Pegilodecakin as monotherapy or in combination with anti-PD-1 or tyrosine kinase inhibitor in heavily pretreated patients with advanced renal cell carcinoma (RCC): Final results of cohorts A, G, H, and I of IVY Phase I study.

Interleukin (IL)-10 has anti-inflammatory and CD8+ T-cell-stimulating properties. Pegilodecakin (pegylated recombinant human IL-10) induces intra-tumoral antigen specific CD8+T-cells and upregulates IFNγ and Major Histocompatibility Complex (MHC) I and II.

Pegilodecakin has single-agent activity with manageable toxicity in advanced renal cell cancer (aRCC) (data cutoff 24 March 2016). Pegilodecakin with pembrolizumab or nivolumab revealed clinical activity in aRCC (data cutoff 1 July 2018). Here, we report for the first time the results of pegilodecakin+ pazopanib, and final results for monotherapy and long-term follow-up with pegilodecakin+ anti-PD-1 inhibitors (data cutoff 19 February 2019). Phase 1/1b multi-cohort dose escalation IVY study enrolled 353 patients. Sixty-six patients with aRCC were treated with pegilodecakin alone or with pazopanib or anti-PD-1 inhibitor in cohorts A, G, H, and I (data cutoff 19 February 2019). Primary endpoints included safety and tolerability. Secondary end point was tumor response by immune-related response criteria (irRC). Pegilodecakin plus nivolumab or pembrolizumab yielded median progression-free survival (mPFS) of 13.9 months and 6-month PFS probability of 60%, 76% 1-year OS probability, and 61% 2-year OS probability. Pegilodecakin monotherapy produced mPFS of 1.8 months, 6-month PFS probability 25%, 1-yr OS 50%, and 2-yr OS 17%. Median OS was not reached in both combinations. Objective response rates (ORR) were 33% with pazopanib and 43% with anti-PD-1. Most common Grade 3/4 TRAEs included anemia, thrombocytopenia, and hypertriglyceridemia. In these heavily pretreated RCC cohorts of IVY, pegilodecakin+anti-PD-1 inhibitor showed promising clinical activity. Safety profile of pegilodecakin alone and with anti-PD-1 inhibitors was consistent as previously reported. This article is protected by copyright. All rights reserved.

International journal of cancer. 2021 Mar 12 [Epub ahead of print]

Nizar M Tannir, Kyriakos P Papadopoulos, Deborah J Wong, Raid Aljumaily, Annie Hung, Manuel Afable, Jong Seok Kim, David Ferry, Alexandra Drakaki, Johanna Bendell, Aung Naing

Anderson Cancer Center, Houston, TX., START Center for Cancer Care, San Antonio, TX., University of California Los Angeles (UCLA), CA., Stephenson Cancer Center of the University of Oklahoma and Sarah Cannon Research Institute, Oklahoma City, OK., Eli Lilly and Company, Indianapolis, IN., Eli Lilly and Company, New York City, NY., Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN.

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