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

Helen Gogas; Shruthi Ravimohan; Antara Datta; Aparna Chhibber; Eva Muñoz‐Couselo; Adi Diab; Caio Guilherme Pereira; G. Quéreux; Shahneen Sandhu; Brendan D. Curti; Nikhil I. Khushalani; Matthew H. Taylor; Gregory A. Daniels; Anna Spreafico; Tarek Meniawy; Alfons J.M. van den Eertwegh; Yongliang Sun; Yull Arriaga; Ming Zhou; Georgina V. Long; Célèste Lebbé

doi:10.1038/s41698-024-00641-7

Abstract

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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.

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