IBCN 2022: Updated Follow-up Data and Biomarker Analysis of Pre-operative Ipilimumab and Nivolumab in Locoregional Advanced Urothelial Cancer (NABUCCO)

(UroToday.com) Patients (pts) with locoregional advanced urothelial cancer (n=54) were preoperatively treated with ipilimumab (ipi) plus nivolumab (nivo) using different dosing regimens. Pts in cohort 1 and 2A were treated with ipi 3 mg/kg (ipi-high) and pts in cohort 2B were treated with ipi 1 mg/kg (ipi-low). A response, defined as ypT0/Tis/Ta/T1N0 for biomarker purposes, was achieved in 22/38 (58%) pts in the ipi-high cohorts and in 4/14 (29%) pts in the ipi-low cohort. They presented updated follow-up data and an exploratory biomarker analysis to better understand the difference between ipi-low and ipi-high. Using a multiplex PCR-based NGS assay (RaDaR), they aimed to confirm pre-operative plasma ctDNA detection to predict response in cohort 2.

Somatic variants associated with response were investigated using WES on baseline tumor and whole blood DNA. Plasma ctDNA status was evaluated using the RaDaR assay. Baseline PD-L1 was determined by IHC using the 22C3 pharmDx test. Tumor immune cell infiltration was studied using multiplex immunofluorescence.

In an updated survival analysis (cutoff March 2022), PFS at 1yr was numerically better in the ipi-high cohorts (85% in cohort 1 and 75% in cohort 2A) vs ipi-low (55% in cohort 2B; p=0.0880). At this early analysis, especially for cohort 2, OS at 1yr was similar in ipi-high cohorts vs the ipi-low cohort (90% in cohort 1+2A vs 85% in cohort 2B; p=0.7185) The response rate in the ipi-high cohort was 69.6% in the PD-L1 positive group vs 42.9% in the PD-L1 negative group, and 42.8% in the PD-L1 positive group vs 14.3% in the PD-L1 negative group in the ipi-low cohort. A higher TMB was observed in responders compared to non-responders (cohort 1+2A+B; p=0.00099). In cohort 1, plasma ctDNA was undetectable after pre-operative treatment in 13/14 responders and in 4/10 nonresponders (p=0.0088; presented AACR 2022). Confirmation of these observations on cohort 2 are pending.

In summary, pre-operative ipi+nivo in stage III UC, particularly in the ipi-high cohorts, leads to encouraging PFS. PD-L1 does not predict response in ipi-high pts. TMB can potentially evolve as biomarker for response to ipi+nivo in UC. Conclusions of pending assays will be presented at the IBCN meeting.

Presented by: Chantal Stockem, MDPh.D. Candidate, Netherlands Cancer Institute, Amsterdam/NL

 Written by: Stephen B. Williams, MD, MS, FACS, @SWilliams_MD on Twitter, Division of Urology, University of Texas Medical Branch, Galveston, TX; Department of Surgery, University of Texas Medical Branch, Galveston, TX during the International Bladder Cancer Network Annual Meeting, September 28-October 1, 2022, Barcelona, Spain