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EV-103

Enfortumab vedotin with or without pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial cancer (EV-103/KEYNOTE-869, cohort K)

Phase 1/2NCT03288545

Population
Cisplatin-ineligible adults with previously untreated locally advanced or metastatic urothelial cancer
Design
Multicohort phase 1b/2 study. In cohort K, cisplatin-ineligible patients were randomised 1:1 to enfortumab vedotin alone or with pembrolizumab; primary endpoint confirmed objective response rate by blinded independent central review; no formal statistical comparison between arms. The FDA summary pools 121 patients across cohorts who received the combination.
Primary endpoint
ORR
Arms
  • Cohort K: enfortumab vedotin plus pembrolizumab (experimental, n = 76): Enfortumab vedotin plus pembrolizumab
  • Cohort K: enfortumab vedotin alone (not formally compared) (control, n = 73): Enfortumab vedotin monotherapy
  • Combination, all cohorts (FDA summary) (experimental, n = 121): Enfortumab vedotin 1.25 mg/kg (maximum 125 mg) IV days 1 and 8 plus pembrolizumab 200 mg IV day 1 of 21-day cycles
People
O'Donnell PH
Δ ORR+19.3 pointsΔ 12-month DOR+9.1 points
Show the numbers
Results reported for EV-103
EndpointAnalysisCohort K: enfortumab vedotin plus pembrolizumab / Combination, all cohorts (FDA summary)Cohort K: enfortumab vedotin alone (not formally compared)Effect
ORRCohort K (combination n = 76; monotherapy n = 73)Confirmed objective response rate by blinded independent central reviewprimaryO'Donnell 202364.5% (52.7–75.1%)45.2% (33.5–57.3%)No formal statistical comparison between arms was performed (Methods, abstract).
DORResponders in cohort KprimaryO'Donnell 202365.4% at 12 momedian 13.2 months; 56.3% at 12 moMedian duration of response was not reached with the combination; the 12-month figures are the percentages of responders maintaining response.
ORR121 patients who received the combination across cohorts (FDA summary)primaryMaguire 202468% (59–76%)—Regulatory review analysis supporting the April 2023 accelerated approval; 12% of patients had a complete response.
DOR82 responders (FDA summary)primaryMaguire 2024median 22 months—Range 1+ to 46+ months.
Results reported for EV-103
EndpointAnalysisCohort K: enfortumab vedotin plus pembrolizumab / Combination, all cohorts (FDA summary)Cohort K: enfortumab vedotin alone (not formally compared)Effect
ORRCohort K (combination n = 76; monotherapy n = 73)Confirmed objective response rate by blinded independent central reviewprimaryO'Donnell 202364.5% (52.7–75.1%)45.2% (33.5–57.3%)No formal statistical comparison between arms was performed (Methods, abstract).
DORResponders in cohort KprimaryO'Donnell 202365.4% at 12 momedian 13.2 months; 56.3% at 12 moMedian duration of response was not reached with the combination; the 12-month figures are the percentages of responders maintaining response.
ORR121 patients who received the combination across cohorts (FDA summary)primaryMaguire 202468% (59–76%)—Regulatory review analysis supporting the April 2023 accelerated approval; 12% of patients had a complete response.
DOR82 responders (FDA summary)primaryMaguire 2024median 22 months—Range 1+ to 46+ months.
Illustrative — modelled from reported values, not trial data. DOR, primary.
0%25%50%75%100%051015202530Months (modelled)
  • Cohort K: enfortumab vedotin alone (not formally compared) (control)

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

Data table (modelled values)
MonthsCohort K: enfortumab vedotin alone (not formally compared)
0100.0%
865.7%
1741.0%
2526.9%
3317.7%
Illustrative — modelled from reported values, not trial data. DOR, primary.
0%25%50%75%100%01020304050Months (modelled)
  • Combination, all cohorts (FDA summary) (experimental)

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

Data table (modelled values)
MonthsCombination, all cohorts (FDA summary)
0100.0%
1464.3%
2841.4%
4127.5%
5517.7%
Primary publication: O'Donnell PH, Milowsky MI, Petrylak DP, Hoimes CJ, Flaig TW, Mar N, et al. Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. J Clin Oncol. 2023;41(25):4107-4117. PubMedDOI

Appears in

Sources

  1. O'Donnell PH, Milowsky MI, Petrylak DP, Hoimes CJ, Flaig TW, Mar N, et al. Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. J Clin Oncol. 2023;41(25):4107-4117.

    PubMedDOI

  2. Maguire WF, Lee D, Weinstock C, Gao X, Bulik CC, Agrawal S, et al. FDA Approval Summary: Enfortumab Vedotin plus Pembrolizumab for Cisplatin-Ineligible Locally Advanced or Metastatic Urothelial Carcinoma. Clin Cancer Res. 2024;30(10):2011-2016.

    PubMedDOI