High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial
van Dorp, Jeroen; Pipinikas, Christodoulos; Suelmann, Britt B.M.; Mehra, Niven; van Dijk, Nick; Marsico, Giovanni; van Montfoort, Maurits L.; Hackinger, Sophie; Braaf, Linde M.; Amarante, Tauanne; van Steenis, Charlaine; McLay, Kirsten; Daletzakis, Antonios; van den Broek, Daan; van de Kamp, Maaike W.; Hendricksen, Kees; de Feijter, Jeantine M.; Boellaard, Thierry N.; Meijer, Richard P.; van der Heijden, Toine G.; Rosenfeld, Nitzan; van Rhijn, Bas W.G.; Jones, Greg; van der Heijden, Michiel S.
(2023) Nature Medicine, volume 29, issue 3, pp. 588 - 592
(Article)
Abstract
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
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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.
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Keywords: General Biochemistry,Genetics and Molecular Biology
ISSN: 1078-8956
Publisher: Nature Publishing Group
Note: Funding Information: We would like to thank all patients and their families who participated in the NABUCCO trial; all staff involved in the care of patients participating in this trial in the Netherlands Cancer Institute; the University Medical Center Utrecht; and the Radboud University Medical Center. We thank the clinical trial teams at participating centers and all staff involved in the collection, processing and storage of trial samples and tumor material. We thank A. Gil-Jimenez for processing the DNA sequencing data and C. Blank for input on the trial design. We thank Bristol Myers Squibb for funding the trial (CA209-9Y4) and for providing the study drugs. The KWF Dutch Cancer Society provided institutional funding. Funding Information: We would like to thank all patients and their families who participated in the NABUCCO trial; all staff involved in the care of patients participating in this trial in the Netherlands Cancer Institute; the University Medical Center Utrecht; and the Radboud University Medical Center. We thank the clinical trial teams at participating centers and all staff involved in the collection, processing and storage of trial samples and tumor material. We thank A. Gil-Jimenez for processing the DNA sequencing data and C. Blank for input on the trial design. We thank Bristol Myers Squibb for funding the trial (CA209-9Y4) and for providing the study drugs. The KWF Dutch Cancer Society provided institutional funding. Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
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