Study

Overview

Official Title: A Phase 3, Randomized, Open-label Study to Evaluate Perioperative Enfortumab Vedotin Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Gemcitabine and Cisplatin in Cisplatin-eligible Participants with Muscle-invasive Bladder Cancer (KEYNOTE-B15 / EV-304)

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).

Study Type:

Interventional

Study Phase:

Phase 3

Estimated Enrollment:

784

Study Start Date:

April 2021

Estimated Study Completion Date:

December 2026

Estimated Primary Completion Date:

December 2026

Eligibility

Ages Eligible for Study:

18 years and older

Genders Eligible for Study:

All

Accepts Healthy Volunteers:

No

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

Study Detail

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)

Overview

Eligibility

CRITERIA

Locations

Results

Plain Language Summaries