Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab.

Gogas H, Ravimohan S, Datta A, Chhibber A, Couselo EM, Diab A, Pereira C, Quéreux G, Sandhu S, Curti B, Khushalani NI, Taylor MH, Daniels GA, Spreafico A, Meniawy T, Van Den Eertwegh AJM, Sun Y, Arriaga Y, Zhou M, Long GV, Lebbé C. npj Precision Oncology, 8, no. 1, (Jul 19 2024): 150, doi:10.1038/s41698-024-00641-7.

Abstract

In PIVOT IO 001 (NCT03635983), the combination of the investigational interleukin-2 agonist bempegaldesleukin (BEMPEG) with nivolumab (NIVO) had no added clinical benefit over NIVO monotherapy in unresectable/metastatic melanoma. Pre-defined baseline and on-treatment changes in selected biomarkers were analyzed to explore the potential mechanisms underlying the clinical observations. In each treatment arm, higher baseline tumor mutational burden or immune infiltration/inflammation was associated with improved efficacy compared with lower levels. On-treatment peripheral biomarker changes showed that BEMPEG + NIVO increased all immune cell subset counts interrogated, including regulatory T cells. This was followed by attenuation of the increase in CD8 + T cells, conventional CD4 + T cells, and systemic interferon gamma levels at later treatment cycles in the combination arm. Changes in tumor biomarkers were comparable between arms. These biomarker results help provide a better understanding of the mechanism of action of BEMPEG + NIVO and may help contextualize the clinical observations from PIVOT IO 001.