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Pegylated Interleukin-10: Clinical Development of an Immunoregulatory Cytokine for Use in Cancer Therapeutics

Current Oncology Reports volume 21, Article number: 19 (2019) Cite this article

Abstract

Purpose of Review

Interleukin-10 (IL-10) is a cytokine with anti-inflammatory properties, which induces activation and proliferation of antigen-activated intratumoral CD8+ T cells. This review discusses the evolution of pegylated IL-10 (pegilodecakin) from preclinical investigation through first-in-human studies in oncology.

Recent Findings

Pegilodecakin was evaluated across multiple advanced solid tumors in a large phase 1/1b trial alone and in combination with chemotherapy or anti-PD-1 antibodies. Pegilodecakin monotherapy had immunologic and clinical activity in renal cell carcinoma (RCC) and uveal melanoma. In combination with anti-PD-1 inhibitors, pegilodecakin increased the responses in RCC and lung cancer with efficacy agnostic to PD-L1 status and tumor mutational burden. Pegilodecakin with FOLFOX had activity in pretreated pancreatic cancer, instructing the ongoing randomized phase III trial of the combination versus FOLFOX.

Summary

The increased half-life of pegilodecakin enabled compelling preclinical data for IL-10 which has now been confirmed by clinical activity in a variety of cancers. The ability of pegilodecakin to both exert anti-tumor immunity and inhibit tumor-associated inflammation characterizes the uniqueness of this cytokine therapy.

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Authors and Affiliations

  1. Genitourinary Oncology Service/Melanoma and Immunotherapeutics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Karen Autio

  2. Weill Cornell Medicine, New York, NY, USA

    Karen Autio

  3. ARMO Biosciences, Redwood City, CA, USA

    Martin Oft

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  1. Karen Autio
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Correspondence to Karen Autio.

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Conflict of Interest

Karen Autio has received research funding (paid to her institution) from ARMO Biosciences, Eli Lilly, Pfizer, Merck, GlaxoSmithKline, and CytomX.

Martin Oft is a full-time employee of ARMO Biosciences, a fully owned subsidiary of Eli Lilly and Company.

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This article does summarize human studies performed by the authors and all patients signed informed consent forms approved by their institutions.

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This article is part of the Topical Collection on Evolving Therapies

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Autio, K., Oft, M. Pegylated Interleukin-10: Clinical Development of an Immunoregulatory Cytokine for Use in Cancer Therapeutics. Curr Oncol Rep 21, 19 (2019). https://doi.org/10.1007/s11912-019-0760-z

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  • DOI: https://doi.org/10.1007/s11912-019-0760-z

Keywords

  • IL-10
  • Pegilodecakin
  • AM0010
  • Cytokine
  • Immunotherapy