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EV-302

Enfortumab vedotin and pembrolizumab versus gemcitabine plus cisplatin or carboplatin in previously untreated locally advanced or metastatic urothelial carcinoma

Phase 3N = 886NCT04223856

Population
Adults with previously untreated locally advanced or metastatic urothelial carcinoma
Design
Global, open-label, randomised phase 3 trial; 1:1 to enfortumab vedotin 1.25 mg/kg (days 1 and 8) plus pembrolizumab 200 mg (day 1) in 3-week cycles, or gemcitabine plus either cisplatin or carboplatin (chosen by cisplatin eligibility). Dual primary endpoints: progression-free survival by blinded independent central review, and overall survival.
Primary endpoint
PFS, OS
Arms
  • Enfortumab vedotin plus pembrolizumab (experimental, n = 442): Enfortumab vedotin 1.25 mg/kg IV days 1 and 8 plus pembrolizumab 200 mg IV day 1 of 3-week cycles
  • Platinum-based chemotherapy (control, n = 444): Gemcitabine plus either cisplatin or carboplatin (by cisplatin eligibility), 3-week cycles
People
Powles T, EV-302 Trial Investigators
PFSHR 0.45 (95% CI 0.38–0.54)Δ median PFS+6.2 monthsOSHR 0.47 (95% CI 0.38–0.58)Δ median OS+15.4 monthsPFSHR 0.48 (95% CI 0.41–0.57)Δ median PFS+6.2 months
Show the numbers
Results reported for EV-302
EndpointAnalysisEnfortumab vedotin plus pembrolizumabPlatinum-based chemotherapyEffect
PFSAll randomised patients (n = 886)Progression-free survival assessed by blinded independent central reviewprimarymedian follow-up 17.2 monthsPowles 2024median 12.5 monthsmedian 6.3 monthsHR 0.45 (95% CI 0.38–0.54)P<0.001Median follow-up of 17.2 months is the duration of follow-up for survival as stated in the abstract.
OSAll randomised patients (n = 886)primarymedian follow-up 17.2 monthsPowles 2024median 31.5 monthsmedian 16.1 monthsHR 0.47 (95% CI 0.38–0.58)P<0.001
PFSOverall populationProgression-free survival by blinded independent central reviewlong term-updatemedian follow-up 2.5 yearsPowles 2025median 12.5 months (10.4–16.6)median 6.3 months (6.2–6.5)HR 0.48 (95% CI 0.41–0.57)
OSOverall populationlong term-updatemedian follow-up 2.5 yearsPowles 2025median 33.8 months (26.1–39.3)median 15.9 months (13.6–18.3)HR 0.51 (95% CI 0.43–0.61)
Results reported for EV-302
EndpointAnalysisEnfortumab vedotin plus pembrolizumabPlatinum-based chemotherapyEffect
PFSAll randomised patients (n = 886)Progression-free survival assessed by blinded independent central reviewprimarymedian follow-up 17.2 monthsPowles 2024median 12.5 monthsmedian 6.3 monthsHR 0.45 (95% CI 0.38–0.54)P<0.001Median follow-up of 17.2 months is the duration of follow-up for survival as stated in the abstract.
OSAll randomised patients (n = 886)primarymedian follow-up 17.2 monthsPowles 2024median 31.5 monthsmedian 16.1 monthsHR 0.47 (95% CI 0.38–0.58)P<0.001
PFSOverall populationProgression-free survival by blinded independent central reviewlong term-updatemedian follow-up 2.5 yearsPowles 2025median 12.5 months (10.4–16.6)median 6.3 months (6.2–6.5)HR 0.48 (95% CI 0.41–0.57)
OSOverall populationlong term-updatemedian follow-up 2.5 yearsPowles 2025median 33.8 months (26.1–39.3)median 15.9 months (13.6–18.3)HR 0.51 (95% CI 0.43–0.61)
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOSPFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.450.38–0.54
OS0.470.38–0.58
PFS0.480.41–0.57
OS0.510.43–0.61
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%051015202530Months (modelled)
  • Enfortumab vedotin plus pembrolizumab (experimental)
  • Platinum-based chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsEnfortumab vedotin plus pembrolizumabPlatinum-based chemotherapy
0100.0%100.0%
864.2%41.5%
1641.2%17.2%
2327.9%8.0%
3117.9%3.3%
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%0204060Months (modelled)
  • Enfortumab vedotin plus pembrolizumab (experimental)
  • Platinum-based chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsEnfortumab vedotin plus pembrolizumabPlatinum-based chemotherapy
0100.0%100.0%
2064.4%42.3%
3942.4%18.7%
5927.3%7.9%
7917.6%3.3%
Primary publication: Powles T, Valderrama BP, Gupta S, Bedke J, Kikuchi E, Hoffman-Censits J, et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med. 2024;390(10):875-888. PubMedDOI

Appears in

Sources

  1. Powles T, Valderrama BP, Gupta S, Bedke J, Kikuchi E, Hoffman-Censits J, et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med. 2024;390(10):875-888.

    PubMedDOI

  2. Powles TB, Van der Heijden MS, Loriot Y, Bedke J, Valderrama BP, Iyer G, et al. Enfortumab vedotin plus pembrolizumab in untreated locally advanced or metastatic urothelial carcinoma: 2.5-year median follow-up of the phase III EV-302/KEYNOTE-A39 trial. Ann Oncol. 2025;36(10):1212-1219.

    PubMedDOI