Rationale for Combining a Modified IL-2 and Nivolumab in Melanoma

Source: Targeted Oncology, July 2019

Nikhil I. Khushalani, MD, vice chair, Department of Cutaneous Oncology, Moffitt Cancer Center, discusses the rationale for combining nivolumab (Opdivo) with bempegaldesleukin (NKTR-214) for the treatment of patients with newly diagnosed, unresectable or metastatic melanoma in a randomized, open-label phase III trial.

Bempegaldesleukin is essentially a pegylated version of interleukin (IL)-2. High-dose IL-2 has been around for over 20 years and has been approved by the FDA for the treatment of advanced melanoma. However, this treatment is limited by its toxicity profile, says Khushalani.

The response rates for this patient population to IL-2 have typically been around 15%, but patients who achieved a complete response maintained their response for a long period of time. As a modified IL-2, bempegaldesleukin causes signaling in the intermediate-affinity IL-2 beta-gamma receptor. This results in an increase in CD8-positive lymphocytes on both T and natural killer (NK) cells within the tumor microenvironment.