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)

ID#: NCT04700124

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 3

Recruitment Status: Recruiting

Start Date: April 21, 2021

End Date: June 23, 2026

Contact Information:
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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).
Eligibility:

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
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