A study published in The Lancet Oncology found that pegilodecakin in combination with anti-PD-1 monoclonal antibody inhibitors may be a safe and effective option for patients with advanced solid tumors.
“IL-10 has anti-inflammatory and CD8+ T-cell stimulating activities. Pegilodecakin (pegylated IL-10) is a first-in-class, long-acting IL-10 receptor agonist that induces oligoclonal T-cell expansion and has single-agent activity in advanced solid tumours,” the researchers explained.
The open-label phase 1B trial spanned 12 cancer research centers in the U.S. Patients were aged 18 years or older and had histologically or cytologically confirmed advanced malignant solid tumors refractory to prior therapies and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were excluded if they had an uncontrolled infectious disease.
Eligible patients received pegilodecakin to be administered at home 10 μg/kg or 20 μg/kg once per day in combination with pembrolizumab (2 mg/kg every 3 weeks or 200 mg every 3 weeks) or nivolumab (3 mg/kg every 2 weeks or 240 mg every 2 weeks or 480 mg every 4 weeks at the approved dosing); the add-on drugs were administered intravenously at the study site until disease progression, toxicity warranting treatment cessation, patient withdrawal of consent, or the end of the trial. The primary outcomes were safety and tolerability, and the secondary outcomes included objective response as measured by immune-related response criteria. The researchers noted that the study is still ongoing but new patients are not being accepted.
Of 111 patients enrolled from Feb. 13, 2015, and Sept. 12, 2017, 58 received pegilodecakin plus nivolumab, and 53 received pegilodecakin plus pembrolizumab. Disease prevalence was 31% non-small-cell lung cancer (NSCLC, n = 34), 33% melanoma (n = 37), and 34% renal cell carcinoma (n = 38). One patient had triple-negative breast cancer, and one patient had bladder cancer. Median follow-up times were 26.9 months for NSCLC patients, 33 months for melanoma patients, and 22.7 months for renal cell carcinoma patients. Most patients (n = 111, 93%) experienced at least one treatment-related adverse events; 66% (n = 73) experienced a grade 3 or grade 4 adverse event: 66% (n = 35) in the pembrolizumab group and 66% (n = 38) in the nivolumab group. The most prevalent adverse events were anemia (12 [23%] in the pembrolizumab group and 16 [28%] in the nivolumab group), thrombocytopenia (14 [26%] in the pembrolizumab group and 12 [21%] in the nivolumab group), fatigue (11 [21%] in the pembrolizumab group and 6 [10%] in the nivolumab group) and hypertriglyceridemia (three [6%] in the pembrolizumab group and eight [14%] in the nivolumab group). No treatment-related fatalities occurred.
“Of the patients evaluable for response, objective responses were 12 (43%) of 28 (non-small-cell lung cancer), three (10%) of 31 (melanoma), and 14 (40%) of 35 (renal cell carcinoma),” the authors added.
The researchers posited that the combination therapies “had a manageable toxicity profile and preliminary antitumour activity. Pegilodecakin with pembrolizumab or nivolumab could provide a new therapeutic opportunity for previously treated patients with renal cell carcinoma and non-small-cell carcinoma.”