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)

• Status: Recruiting
• Trial end date: 2026-06-23
• Target enrollment: 0
• Participant gender: All

Summary

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 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).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Collaborators: Astellas Pharma Inc; Seagen Inc.
• Treatments: Cisplatin; Gemcitabine; Pembrolizumab

Criteria

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 (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis

• Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND)

• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Have adequate organ function

Exclusion Criteria:

• Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions

• Has received any prior systemic treatment for MIBC or non-invasive muscle 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

• Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol

• 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 allogenic 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