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A phase I study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma

  • PHASE I STUDIES
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Summary

Purpose This phase I study was conducted to determine the safety profile and maximum tolerated dose (MTD) of IMP321, a soluble lymphocyte activation gene-3 (LAG-3) Ig fusion protein and MHC Class II agonist, combined with gemcitabine in patients with advanced pancreatic adenocarcinoma. Patients and methods Patients with advanced pancreatic adenocarcinoma were treated with gemcitabine (1,000 mg/m2)(level 1), gemcitabine (1,000 mg/m2) plus IMP 321 at 0.5 mg (level 2) and 2.0 mg (level 3), respectively. Safety, toxicity, and immunological markers at baseline and post treatment were assessed. Results A total of 18 patients were enrolled to the study, and 17 were evaluable for toxicity. None of the 6 patients who received 0.5 mg IMP321 experienced IMP321-related adverse events. Of the 5 patients who received IMP321 at the 2 mg dose level, 1 experienced rash, 1 reported hot flashes and 2 had mild pain at the injection sites. No severe adverse events previously attributed to IMP321 were observed. No significant differences were observed when comparing pre- and post-treatment levels of monocytes (CD11b+CD14+), conventional dendritic cells (CD11c+) or T cell subsets (CD4, CD8). Conclusions IMP321 in combination with gemcitabine is a well-tolerated regimen. IMP321 did not result in any severe adverse events. No incremental activity observed for the additional IMP 321 to gemcitabine at the dose levels evaluated, likely due to sub-optimal dosing. Immunological markers suggested that higher dose levels of IMP321 are needed for future clinical studies.

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Acknowledgments

The authors would like to acknowledge The Gateway for Cancer Research foundation (P-07-019), Doug Phillips Family, and the Department of Surgery for their financial support of the clinical trial. We acknowledge Immutep S.A. for donating IMP321. We would also like to acknowledge the Siteman Cancer Center Clinical Trials Core (2P30CA901842) and the T32 training grant (5T32CA009621) which supported PS, JH and JM.

Disclosure of potential conflicts of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Andrea Wang-Gillam, Steven Sorscher, Joel Picus, Rama Suresh, Albert C. Lockhart & Benjamin Tan

  2. Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Stacey Plambeck-Suess, Peter Goedegebuure, Jonathan B. Mitchem, John R. Hornick & Williams G. Hawkins

  3. Vascular and Interventional Radiology, University of Virginia Health System, Charlottesville, VA, USA

    Peter O. Simon

  4. Siteman Cancer Center, St. Louis, MO, USA

    Andrea Wang-Gillam, Peter Goedegebuure, Steven Sorscher, Joel Picus, Rama Suresh, Albert C. Lockhart, Benjamin Tan & Williams G. Hawkins

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  1. Andrea Wang-Gillam
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  2. Stacey Plambeck-Suess
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  3. Peter Goedegebuure
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  11. Benjamin Tan
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  12. Williams G. Hawkins
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Corresponding author

Correspondence to Williams G. Hawkins.

Additional information

Andrea Wang-Gillam and Stacey Plambeck-Suess contributed equally to this article.

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Wang-Gillam, A., Plambeck-Suess, S., Goedegebuure, P. et al. A phase I study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma. Invest New Drugs 31, 707–713 (2013). https://doi.org/10.1007/s10637-012-9866-y

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  • DOI: https://doi.org/10.1007/s10637-012-9866-y

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