PD-L1 Inhibition Plus Pegilodecakin Active in Advanced Solid Tumor All-Comers

A combination of pegilodecakin (pegylated IL-10) with an anti-PD-L1 monoclonal antibody inhibitor showed preliminary antitumor activity among patients with renal cell carcinoma (RCC) and non–small cell lung cancer (NSCLC), according to the results of  a phase 1b trial. The results were published in Lancet Oncology.

“Pegilodecakin has single-agent activity in patients with advanced solid tumors, and pegilodecakin monotherapy or in combination with anti-PD-1 leads to reinvigoration, proliferation, and expansion of antigen experienced PD-1+ Lag-3+ CD8+ cytotoxic T cells and expansion of novel CD8+ T-cell clones,” wrote Aung Naing, MD, of the University of Texas MD Anderson Cancer Center, and colleagues.

The multicenter study enrolled 111 patients with advanced malignant solid tumors refractory to previous therapy. Patients self-administered pegilodecakin at home and received either pembrolizumab (Keytruda) (n=53) or nivolumab (Opdivo) (n=58) at the study site. The primary endpoints were safety and tolerability. 

In the trial 31% of patients had NSCLC, 33% had melanoma, and 34% had RCC. One patient had triple-negative breast cancer and one had bladder cancer. The median follow-up was 26.9 months for NSCLC, 33.0 months for melanoma, and 22.7 months for RCC. 

Among the patients evaluable for response, 43% of patients with NSCLC and 40% of patients with RCC responded to treatment. Only 10% of patients with melanoma responded. One patient achieved complete response. 

Among patients with NSCLC, 83% of those with at least 50% PD-L1 expression had an objective response. PD-L1 expression had no significant correlation with objective response for RCC. 

The majority of patients (93%) experienced at least one treatment-related adverse event, with grade 3 or 4 events occurring in 66% of patients. The most common grade 3/4 adverse events were anemia, thrombocytopenia, fatigue, and hypertriglyceridemia. No fatal treatment-related adverse events occurred.

In an accompanying editorial, Sumanta Pal, of City of Hope Comprehensive Cancer Center, and colleagues, applauded the strong biological rationale for the combination of the treatments studied, and wrote that differences in prior therapies could account for the differences in response seen between NSCLC and RCC compared with melanoma.

“The investigators concluded that these results did not support further exploration in patients with melanoma; however, these data could simply imply that the addition of pegylated IL-10 might not overcome checkpoint inhibitor resistance in this setting,” they wrote. “The key next step for further development of this combination, and all combination strategies designed to improve the efficacy of checkpoint inhibitors, is to fully understand the mechanisms of response of each combination and develop biomarkers to select patients who would most likely respond.” 

References:

Heng DY, Xie W, Regan MM, et al. "Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study." J Clin Oncol. 2009; 27: 5794-5799