Prospective randomized phase-II trial of ipilimumab/nivolumab versus standard of care in non-clear cell renal cell cancer - results of the SUNNIFORECAST trial

Bergmann L, Albiges L, Ahrens M, Gross-Goupil M, Boleti E, Gravis G, Fléchon A, Grimm MO, Bedke J, Barthélémy P, Castellano D, Mellado B, Ivanyi P, Rottey S, Flörcken A, Suarez C, Maroto P, Grünwald V, Oosting SF, Kopecky J, Zschäbitz S, Boegemann M, Buchler T, Niegisch G, Goebell P, Waddell T, Joly F, Priou F, Retz M, Siemer S, Zimmermann U, Deckbar D, Burkholder I, Hartmann A, Haanen JB (2025)

Publication Type: Journal article

Publication year: 2025

Journal

DOI: 10.1016/j.annonc.2025.03.016

Abstract

Background: Non-clear cell renal cell cancers (nccRCCs) are a heterogeneous group of more than 20 different entities, but are rarely included in large, randomized trials. Tyrosine kinase inhibitors with or without immune checkpoint inhibition are considered as a standard of care (SOC), but optimal treatment is not yet defined. We designed the first prospective randomized trial comparing ipilimumab/nivolumab to SOC. Patients and methods: We randomized adult patients with previously untreated advanced or metastatic nccRCC 1:1 to nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by fixed dose nivolumab of 240 mg every 2 weeks or 480 mg every 4 weeks or to SOC. Patients were stratified by histology and by IMDC risk score. Central pathology review was mandatory. The primary endpoint was the overall survival (OS) rate at 12 months, secondary endpoints included median OS, response rate, progression-free survival (PFS), safety and quality of life. Results: In total, 157 patients were assigned to receive ipilimumab/nivolumab, and 152 to SOC. The 12-month survival rate was 78% with ipilimumab/nivolumab [95% confidence interval (CI) 71-84%] compared to 68% with SOC (95% CI 60-75%, P = 0.026). Median OS was 33.2 months versus 25.2 months, P = 0.163 [HR 0.81 (0.61-1.099)]. PFS was similar in both arms [HR 0.99 (0.77-1.28)]. The ORR was 32.8% versus 19.3%. No major differences between papillary and non-papillary RCC subtypes were observed for any endpoint. Exploratory analysis showed a significant OS advantage [HR 0.56 (95% CI 0.37-0.86)] associated with a PD-L1 CPS score ≥1. Treatment discontinuation due to toxicity occurred in 27 patients (17%) with ipilimumab/nivolumab and 13 patients (9%) with SOC. Conclusions: Ipilimumab/nivolumab demonstrated a significantly longer OS at the 12-month milestone and an acceptable toxicity profile. Our results therefore underline a relevant clinical benefit of ipilimumab/nivolumab in previously untreated nccRCC entities compared to current SOC.

Authors with CRIS profile

Involved external institutions

Royal Free London NHS Foundation Trust / Royal Free Hampstead NHS Trust United Kingdom (GB) Institute Paoli-Calmettes France (FR) Centre Léon-Bérard (UNICANCER) France (FR) Universitätsklinikum Jena Germany (DE) Eberhard Karls Universität Tübingen Germany (DE) Hospital Clínic de Barcelona Spain (ES) Centre Hospitalier Départemental Vendée France (FR) Klinikum rechts der Isar Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) University Hospital Ghent Belgium (BE) Berliner Institut für Gesundheitsforschung (BIH) Germany (DE) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron Spain (ES) Hospital de la Santa Creu i Sant Pau Spain (ES) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Institut Gustave-Roussy France (FR) Centre Hospitalier Universitaire de Bordeaux / CHU Bordeaux France (FR) Universitätsklinikum Essen Germany (DE) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) University Hospital Hradec Králové / Fakultní Nemocnice Hradec Králové Czech Republic (CZ) Universitätsklinikum Heidelberg Germany (DE) Universitätsklinikum Münster Germany (DE) Thomayer University Hospital / Fakultní Thomayerovy nemocnice (FTN) Czech Republic (CZ) Universitätsklinikum Düsseldorf Germany (DE) Christie NHS Foundation Trust United Kingdom (GB) Center François Baclesse / Centre Régional de Lutte contre le Cancer François Baclesse (CRLCC) France (FR) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald Germany (DE) Fachhochschule Münster Germany (DE) Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI / NKI-AVL) Netherlands (NL)

How to cite

APA:

Bergmann, L., Albiges, L., Ahrens, M., Gross-Goupil, M., Boleti, E., Gravis, G.,... Haanen, J.B. (2025). Prospective randomized phase-II trial of ipilimumab/nivolumab versus standard of care in non-clear cell renal cell cancer - results of the SUNNIFORECAST trial. Annals of Oncology. https://doi.org/10.1016/j.annonc.2025.03.016

MLA:

Bergmann, L., et al. "Prospective randomized phase-II trial of ipilimumab/nivolumab versus standard of care in non-clear cell renal cell cancer - results of the SUNNIFORECAST trial." Annals of Oncology (2025).

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