Comparison between phase III front-line UC trials

TrialExperimental arm vs. standard armPrimary endpointSecondary endpointsToxicityUS FDA approval
JAVELIN Bladder 100 [19]Gem/cis or carbo followed by avelumab + BSC vs. BSCUpdated mOS: 23.8 mos (Ave) vs. 15 mos (BSC); OS at 1 year: 71.3% (Ave) vs. 58.4% (BSC)mPFS: 5.5 mos (Ave) vs. 2.1 mos (BSC); updated 2-year PFS: 23.4% (Ave) vs. 7.1% (BSC); trAE: 98.3% pts (Ave group) vs. 77.0% pts (BSC); at eligibility: CR 25.7%; PR = 46.6%; SD = 27.7%Grade >/= 3: Ave (47.4%) vs. BSC (77.7%); Ave included: UTI (4.4%), anemia (3.8%), hematuria (1.7%), fatigue (1.7%), back pain (1.2%), vomiting (1.2%)June 30, 2020: Ave maintenance treatment of pts with la or mUC that has not progressed with first-line platinum-containing chemotherapy
EV-302 [15]EV+P vs. gem/cis or carbomOS: 31.5 mos (EV+P group) vs. 16.1 mos (chemotherapy group); PFS: 12.5 mos (EV+P group) vs. 6.3 mos (chemotherapy group)ORR: 67.7% (CR = 29.1%) in the EV+P vs. 44.4% (CR = 12.5%) in the chemotherapy group; TTP: 14.2 mos (EV+P group) vs. 10.0 mos (chemotherapy group)Grade >/= 3 trAE: 55.9% with EV+P vs. 69.5% with chemotherapy; EV+P grade >/= 3 included: rash (7.7%), hyperglycemia (5.0%), neutropenia (4.8%)December 15, 2023: EV+P for pts with locally advanced or mUC
CheckMate 901 (sub-study) [16]Gem/cis + nivo vs. gem/cismOS: 21.7 mos (GC + nivo) vs. 18.9 mos (gem/cis); PFS at 12 mos: 34.2% (GC + nivo) vs. 21.8% (gem/cis)ORR: 57.6% (CR = 21.7%) GC + nivo vs. 43.1% (CR = 11.8%) GC; OS and PFS in PD-L1 expression of >/= 1% favored GC + nivo (HR: 0.75, 95% CI: 0.53 to 1.06) over GC group (HR: 0.60, 95% CI: 0.41 to 0.81)Grade >/= 3 AE: 61.8% of gem/cis + nivo group vs. 51.7% in gem/cis group; trAE with gem/cis + nivo were anemia (57.2%), nausea (46.7%), and neutropenia (30.6%)March 6, 2024: GC + nivo for first-line treatment of pts with unresectable or mUC

Ave: avelumab; cis: cisplatin; carbo: carboplatin; gem: gemcitabine; nivo: nivolumab; EV: enfortumab vedotin; EV+P: enfortumab vedotin plus pembrolizumab; BSC: best supportive care; PFS: progression-free survival; OS: overall survival; mOS: median overall survival; mos: months; ORR: objective response rates; TPP: time to pain progression; mUC: metastatic urothelial carcinoma; trAE: treatment-related adverse events; la: locally advanced; AE: adverse events; GC: gemcitabine/cisplatin; UTI: urinary tract infection; TTP: time to progression; HR: hazard ratios; CI: confidence intervals; pts: patients; CR: complete response; SD: stable disease; PR: partial response; PD-L1: programmed death ligand-1