Pegilodecakin Shows Positive Results in Patients with NSCLC, Kidney Cancer

A first-in-class drug currently in clinical trials, pegilodecakin, has shown positive safety results and may offer a potential new treatment approach for patients with non-small cell lung cancer (NSCLC) and kidney cancer, according to a new study by the University of Texas MD Anderson Cancer Center.

The study, published in The Lancet Oncology, demonstrated that pegilodecakin in combination with 2 leading anti-PD-1 monoclonal antibodies, pembrolizumab and nivolumab, achieved measurable responses in patients with NSCLC and kidney cancer. The study was designed to assess the safety, tolerability, and maximal tolerated dose of pegilodecakin in combination with pembrolizumab or nivolumab, while also investigating biomarkers to identify patients likely to respond to treatment.

Researchers followed 111 patients with kidney cancer, NSCLC, and melanoma with advanced malignant solid tumors from 2015 to 2017. Patients received pegilodecakin with pembrolizumab or nivolumab until disease progression, toxicity necessitating treatment discontinuation, patient withdrawal of consent, or study end.

Objective responses were seen in 43% of patients with NSCLC, 40% of patients with kidney cancer, and 10% of patients with melanoma. The most common adverse events were anemia, fatigue, low blood platelet count, and high triglycerides.

Pegilodecakin is comprised of recombinant interleukin-10 (IL-10), a protein that regulates the activity of various immune cells. High concentrations of IL-10 activate an immune response against cancer cells. IL-10 is linked to polyethylene glycol (PEG), which increases its size and prevents or delays breakdown to prolong the time it circulates in the body.

The drug works by stimulating the survival, proliferation, and killing potential of CD8+ T cells, which are known for their ability to recognize and destroy cancer cells. Increasing the amount of CD8+ T cells within the tumor is thought to improve the prognosis and survival of the patient. The immune stimulatory effect of pegilodecakin complements the action of anti-PD-1 monoclonal antibodies that blocks the immune suppressive effect on T cells, according to the study.

The authors note that future randomized trials may determine the tolerability and clinical benefits of pegilodecakin as a single agent and in combinations across a range of cancers.

Reference

• Naing A, Wong D, Infante J, et al. Pegilodecakin combined with pembrolizumab or nivolumab for patients with advanced solid tumours (IVY): a multicentre, multicohort, open-label, phase 1b trial. The Lancet Oncology, 2019 DOI: 10.1016/S1470-2045(19)30514-5