High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial

Jeroen van Dorp, Christodoulos Pipinikas, Britt B. M. Suelmann, Niven Mehra, Nick van Dijk, Giovanni Marsico, Maurits L. van Montfoort, Sophie Hackinger, Linde M. Braaf, Tauanne Amarante, Charlaine van Steenis, Kirsten McLay, Antonios Daletzakis, Daan van den Broek, Maaike W. van de Kamp, Kees Hendricksen, Jeantine M. de Feijter, Thierry N. Boellaard, Richard P. Meijer, Toine G. van der HeijdenNitzan Rosenfeld, Bas W. G. van Rhijn, Greg Jones, Michiel S. van der Heijden

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Cohort 1 of the phase 1B NABUCCO trial showed high pathological complete response (pCR) rates with preoperative ipilimumab plus nivolumab in stage III urothelial cancer (UC). In cohort 2, the aim was dose adjustment to optimize responses. Additionally, we report secondary endpoints, including efficacy and tolerability, in cohort 2 and the association of presurgical absence of circulating tumor DNA (ctDNA) in urine and plasma with clinical outcome in both cohorts. Thirty patients received two cycles of either ipilimumab 3 mg kg−1 plus nivolumab 1 mg kg−1 (cohort 2A) or ipilimumab 1 mg kg−1 plus nivolumab 3 mg kg−1 (cohort 2B), both followed by nivolumab 3 mg kg−1. We observed a pCR in six (43%) patients in cohort 2A and a pCR in one (7%) patient in cohort 2B. Absence of urinary ctDNA correlated with pCR in the bladder (ypT0Nx) but not with progression-free survival (PFS). Absence of plasma ctDNA correlated with pCR (odds ratio: 45.0; 95% confidence interval (CI): 4.9–416.5) and PFS (hazard ratio: 10.4; 95% CI: 2.9–37.5). Our data suggest that high-dose ipilimumab plus nivolumab is required in stage III UC and that absence of ctDNA in plasma can predict PFS. ClinicalTrials.gov registration: NCT03387761.
Original languageEnglish
Pages (from-to)588-592
Number of pages5
JournalNature medicine
Issue number3
Early online date2023
Publication statusPublished - Mar 2023

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