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Perioperative Enfortumab Vedotin (EV) + Pembrolizumab vs Neoadjuvant Chemotherapy for Cisplatin-Eligible Muscle-Invasive Bladder Cancer (MIBC)

A phase 3, randomized, open-label study to investigate the antitumor efficacy and safety of perioperative EV + 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

Study Identifier

KEYNOTE-B15 Identifier:


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Study Details

The dual primary hypotheses are preoperative EV + pembrolizumab and RC+PLND (Arm A) will achieve superior pathologic complete response (pCR) rate and 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).

Study Phase


Medical Condition


Intervention Type

Parallel Assignment

Inclusion Criteria
  • Have a histologically confirmed diagnosis of urothelial carcinoma (UC)/muscle-invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology
  • Have clinically non-metastatic bladder cancer (≤N1 M0) determined by imaging
  • Eligible for RC+PLND
  • Eligible for cisplatin
  • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Have adequate organ function
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Exclusion Criteria
  • Has a known additional malignancy that is progressing or has required active anticancer treatment ≤3 years of study randomization with certain exceptions
  • Has received any prior systemic treatment for MIBC or non–muscle-invasive bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
  • Has ≥N2 disease or metastatic disease (M1) as identified by imaging
  • Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder
  • Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC
  • Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
  • Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection, hepatitis B infection, or known active hepatitis C infection
  • Has a known psychiatric or substance abuse disorder
  • Has had an allogeneic tissue/solid organ transplant
  • Has ongoing sensory or motor neuropathy Grade 2 or higher
  • Has active keratitis (superficial punctate keratitis) or corneal ulcerations
  • Has a history of uncontrolled diabetes defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to <8% with associated diabetes symptoms
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The safety and efficacy of these investigational compounds, or investigational uses of marketed products, have not been established. For an agent(s) whose safety and efficacy have not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Learn how to refer your patients for the EV-304 study.

Reference: 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) (KEYNOTE-B15) (01-07-2021). Accessed 04-18-2022.