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

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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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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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