Karen Autio1,2, Martin Oft3. 1. Genitourinary Oncology Service/Melanoma and Immunotherapeutics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. autiok@mskcc.org. 2. Weill Cornell Medicine, New York, NY, USA. autiok@mskcc.org. 3. ARMO Biosciences, Redwood City, CA, USA.
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. 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.
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. 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.
Authors: H Tilg; C van Montfrans; A van den Ende; A Kaser; S J H van Deventer; S Schreiber; M Gregor; O Ludwiczek; P Rutgeerts; C Gasche; J C Koningsberger; L Abreu; I Kuhn; M Cohard; A LeBeaut; P Grint; G Weiss Journal: Gut Date: 2002-02 Impact factor: 23.059
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