Enhanced efficacy of ipilimumab plus nivolumab in angiogenic subtypes of metastatic clear-cell renal cell carcinoma

Xiaofan Lu; Yann-Alexandre Vano; Xiaoping Su; Virginie Verkarre; Cheng-Ming Sun; Wenxuan Cheng; Li Xu; Fangrong Yan; Salma Kotti; Wolf Herman Fridman; Catherine Sautes-Fridman; Stéphane Oudard; Gabriel G Malouf

doi:10.1038/s41698-025-00912-x

Enhanced efficacy of ipilimumab plus nivolumab in angiogenic subtypes of metastatic clear-cell renal cell carcinoma

NPJ Precis Oncol. 2025 May 8;9(1):134. doi: 10.1038/s41698-025-00912-x.

Authors

Xiaofan Lu^#¹, Yann-Alexandre Vano^#^{2

3}, Xiaoping Su^#⁴, Virginie Verkarre⁵, Cheng-Ming Sun³, Wenxuan Cheng¹, Li Xu¹, Fangrong Yan⁶, Salma Kotti², Wolf Herman Fridman³, Catherine Sautes-Fridman³, Stéphane Oudard⁷, Gabriel G Malouf^{8

9}

Affiliations

¹ Department of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology, CNRS/INSERM/UNISTRA, 67400, Illkirch, France.
² Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, APHP, Université Paris Cité, Paris, France.
³ Centre de Recherche Cordeliers, INSERM 1138, Université de Paris Cité, Sorbonne Université, Equipe labellisée Ligue contre le Cancer, F-75006, Paris, France.
⁴ Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ Department of Pathology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, APHP, Université Paris Cité, Paris, France.
⁶ Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China.
⁷ Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, APHP, Université Paris Cité, Paris, France. stephane.oudard@aphp.fr.
⁸ Department of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology, CNRS/INSERM/UNISTRA, 67400, Illkirch, France. maloufg@igbmc.fr.
⁹ Department of Medical Oncology, Strasbourg University, Institut de Cancérologie de Strasbourg, Strasbourg, France. maloufg@igbmc.fr.

^# Contributed equally.

Abstract

In metastatic clear-cell renal cell carcinoma (mccRCC), choosing between immuno-oncology (IO) combinations and IO plus anti-VEGF therapies is uncertain. The BIONIKK trial revealed that ipilimumab plus nivolumab (Ipi/Nivo) achieved a 70% objective response rate in angiogenic cluster1/2 versus 41% in cluster4/5, which featured T-effector/cell-cycle signatures (p = 0.048). Complete responses were exclusively observed in cluster1/2 (p = 0.012), with longer progression-free survival (p = 0.014). Ipi/Nivo may particularly benefit angiogenic mccRCC, supporting molecular subtype-based treatment strategies.

Grants and funding

SIGNIT/Fondation ARC