Randomized Phase-II Study of Nivolumab Plus Ipilimumab vs. Standard of Care in Untreated and Advanced Non-clear Cell RCC

Summary

SUNNIFORECAST (Standard of Care vs. Nivolumab + Ipilimumab as First line treatment of renal cell cancer of non-clear cell subtypes) is a Phase II, randomized, open-label investigator initiated trial (IIT) of Nivolumab (BMS-936558) combined with Ipilimumab vs standard of care in subjects with previously untreated and advanced (unresectable or metastatic) non-clear cell renal cell carcinoma (nccRCC).

Timeline

Start

2017-11-01

Primary completion

2023-11-23

Completion

2023-11-23

Outcome

Met primary endpoint

paper 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). PMID 40180121 ↗

Publications

• Background Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P; CheckMate 025 Investigators. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1803-13. doi: 10.1056/NEJMoa1510665. Epub 2015 Sep 25.
• Background Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, Garcia JA, Vaishampayan UN, Picus J, Hawkins RE, Hainsworth JD, Kollmannsberger CK, Logan TF, Puzanov I, Pickering LM, Ryan CW, Protheroe A, Lusk CM, Oberg S, George DJ. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol. 2016 Mar;17(3):378-388. doi: 10.1016/S1470-2045(15)00515-X. Epub 2016 Jan 13.
• Background Vera-Badillo FE, Templeton AJ, Duran I, Ocana A, de Gouveia P, Aneja P, Knox JJ, Tannock IF, Escudier B, Amir E. Systemic therapy for non-clear cell renal cell carcinomas: a systematic review and meta-analysis. Eur Urol. 2015 Apr;67(4):740-9. doi: 10.1016/j.eururo.2014.05.010. Epub 2014 Jun 2.
• Background Ahrens M, Scheich S, Hartmann A, Bergmann L; IAG-N Interdisciplinary Working Group Kidney Cancer of the German Cancer Society. Non-Clear Cell Renal Cell Carcinoma - Pathology and Treatment Options. Oncol Res Treat. 2019;42(3):128-135. doi: 10.1159/000495366. Epub 2019 Feb 23.
• Background Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.
• Results Bergmann L, Albiges L, Ahrens M, Gross-Goupil M, Boleti E, Gravis G, Flechon A, Grimm MO, Bedke J, Barthelemy P, Castellano D, Mellado B, Ivanyi P, Rottey S, Florcken A, Suarez C, Maroto P, Grunwald V, Oosting SF, Kopecky J, Zschabitz S, Boegemann M, Buchler T, Niegisch G, Goebell PJ, Waddell T, Joly F, Priou F, Retz M, Siemer S, Zimmermann U, Deckbar D, Burkholder I, Hartmann A, Haanen JB; Interdisciplinary Renal Cell Carcinoma Working Group of the DKG (IAGN). Prospective randomized phase-II trial of ipilimumab/nivolumab versus standard of care in non-clear cell renal cell cancer - results of the SUNNIFORECAST trial. Ann Oncol. 2025 Jul;36(7):796-806. doi: 10.1016/j.annonc.2025.03.016. Epub 2025 Apr 1.
• Ahrens M, Haanen J, Albiges L, Goupil MG, Boleti E, Gravis G, Flechon A, Grimm MO, Bedke J, Barthelemy P, Castellano D, Mellado B, Ivanyi P, Rottey S, Florcken A, Suarez C, Maroto JP, Grunwald V, Oosting S, Kopecky J, Zschabitz S, Boegemann M, Buchler T, Niegisch G, Goebell PJ, Waddell T, Joly F, Priou F, Retz M, Siemer S, Zimmermann U, Deckbar D, Burkholder I, Hartmann A, Bergmann L; Interdisciplinary Renal Cell Carcinoma Working Group of the DKG (IAGN). Papillary renal cell carcinoma - exploratory results of the SUNNIFORECAST trial comparing Ipilimumab plus Nivolumab vs standard of care as first line therapy based on central pathological review. Eur J Cancer. 2026 May 27;243:116816. doi: 10.1016/j.ejca.2026.116816. Online ahead of print.

Drugs

Indications