Perioperative Enfortumab Vedotin (EV) Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Chemotherapy for Cisplatin-Eligible Muscle Invasive Bladder Cancer (MIBC) (MK-3475-B15/ KEYNOTE-B15 / EV-304)

Conditions

• Bladder Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Pembrolizumab — BIOLOGICAL
  200 mg of Pembrolizumab IV infusion, on Day 1 Q3W for 4 cycles (each cycle length = 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 Q3W for 13 cycles in postoperative phase (up to approximately 9 months). The total duration of treatment is up to approximately 1 year.
• Enfortumab vedotin (EV) — BIOLOGICAL
  1.25 mg/kg of EV IV infusion, on Day 1 and Day 8 Q3W for 4 cycles (each cycle length = 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 and Day 8 Q3W for 5 cycles (each cycle length = 21 days) in postoperative phase (up to approximately 4 months). The total duration of treatment is up to approximately 7 months.
• RC + PLND — PROCEDURE
  Curative intent RC + PLND surgery will be administered to all participants randomized to Arm A and B after completion of preoperative systemic treatment (RC + PLND to be done approximately at 15 weeks from randomization).
• Gemcitabine — DRUG
  1000 mg/m\^2 of Gemcitabine IV infusion, Day 1 and Day 8 Q3W for 4 cycles in preoperative phase (up to approximately 3 months)
• Cisplatin — DRUG
  70 mg/m\^2 of Cisplatin IV infusion, Day 1, Q3W for 4 cycles in preoperative phase (up to approximately 3 months)

Study Details

The purpose of this study is to assess the antitumor efficacy and safety of perioperative enfortumab vedotin (EV) plus pembrolizumab and radical cystectomy (RC) + pelvic lymph node dissection (PLND) compared with the current standard of care (neoadjuvant chemotherapy \[gemcitabine plus cisplatin\] and RC + PLND) for participants with MIBC who are cisplatin-eligible. The primary hypothesis is perioperative EV and pembrolizumab and RC + PLND (Arm A) will achieve superior event free survival (EFS) compared with neoadjuvant gemcitabine + cisplatin and RC + PLND (Arm B).

Key Dates

Start date

Apr 21, 2021

Status verified

Feb 2026

Primary completion

Oct 27, 2025

Completion

Oct 27, 2025

Study Design

Enrollment

808 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A: Perioperative EV+ Pembrolizumab and RC + PLND
  Participants receive 4 cycles (each cycle length = 21 days) of EV intravenous (IV) infusion plus pembrolizumab IV infusion preoperatively, followed by RC + PLND, followed by 5 cycles of adjuvant EV IV infusion plus 13 cycles of adjuvant pembrolizumab IV infusion postoperatively. The total treatment duration is up to approximately 1 year.
• Active Comparator: Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND
  Participants receive 4 cycles (each cycle length = 21 days) of standard of care (SOC) chemotherapy (gemcitabine IV infusion plus cisplatin IV infusion) preoperatively, followed by RC + PLND. The total treatment duration is up to approximately 3 months.

Primary Outcome Measure

Event-Free Survival (EFS) [ Time Frame: Up to ~68 months ]

Locations (22)

Related coverage on Hipa.ai

• Pembrolizumab Phase 3 Trial for Bladder Cancer Completes Primary Data Collection
  Pembrolizumab · Oct 27, 2025 · ClinicalTrials.gov

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