Nivolumab and ipilimumab maintenance therapy for advanced or metastatic urothelial carcinoma: Final results from SOGUG-VEXILLUM trial.

747 Background: The pioneering study was designed when platinum-based chemotherapy was the standard of care for advanced urothelial carcinoma and evaluated whether dual ICI (CTL4-PD1) could improve the benefit of maintenance therapy in this setting. Methods: This unique single-arm, multicentre study included patients with unresectable urothelial cancer that did not progress after first-line platinum-based CT (at least 4-6 cycles). The study treatment consisted of four cycles of ipilimumab (ipi) 3 mg/kg and nivo 1 mg/kg every 3 weeks (Q3W), followed by nivolumab (nivo) maintenance therapy (Q4W). The primary endpoint was progression-free survival (PFS) from the start of maintenance therapy in the overall and PD-L1 positive populations. Sample size was estimated using a Simon II stage design for the 4-months PFS rate (H0= 40%; H1= 60%; α = 0.05; β = 90%), requiring 25 patients in the 1st stage and up to 66 in total. Here, we report the final results of the study, which met the criteria to proceed to the second stage but was prematurely closed following the emergence of a new standard of care (enfortumab vedotin + pembrolizumab) in this setting. Results: From Sep 2022 to Apr 2024, 25 patients were included and received nivolumab and ipilimumab maintenance after first-line CT with gemcitabine combined with cisplatin in 14 patients (56%) or carboplatin in 11 (44%). The median age was 64 years (range: 53-79) and most were male (80%). At data cutoff, the median follow-up was 24 months (95% CI: 7-25.3), the 1- and 2-year PFS rates were 36% (95% CI: 21.4-60.7) and 28% (95% CI: 14.9-52.5), respectively, and the median PFS was 5.6 months (95% CI: 3.2-not reached NR). The median OS was 27.4 months (95% CI: 10.1-NR), with 64% (95% CI: 47.7-85.9) and 60% (95% CI: 43.6-82.6) patients alive at 1- and 2-years from the start of nivo/ipi, respectively. Five patients (20%) completed the scheduled 2 years of treatment. Nivo and ipi were permanently discontinued due to toxicity in 4 patients (16%). Grade ≥3 toxicities were observed in 10 patients (40%), with the most common being elevated ALT/AST (12%), immune-mediated hepatitis (8%), and diarrhea (8%). Conclusions: Despite the limited sample size, dual ICI maintenance with nivo plus ipi achieved durable disease control, with 60% of patients alive at 2 years, numerically exceeding historical outcomes from PD-1/PD-L1 monotherapy. The signal supports further exploration of dual ICI as a potential maintenance strategy in this disease. Comprehensive spatial transcriptomics and microbiome analyses are ongoing and will be presented. Clinical trial information: NCT05219435 .