TY - JOUR
T1 - High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer
T2 - the phase 1B NABUCCO trial
AU - van Dorp, Jeroen
AU - Pipinikas, Christodoulos
AU - Suelmann, Britt B.M.
AU - Mehra, Niven
AU - van Dijk, Nick
AU - Marsico, Giovanni
AU - van Montfoort, Maurits L.
AU - Hackinger, Sophie
AU - Braaf, Linde M.
AU - Amarante, Tauanne
AU - van Steenis, Charlaine
AU - McLay, Kirsten
AU - Daletzakis, Antonios
AU - van den Broek, Daan
AU - van de Kamp, Maaike W.
AU - Hendricksen, Kees
AU - de Feijter, Jeantine M.
AU - Boellaard, Thierry N.
AU - Meijer, Richard P.
AU - van der Heijden, Toine G.
AU - Rosenfeld, Nitzan
AU - van Rhijn, Bas W.G.
AU - Jones, Greg
AU - van der Heijden, Michiel S.
N1 - 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.
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85147268572&partnerID=8YFLogxK
U2 - 10.1038/s41591-022-02199-y
DO - 10.1038/s41591-022-02199-y
M3 - Article
AN - SCOPUS:85147268572
SN - 1078-8956
VL - 29
SP - 588
EP - 592
JO - Nature Medicine
JF - Nature Medicine
IS - 3
ER -