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 Pereira; Gaëlle Quéreux; Shahneen Sandhu; Brendan 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; Céleste Lebbé

doi:10.1038/s41698-024-00641-7

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 Pereira, Gaëlle Quéreux, Shahneen Sandhu, Brendan 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. LongCéleste Lebbé

Melanoma Medical Oncology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	150
Journal	npj Precision Oncology
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41698-024-00641-7
State	Published - Dec 2024

ASJC Scopus subject areas

Oncology
Cancer Research

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Gogas, H., Ravimohan, S., Datta, A., Chhibber, A., Couselo, E. M., Diab, A., Pereira, C., Quéreux, G., Sandhu, S., Curti, B., Khushalani, N. I., Taylor, M. H., Daniels, G. A., Spreafico, A., Meniawy, T., Van Den Eertwegh, A. J. M., Sun, Y., Arriaga, Y., Zhou, M., ... Lebbé, C. (2024). Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab. npj Precision Oncology, 8(1), Article 150. https://doi.org/10.1038/s41698-024-00641-7

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 2024, 'Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab', npj Precision Oncology, vol. 8, no. 1, 150. https://doi.org/10.1038/s41698-024-00641-7

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

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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AU - Gogas, Helen

AU - Ravimohan, Shruthi

AU - Datta, Antara

AU - Chhibber, Aparna

AU - Couselo, Eva Muñoz

AU - Diab, Adi

AU - Pereira, Caio

AU - Quéreux, Gaëlle

AU - Sandhu, Shahneen

AU - Curti, Brendan

AU - Khushalani, Nikhil I.

AU - Taylor, Matthew H.

AU - Daniels, Gregory A.

AU - Spreafico, Anna

AU - Meniawy, Tarek

AU - Van Den Eertwegh, Alfons J.M.

AU - Sun, Yongliang

AU - Arriaga, Yull

AU - Zhou, Ming

AU - Long, Georgina V.

AU - Lebbé, Céleste

PY - 2024/12

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N2 - 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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Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab

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