Researchers reported evidence from a phase Ib clinical trial (abstract 4509) that showed that the experimental immunotherapy pegilodecakin is safe and exhibits promising clinical activity in patients with metastatic renal cell carcinoma (mRCC) at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.
Pegilodecakin plus anti–programmed death 1 (PD-1) immune checkpoint blockade was well tolerated in patients with RCC, reported Nizar M. Tannir, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“The preliminary clinical responses and the observed immune activation are encouraging and warrant further exploration of this combination in phase II and III studies in RCC,” Tannir reported.
Pegilodecakin (AM0010) is a long-acting form of interleukin-10 linked to polyethylene glycol (PEGylated IL-10). IL-10 regulates the behavior of immune cells, activating tumor antigen–specific CD8+ T cells and inhibiting their apoptosis, while pegylation increases the molecule’s size to prolong its circulation.
“IL-10 receptors and PD-1 are expressed on activated and exhausted CD8+ T cells,” explained Tannir. “IL-10 stimulates the cytotoxicity and proliferation of CD8+ T cells. This provides a rationale for combining pegilodecakin with anti–PD-1.”
Tannir and colleagues conducted a dose-escalation and clinical activity study to test the safety and tolerability of pegilodecakin in combination with anti–PD-1 immune checkpoint inhibitors, and pegilodecakin alone. Eligible patients had mRCC that progressed on antiangiogenic therapy but no history of Guillain-Barré syndrome or neuroinflammatory disease.
The research team enrolled 19 patients for treatment with pegilodecakin monotherapy (20 μg/kg), of whom 16 were ultimately evaluable. They then enrolled 38 patients in the phase Ib component of the trial, in which patients received one of two doses of pegilodecakin (10 or 20 μg/kg; n = 6 and n = 32, respectively), plus nivolumab (3 mg/kg intravenously every 2 weeks; n = 29) or pembrolizumab (2 mg/kg IV every 3 weeks; n = 9).
The recommended pegilodecakin dose for phase II and III study was 10 μg/kg in combination with an anti–PD-1 immune checkpoint blockade.
“AM0010, with or without anti–PD-1, induces invigoration of CD8+ T cells,” Tannir reported.
Fewer autoimmune-like treatment-related adverse events were seen among patients receiving both pegilodecakin and immune checkpoint blockade.
Patients in the pegilodecakin monotherapy group experienced an objective response rate (ORR) of 25% and had a 1-year overall survival (OS) rate of 47%, compared with an ORR of 41% and a 1-year OS rate of 89% for patients who also underwent immune checkpoint blockade.
In addition to combinations with immune checkpoint inhibitors, pegilodecakin is being studied in combination with chemotherapy.