indicate a marked higher level of TNF-α induction and accelerated clearance at cycle 2 in the absence of enbrel. Further assessment is recommended.

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Acknowledgements

We thank Viviana Mangual (Mary Crowley Medical Research Center, Dallas, TX, USA) for her technical assistance in performing the TNF-α ELISA and quantitative PCR analysis of ONYX-015 genome. This study is supported in part by the Baylor Sammons Cancer Center Research Fund.

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Authors and Affiliations

  1. Mary Crowley Medical Research Center, Dallas, TX, USA

    J Nemunaitis, N Senzer, S Sarmiento, Y-A Zhang, R Arzaga, B Sands & A W Tong

  2. Texas Oncology PA, Dallas, TX, USA

    J Nemunaitis & N Senzer

  3. Baylor Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA

    J Nemunaitis, N Senzer, P Maples & A W Tong

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  1. J Nemunaitis
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  2. N Senzer
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Correspondence to J Nemunaitis.

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Nemunaitis, J., Senzer, N., Sarmiento, S. et al. A phase I trial of intravenous infusion of ONYX-015 and enbrel in solid tumor patients. Cancer Gene Ther 14, 885–893 (2007). https://doi.org/10.1038/sj.cgt.7701080

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