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

NPJ Precis Oncol. 2024 Jul 19;8(1):150. doi: 10.1038/s41698-024-00641-7.

Authors

Helen Gogas¹, Shruthi Ravimohan², Antara Datta², Aparna Chhibber², Eva Muñoz Couselo³, Adi Diab⁴, Caio Pereira⁵, Gaëlle Quéreux⁶, Shahneen Sandhu⁷, Brendan Curti⁸, Nikhil I Khushalani⁹, Matthew H Taylor⁸, Gregory A Daniels¹⁰, Anna Spreafico¹¹, Tarek Meniawy¹², Alfons J M Van Den Eertwegh¹³, Yongliang Sun², Yull Arriaga², Ming Zhou², Georgina V Long¹⁴, Céleste Lebbé^{15

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Affiliations

¹ National and Kapodistrian University of Athens, Athens, Greece. helgogas@gmail.com.
² Bristol Myers Squibb, Princeton, NJ, USA.
³ Vall d'Hebron Barcelona Hospital and Vall d'Hebron Instituto de Oncología (VHIO), Barcelona, Spain.
⁴ MD Anderson Cancer Center, Houston, TX, USA.
⁵ Fundação Pio XII - Hospital de Câncer de Barretos, São Paulo, Brazil.
⁶ Unité Cancéro-Dermatologie, Nantes, France.
⁷ Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
⁸ Eerle A. Chiles Research Institute, Providence Cancer Institute of Oregon, Portland, OR, USA.
⁹ Moffitt Cancer Center, Tampa, FL, USA.
¹⁰ Moores UCSD Cancer Center, La Jolla, CA, USA.
¹¹ Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
¹² Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia.
¹³ Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands.
¹⁴ The Melanoma Institute Australia, The University of Sydney and Royal North Shore and Mater Hospitals, Sydney, NSW, Australia.
¹⁵ Université Paris Cité, Dermato-Oncology and CIC AP-HP Hôpital Saint Louis, Cancer Institute APHP, Nord-Université Paris Cité, Paris, France.
¹⁶ INSERM U976 HIPI, Paris, France.

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.

Abstract

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