Experimental Drug Shows Promise in Treating Lung and Kidney Cancer

A new study has found that patients with non-small cell lung cancer (NSCLC) and kidney cancer may benefit from pegilodecakin, a drug currently in clinical trials. Conducted by researchers from The University of Texas MD Anderson Cancer Center, this work found that when used in concert with pembrolizumab and nivolumab (two leading anti-PD-1 monoclonal antibodies), pegilodecakin was had therapeutic effects in these patients. These findings were published on September 25 in The Lancet Oncology.

“Pegilodecakin with anti-PD-1 monoclonal antibodies had a manageable toxicity profile and promising anti-tumor activity,” explained Aung Naing, MD, associate professor of Investigational Cancer Therapeutics. “Our study showed this combination demonstrated favorable response in NSCLC and kidney cancer patients who previously had been treated when compared to those treated with anti-PD-1 monoclonal antibodies alone.”

Pegilodecakin’s safety, tolerability, and maximal tolerated dose when used with pembrolizumab or nivolumab were of primary interest in this study. The team also aimed to analyze biomarkers to determine how likely the treatment regimen is to invoke a therapeutic response.

Data used in this study was collected from February 2015 to September 2017, including information from 111 kidney cancer, NSCLC and melanoma patients with aggressive tumors. The most prevalent side effects observed in this trial were fatigue, anemia, high triglyceride levels, and low blood platelet counts.

Adequate immune responses were observed in 43% of the NSCLC patients, 40% of those with kidney cancer, and 10% of the melanoma patients. These participants received the pegilodecakin with pembrolizumab or nivolumab either until the study ended, the disease progressed, the onset of detrimental toxicity, or patient withdrawal. These patients continued receiving their combination therapy or pegilodecakin alone after the disease progressed only if the researchers felt that this would continue to have a therapeutic benefit.

How Does Pegilodecakin Work

Pegilodecakin is a treatment containing recombinant interleukin-10 (IL-10) that is connected to polyethylene glycol (PEG). The IL-10 protein is an anti-inflammatory cytokine that can elicit an immune response against malignant cells. The coupling of these two molecules increases the size of the therapeutic complex, allowing the breakdown of IL-10 to be delayed/prevented in the body. By enabling this molecule to circulate throughout the body for a longer time, this combination prolongs the interleukin’s therapeutic effect.

The experimental drug functions by promoting the survival, replication, and anti-cancer properties of CD8+ T cells, which can recognize and kill malignant cells. Increasing the quantity and activity of these CD8+ T cells in the tumor is thought to improve the patient’s symptoms and chances of survival. Pegilodecakin’s effects on the immune system work alongside those of the anti-PD-1 monoclonal antibodies that inhibit immunosuppressive effects on T cells.

“The activity of pegilodecakin in combination with anti-PD-1 monoclonal antibodies introduces a new class of drugs to the treatment of advanced solid tumors. Future randomized trials hopefully will determine the tolerability and clinical benefits of pegilodecakin as a single agent and in combinations in a range of cancers,” concluded Naing.