Combinations of immunotherapy and vascular endothelial growth factor (VEGF) inhibitors have been proven to effective at improving survival for people with advanced or metastatic renal cell carcinoma (RCC). However, the role of a cytokine called interleukin-10 (IL-10) has been shown to enhance immunotherapy-induced anti-cancer activity.
In this phase 1 trial, the safety, tolerability and preliminary efficacy of an IL-10 cytokine attached to polyethylene glycol (pegylated IL-10) called pegilodecakin was tested on its own and in combination with either an anti-PD-1 drug (pembrolizumab or nivolumab) or a VEGF inhibitor (pazopanib) in patients with metastatic RCC who had failed at least one prior treatment, including immunotherapy, IL-2 and/or interferon.
Pegilodecakin was well tolerated and the rate of treatment discontinuation due to side effects was very low. Most serious or life-threatening side effects were not drug-related and immune-related side effects did not increase in the pegilodecakin plus anti-PD-1 arm.
43% of patients responded to treatment and their cancer reduced in size. The average time to when the drug stopped working and the cancer started growing again was 13.9 months and there was a 61% probability of survival at 2 years with pegilodecakin plus immunotherapy. Moreover, the pazopanib plus pegilodecakin group had a response rate of 33%.
In conclusion, pegilodecakin should continue to be evaluated in phase III trials as part of a combination with immunotherapy or as a triple combination with immunotherapy and a VEGF inhibitor. Furthermore, evaluation of pegilodecakin as a neoadjuvant triple combination in patients with locally advanced RCC may give a better understanding of the responses of tumours to such therapy. If a high response rate is achieved, it may improve the effectiveness of treatments in such patients.